building blocks: Applications in carbohydrate synthesis with the … · 2019. 10. 14. · building...
Transcript of building blocks: Applications in carbohydrate synthesis with the … · 2019. 10. 14. · building...
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Supporting information
Synthesis of photolabile protecting group (PPG) protected uronic acid
building blocks: Applications in carbohydrate synthesis with the
assistance of continuous flow photoreactor
Varsha Tiwari,a# Adesh Kumar Singh,a# Priyanka Chaudhary,a Peter H. Seeberger,b
Jeyakumar Kandasamya*
aDepartment of Chemistry, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh-
221005, India. E-mail: [email protected] bMax-Planck-Institute of Colloids and Interfaces, Department of Biomolecular Systems,
Am Mühlenberg 1, 14476 Potsdam, Germany
# These authors contributed equally to this work
Table of Contents
S.No. Content Page No.
1 General information 2
2 (a)-General procedure for synthesis of uronic acid esters with 2-
nitrobenzyl bromide (1a-1o)
(b)- General procedure for synthesis of uronic acid esters (1m-
1n):
2-5
3 Analytical data of 2-nitrobenzyl protected uronic acid esters(1a-
1o and 4a-4d)
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4 Experimental procedure for deprotection of photolabile 2-
nitrobenzyl protecting group by using a continuous flow
photoreactor
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5 Analytical data for various deprotected uronic acids (2a-2o) 13- 18
6 Procedure for synthesis of D-Glucopyranuronic acid, 2,3,4-tris-O-
(phenylmethyl)-,2-nitrophenylmethylester,1-(2,2,2-
trichloroethanimidate) (1aa).
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7 General procedure for glycosylation 19
8 Analytical data for various deprotected uronic acids (5a-5d) 19-21
10 Copy of 1H and 3C-NMR spectra of intermediates and final
compounds
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Electronic Supplementary Material (ESI) for Organic Chemistry Frontiers.This journal is © the Partner Organisations 2019
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1. General Information
Starting materials were prepared using literature procedures or modified procedures. Solvents
and chemicals were purchased from commercial sources and used without further
purification. Thin layer chromatography was performed using pre-coated plates contained
from E. Merck (TLC silica gel 60 F254). TLC plates were visualized by exposure to
ultraviolet light (UV), and then further analyzed by charring in stain solution (5% H2SO4 in
MeOH). The column chromatography was performed on silica gel (100-200 mesh) using a
mixture of ethyl acetate/hexane and methanol/ethyl acetate as an eluent. The Continuous
Flow Photoreactor was constructed with the help of M/s Lelesil innovative systems, Mumbai,
India. The NMR spectra were recorded on BrukerAvance 500 MHz NMR spectrometer and
Mass spectra were measured on Water’s Quattro Micro V 4.1. All given 13C spectra are
proton decoupled. The 1H NMR and 13C NMRs of the monosaccharide primary alcohol and
corresponding uronic acids were compared with literature reports.
2 (a)- General procedure for synthesis of uronic acid esters with 2-nitrobenzyl bromide:
(1a-1o)
To a stirred solution of appropriate uronicacid (0.5 equiv.) in dry DMF, KHCO3(4.0 equiv.),
Bu4NI (0.2 equiv.) and 2-nitrobenzyl bromide (3 equiv.) were added under argon atmosphere.
The resulting mixture was stirred for 16 h at room temperature. After completion, the reaction
mixture was filtered on celite. The filtrate was washed with water (2×50 mL) and dried over
anhydrous sodium sulfate. The solvent was concentrated under reduced pressure to provide
crude product which was purified by column chromatography on silica gel of 100-200 mesh
size. Ethyl acetate/hexane was used as an eluent.
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(b)- Preparation of uronic acid esters 1m and 1n:
1m preparation: The compound AA (3.0 g, 8.0 mmol) was stirred in dry pyridine (20 mL) in
the presence of tert-butyldimethylsilyl chloride (1.81 g, 12.0 mmol) for overnight at room
temperature. After completion, the reaction mixture was evaporated till dryness and dissolved
in ethyl acetate. The resulting solution was washed with 0.1N HCl solution and brine
solution. The crude was subjected for the column chromatography on silica (30% EtOAc:
Hexane) to afford the primary TBDMS protected compound as a colorless syrup (3.13 g, 80%
yield).
The TBDMS protected compound (1.0 g, 2.0 mmol) was dissolved in DMF (20 ml) at 0oC to
which NaH (98 mg, 2 equiv.) followed by 4-bromobenzylbromide (562 mg, 1.1 eq.) was
added. The reaction was stirred until TLC starting material got consumed. The reaction was
quenched using water (5 mL) and diluted with ethyl acetate (20 mL). The ethyl acetate layer
was washed with cold water and evaporated in vacuo. The crude product was further dried
under high vacuum and dissolved in THF (20 ml) to which TBAF (3.0 equiv.) was added and
stirred until starting material disappeared. The solvent was evaporated and the residue was
dissolved in ethyl acetate and washed with brine. The organic layer was evaporated in vacuo
and purified using column chromatography (20% EtOAc: Hexane) to afford the pure
compound AB (723 mg, 70%) as yellowish oil.
To a vigorously stirred solution of AB (700 mg, 1.3 mmol) in DCM and H2O was added
TEMPO (0.3 eq) and 1-chloro-1, 2-benziodoxol-3(1H)-one (CBI) (909 mg, 2.5 eq). Stirring
was allowed until TLC indicated complete conversion of the starting material to a lower
running spot (~ 45 min). The reaction mixture was quenched by the addition of 10 ml
Na2S2O3 solution (10% in H2O). The mixture was then extracted twice with EtOAc (10 ml)
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and the combined organic layers were dried (Na2SO4), filtered and concentrated. The crude
compound was purified by column chromatography using EtOAc/petroleum ether which
afforded the pure glucuronic acid (560 mg, 78%). Further the glucuronic acid (279 mg, 0.5
mmol) was converted into corresponding 2-nitrobenzyl ester 1m by using the general
procedure (2a) mentioned above. The reaction provided 1m as pale yellow viscous liquid
(325 mg, 94%).
1n preparation: The same procedure was adopted as above described for the preparation of
1m. In the place of 4-bromobenzylbromide, 2-napthylmethylbromide (497mg, 1.1 eq.) was
used. The compound AC was obtained as yellowish oil (736 mg, 75%). Corresponding
glucuronic acid was obtained as pale yellow viscous compound (532 mg, 74%). The ester 1n
was obtained as pale yellow viscous liquid (309 mg, 93%).
((2R,3R,4S,5R,6R)-4,5-bis(benzyloxy)-3-((4-bromobenzyl)oxy)-6-methoxytetrahydro-2H-
pyran-2-yl)methanol (AB):
Yellowish oil (667 mg, 60%); Rf value =0.4 in 20% EtOAc/
Hexane.IR: νmax(neat) 3320, 1099, 652 cm-1.[α]D
24= +45.0 [c 0.1,
CHCl3];1H NMR (500 MHz, CDCl3) δ 7.40 (dd, J = 8.6, 1.9 Hz,
2H), 7.35–7.26 (m, 10H), 7.11 (d, J = 8.4 Hz, 2H), 4.98 (d, J = 11.0
Hz, 1H), 4.83–4.73 (m, 3H), 4.64 (d, J = 12.1 Hz, 1H), 4.57 (dd, J =
7.4, 3.9 Hz, 2H), 3.98 (t, J = 9.3 Hz, 1H), 3.76 (dd, J = 11.7, 2.4 Hz,
1H), 3.69–3.62 (m, 2H), 3.52–3.47 (m, 2H), 3.35 (s, 3H), 1.95 (s,
1H). 13C NMR (125 MHz, CDCl3) δ 138.8, 138.1, 137.3, 131.6,
129.5, 128.6, 128.5, 128.2, 128.0, 127.9, 127.7, 121.7, 98.2, 81.9,
80.1, 77.6, 75.8, 74.2, 73.4, 70.8, 61.8, 55.3. HRMS: Calc. for
C28H36BrO6[M+H]+: 543.1382, Obser. 543.1383
((2R,3R,4S,5R,6R)-4,5-bis(benzyloxy)-6-methoxy-3-(naphthalen-2-ylmethoxy)tetrahydro-
2H-pyran-2-yl)methanol (AC):
Yellowish oil (685 mg, 65 %); Rfvalue =0.4 in 20% EtOAc/
Hexane.IR: νmax(neat) 3233, 1052, 631 cm-1.[α]D
24= +25.0 [c 0.1,
CHCl3];1H NMR (500 MHz, CDCl3) δ 7.79–7.74 (m, 3H), 7.69 (s,
1H), 7.45–7.41 (m, 2H), 7.39 (dd, J = 8.4, 1.6 Hz, 1H), 7.36–7.24 (m,
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10H), 5.01 (dd, J = 11.1, 6.6 Hz, 2H), 4.85 (d, J = 11.0 Hz, 1H), 4.79
(dd, J = 11.7, 7.1 Hz, 2H), 4.65 (d, J = 12.1 Hz, 1H), 4.57 (d, J = 3.6
Hz, 1H), 4.04 (t, J = 9.3 Hz, 1H), 3.78 (dd, J = 11.5, 2.3 Hz, 1H),
3.72–3.66 (m, 2H), 3.58 (t, J = 9.3 Hz, 1H), 3.51 (dd, J = 9.6, 3.6 Hz,
1H), 3.35 (s, 3H), 1.89 (s, 1H). 13C NMR (125 MHz, CDCl3) δ 138.9,
138.2, 135.7, 133.4, 133.1, 128.6, 128.5, 128.3, 128.2, 128.1, 127.8,
127.7, 126.8, 126.26, 126.0, 126.0, 98.3, 82.1, 80.1, 77.6, 75.8, 75.2,
73.5, 70.9, 62.0, 55.3. HRMS: Calc. for C32H34O6 [M+H]+: 515.2434,
Obser. 515.2436
3. Analytical data of 2-nitrobenzyl protected uronic acid esters:
α-D-Glucopyranosiduronic acid, methyl-2,3,4-tris-O-(phenylmethyl)-2-nitrophenylmethyl
ester(1a)
Pale yellow viscous liquid (289 mg, 94%), Rfvalue =0.7 in 30% EtOAc/
Hexane. IR: νmax(neat) 1742, 1425, 1120, 1090 cm-1. [α]D
24= -21.7 [c 0.1,
CHCl3];1H NMR (500 MHz, CDCl3) δ 8.12 (dd, J = 5.9, 3.6 Hz, 1H), 7.53 (dd,
J = 5.7, 3.5 Hz, 1H), 7.47–7.43 (m, 2H), 7.41–7.32 (m, 11H), 7.27 (dd, J = 4.8,
1.7 Hz, 2H), 7.21–7.19 (m, 2H), 5.60–5.53 (m, 2H), 5.02 (d, J = 10.9 Hz, 1H),
4.90–4.84 (m, 3H), 4.69 (t, J = 7.7 Hz, 2H), 4.60 (d, J = 11.0 Hz, 1H), 4.34 (d,
J = 10.0 Hz, 1H), 4.07 (t, J = 9.3 Hz, 1H), 3.84 (t, J = 9.5 Hz, 1H), 3.64 (dd, J
= 9.6, 3.5 Hz, 1H), 3.47 (s, 3H).13C NMR (125 MHz, CDCl3) δ 169.1, 147.1,
138.4, 137.9, 133.9, 131.5, 128.7, 128.6, 128.5, 128.4, 128.4, 128.3, 128.2,
128.1, 128.0, 127.7, 127.7, 125.0, 98.8, 81.5, 79.4, 79.3, 75.9, 75.0, 73.6, 70.3,
63.7, 55.7. HRMS: Calc. for C35H36NO9[M+H]+:614.2390, Obser.614.2397.
α-D-Glucopyranosiduronic acid, methyl-2,3,4-tri-O-benzoyl-2-nitrophenylmethyl ester(1b)
Pale yellow viscous liquid (304 mg, 91%); Rfvalue =0.4 in 30% EtOAc/
Hexane.IR: νmax(neat) 1750, 1719, 1420, 1099 cm-1.[α]D
24= +93.0 [c 0.1,
CHCl3];1H NMR (500 MHz, CDCl3) δ 8.16–8.10 (m, 2H), 8.00 (dd, J = 17.6,
9.4 Hz, 3H), 7.77 (d, J = 7.7 Hz, 1H), 7.70 (dd, J= 11.9, 5.7 Hz, 2H), 7.62–7.33
(m, 11H), 5.86 (t, J = 9.6 Hz, 1H), 5.73 (d, J = 6.8 Hz, 1H), 5.51–5.41 (m, 1H),
5.26 (tdd, J = 42.0, 9.9, 3.6 Hz, 2H), 5.00 (s, 1H), 4.60 (d, J = 10.1 Hz, 1H),
4.49 (d, J = 9.8 Hz, 1H), 4.22 (td, J = 9.5, 2.7 Hz, 1H), 3.52 (s, 3H).13C NMR
(125 MHz, CDCl3) δ 169.0, 167.5, 166.8, 165.9, 147.4, 136.8, 134.1, 134.0,
133.6, 133.5, 133.4, 133.4, 131.3, 129.9, 129.9, 129.8, 129.4, 129.2, 129.0,
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129.0, 128.9, 128.9, 128.4, 128.4, 128.4, 127.9, 125.2, 125.0, 97.5, 72.6, 71.0,
70.6, 64.1, 62.5, 56.0. HRMS: Calc. for C35H30NO12[M+H]+: 656.1768, Obser.
656.1772.
α-D-Glucopyranosiduronic acid, methyl 2, 3-di-O-acetyl-4-O-benzyl-2-nitrophenylmethyl ester
(1c)
Pale yellow viscous liquid (240 mg, 93%); Rfvalue = 0.36 in 30% EtOAc/
Hexane. IR: νmax(neat) 1745, 1735, 1410, 1215, 1090 cm-1.[α]D
23= +44.5 [c 0.1,
CHCl3];1H NMR (500 MHz, CDCl3) δ 8.15–8.13 (m, 1H), 7.54–7.48 (m, 3H),
7.29–7.27 (m, 4H), 7.20–7.18 (m, 2H), 5.65–5.56 (m, 3H), 5.00 (d, J = 3.5 Hz,
1H), 4.90 (dd, J = 10.2, 3.6 Hz, 1H), 4.59 (s, 2H), 4.40 (d, J = 9.9 Hz, 1H), 3.96
(t, J = 9.6 Hz, 1H), 3.48 (s, 3H), 2.09 (s, 3H), 1.98 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 170.3, 169.7, 168.4, 147.2, 137.3, 133.9, 131.4, 128.8, 128.5, 128.4,
127.9, 127.8, 125.1, 97.4, 77.6, 74.7, 71.3, 70.9, 69.9, 63.9, 55.7, 20.8, 20.7.
HRMS: Calc. for C25H28NO11 [M+H]+: 518.1662, Obser. 518.1668
α-D-Glucopyranosiduronic acid, methyl 2, 3-di-O-benzoyl-4-O-benzyl-2-nitrophenylmethyl
ester (1d)
Yellow viscous liquid (312 mg, 95%); Rf value = 0.42 in 30% EtOAc/ Hexane.
IR: νmax(neat) 1736, 1716, 1290, 1088, 1375 cm-1[α]D
24= +62.9 [c 0.1,
CHCl3];1H NMR (500 MHz, CDCl3) δ 8.16 (dd, J = 8.0, 1.2 Hz, 1H), 8.01–7.98
(m, 4H), 7.60–7.48 (m, 5H), 7.40 (ddd, J = 12.9, 7.5, 5.3 Hz, 4H), 7.16–7.08 (m,
5H), 6.11 (t, J = 9.7 Hz, 1H), 5.65 (q, J = 15.2 Hz, 2H), 5.26–5.21 (m, 2H),
4.63–4.58 (m, 2H), 4.55 (d, J = 9.9 Hz, 1H), 4.21 (t, J = 9.5 Hz, 1H), 3.50 (s,
3H). 13C NMR (125 MHz, CDCl3) δ 168.4, 165.8, 165.4, 147.0, 136.9, 133.9,
133.3, 133.2, 131.4, 129.8, 129.6, 129.3, 128.8, 128.7, 128.4, 128.3, 128.2,
127.9, 127.8, 125.0, 97.5, 77.4, 74.7, 71.8, 71.7, 70.0, 63.8, 55.8. HRMS: Calc.
for C35H32NO11 [M+H]+: 642.1975, Obser. 642.1970
α-D-Mannopyranosiduronic acid, methyl-2, 3, 4-tris-O-(phenylmethyl)-2-nitrophenylmethyl
ester (1e)
Pale yellow viscous liquid (261 mg, 85%); Rf value = 0.5 in 20% EtOAc/ Hexane.
IR: νmax(neat) 1752, 1445, 1135, 1075 cm-1. [α]D
24= +4.7 [c 0.1, CHCl3];1H NMR
(500 MHz, CDCl3) δ 8.11–8.13 (m, 1H), 7.55-7.53 (m, 1H), 7.45–7.22 (m, 18H),
5.54 (q, J = 15.3 Hz, 2H), 4.94 (d, J = 2.9 Hz, 1H), 4.85-4.73 (m, 3H), 4.66-4.60
(m, 3H), 4.36–4.27 (m, 2H), 3.93 (dd, J = 8.1, 3.0 Hz, 1H), 3.80 (t, J = 3.1 Hz,
1H), 3.46 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 168.8, 147.1, 138.2, 138.0,
138.0, 133.8, 131.9, 128.5, 128.5, 128.3, 128.3, 127.8, 127.7, 127.6, 127.6, 125.0,
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99.7, 78.7, 75.6, 74.5, 74.3, 72.9, 72.3, 72.0, 63.5, 55.6. HRMS: Calc. for
C35H36NO9 [M+H]+: 614.2390, Obser. 614.2386
α-D-Mannopyranosiduronic acid, methyl 2, 3, 4-tri-O-benzoyl-2-nitrophenylmethyl ester (1f)
Pale yellow solid (291 mg, 89%); M.P:133-135 ℃; Rf value = 0.6 in 30%
EtOAc/ Hexane. IR: νmax(neat) 1755, 1729, 1414, 1040 cm-1. [α]D
25= -60.2 [c
0.1, CHCl3];1H NMR (500 MHz, CDCl3) δ 8.14–8.08 (m, 4H), 7.99–7.97 (m,
2H), 7.87 (d, J = 8.1 Hz, 2H), 7.63–7.58 (m, 2H), 7.54–7.51 (m, 1H), 7.46–7.37
(m, 7H), 7.30–7.27 (m, 2H), 6.14 (t, J = 10.1 Hz, 1H), 5.95 (dd, J = 10.1, 3.3
Hz, 1H), 5.74 (dd, J = 3.1, 1.7 Hz, 1H), 5.03 (s, 1H), 4.75 (dd, J = 12.1, 2.4 Hz,
1H), 4.54 (dd, J = 12.1, 4.4 Hz, 1H), 4.47–4.39 (m, 1H), 3.57 (s, 3H). 13C NMR
(125 MHz, CDCl3) δ 166.2, 165.5, 165.4, 133.4, 133.4, 133.1, 133.0, 129.8,
129.8, 129.8, 129.7, 129.7, 129.3, 129.1, 129.0, 128.6, 128.47, 128.3, 98.7, 70.4,
70.0, 68.7, 66.9, 62.9, 55.6. HRMS: Calc. for C35H30NO12 [M+H]+: 656.1768,
Obser. 656.1770
β-D-Glucopyranosiduronic acid, phenyl 2, 3, 4-tri-O-benzoyl-1-thio-2-nitrophenylmethyl ester
(1g)
Yellow viscous liquid (338 mg, 92%); Rf value = 0.48 in 30% EtOAc/
Hexane.IR: νmax(neat) 1748, 1718, 1422, 1140 cm-1 .[α]D
24= +18.7 [c 0.1,
CHCl3];1H NMR (500 MHz, CDCl3) δ 8.07 (dd, J = 8.0, 1.5 Hz, 1H), 8.00–
7.98(m, 2H), 7.86–7.82 (m, 4H), 7.58–7.28 (m, 17H), 5.94 (t, J = 9.4 Hz, 1H),
5.73 (t, J = 9.7 Hz, 1H), 5.65–5.51 (m, 3H), 5.11 (d, J = 9.9 Hz, 1H), 4.51 (d, J
= 9.8 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 165.9, 165.6, 165.0, 164.9, 147.2,
133.8, 133.7, 133.4, 133.4, 133.3, 131.0, 130.9, 129.9, 129.8, 129.8, 129.0,
128.8, 128.7, 128.6, 128.5, 128.4, 128.4, 128.3, 125.0, 86.4, 77.2, 76.6, 73.5,
70.0, 69.9, 64.3. HRMS: Calc. for C40H32NO11S [M+H]+: 734.1696, Obser.
734.1699
β-D-Glucopyranosiduronic acid, phenyl-2, 3, 4-tris-O-(phenylmethyl)-1-thio-2-
nitrophenylmethyl ester (1h)
Pale yellow viscous liquid (311 mg, 90%); Rf value = 0.6 in 30% EtOAc/
Hexane. IR: νmax(neat) 1743, 1520, 1145, 1130 cm-1. [α]D
24= -2.9 [c 0.1,
CHCl3];1H NMR (500 MHz, CDCl3) δ 8.18–8.10 (m, 1H), 7.56–7.20 (m,
22H), 5.53 (d, J = 5.3 Hz, 2H), 5.28 (d, J = 3.1 Hz, 1H), 4.94 (d, J = 10.8
Hz, 1H), 4.87–4.80 (m, 3H), 4.71 (d, J = 11.8 Hz, 1H), 4.61 (t, J = 10.4 Hz,
2H), 4.04 (t, J = 9.0 Hz, 1H), 3.84 (t, J = 9.2 Hz, 1H), 3.65 (dd, J = 9.1, 3.3
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Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 169.1, 147.0, 138.2, 137.7, 137.5,
133.9, 131.6, 128.6, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 128.1, 127.9,
127.9, 127.8, 127.7, 125.0, 97.8, 91.7, 80.7, 79.2, 78.9, 75.7, 74.9, 73.5,
70.6, 63.6. HRMS: Calc. for C40H38NO8S [M+H]+: 692.2318, Obser.
692.2315
α-D-galactopyranosiduronic acid- 1, 2, 3, 4-Di-O-isopropylidene-2-nitrophenylmethyl ester (1i)
Pale yellow viscous liquid (180 mg, 88%); Rf value = 0.5 in 30% EtOAc/
Hexane. IR: νmax(neat) 1747, 1465, 1235 cm-1. [α]D
24= -62.4 [c 0.1,
CHCl3];1H NMR (500 MHz, CDCl3) δ 8.13 (d, J = 8.2 Hz, 1H), 7.75 (d, J =
7.8 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.49 (t, J = 7.8 Hz, 1H), 5.75–5.67 (m,
11H), 5.31 (s, 1H), 4.68 (ddd, J = 28.6, 7.7, 2.3 Hz, 2H), 4.56 (d, J = 2.0 Hz,
1H), 4.41 (dd, J = 4.9, 2.6 Hz, 1H), 1.55 (s, 3H), 1.46 (s, 3H), 1.36 (s,
3H).13C NMR (125 MHz, CDCl3) δ 167.8, 147.2, 133.6, 132.0, 129.0, 128.6,
124.9, 110.0, 109.1, 96.5, 72.1, 70.7, 70.2, 68.6, 63.5, 25.9, 25.8, 24.7, 24.6.
HRMS: Calc. for C19H24NO9 [M+H]+: 410.1451, Obser. 410.1448
β-D-Glucopyranosiduronic acid, 4-Methylphenyl-2, 3, 4-tri-O-benzoyl-1-thio-2-nitrophenyl-
methyl ester (1j)
Pale yellow viscous liquid (347 mg, 93%); Rf value = 0.5 in 30% EtOAc/
Hexane.IR:νmax(neat) 1738, 1720, 1255, 1445 cm-1[α]D
24= +10.7 [c 0.1,
CHCl3];1H NMR (500 MHz, CDCl3) δ 8.05 (dd, J = 8.0, 1.4 Hz, 1H),
7.99–7.97 (m, 2H), 7.84–7.80 (m, 4H), 7.52 (dd, J = 10.5, 4.2 Hz, 2H),
7.46–7.38 (m, 8H), 7.32–7.25 (m, 5H), 7.13 (d, J = 7.9 Hz, 2H), 5.93 (t, J
= 9.4 Hz, 1H), 5.69 (t, J = 9.7 Hz, 1H), 5.58 (dd, J = 38.5, 14.8 Hz, 2H),
5.48 (t, J = 9.6 Hz, 1H), 5.04 (d, J = 9.9 Hz, 1H), 4.48 (d, J = 9.8 Hz, 1H),
2.35 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 165.9, 165.6, 165.0, 164.9,
147.2, 139.1, 134.4, 133.7, 133.4, 133.4, 133.3, 131.0, 129.8, 129.8, 129.8,
129.8, 129.1, 129.0, 128.8, 128.6, 128.5, 128.4, 128.4, 128.3, 126.8, 125.0,
86.5, 76.6, 73.5, 70.0, 69.9, 64.2, 21.2. HRMS: Calc. for C41H34NO11S
[M+H]+: 748.1853, Obser. 748.1855
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α-D-Glucopyranosiduronic acid, methyl-2-nitrophenylmethyl ester-2, 3-dibenzoate (1k)
Pale yellow viscous liquid (177 mg, 83%); Rf value = 0.5 in 40% EtOAc/
Hexane. IR: νmax(neat) 3250, 1756, 1718, 1360, 1180, 1080 cm-1[α]D
23=
+134.5 [c 0.1, CHCl3];1H NMR (500 MHz, CDCl3) δ 8.13 (d, J = 8.2 Hz,
1H), 8.00–7.95 (m, 4H), 7.73–7.68 (m, 1H), 7.50 (dd, J = 4.5, 2.9 Hz, 3H),
7.36 (t, J = 7.5 Hz, 5H), 5.89–5.85 (m, 1H), 5.71 (q, J = 15.0 Hz, 2H), 5.25
(s, 2H), 4.49 (d, J = 9.9 Hz, 1H), 4.22 (t, J = 9.6 Hz, 1H), 3.49 (s, 3H), 3.47
(d, J = 0.9 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 168.9, 165.7, 162.5,
147.1, 133.9, 133.3, 133.2, 131.3, 129.7, 129.7, 129.5, 129.1, 128.8, 128.8,
128.7, 128.3, 128.2, 125.0, 97.4, 72.4, 71.0, 70.6, 70.5, 63.9, 55.8. HRMS:
Calc. for C28H26NO11 [M+H]+: 552.1506, Obser. 552.1501
(2S)-2-nitrobenzyl-2-((3aR, 6R, 6aR)-1-benzyl-6-(benzyloxy)-2-oxohexahydrofuro[3, 2-d]oxazol-5-yl)-2-hydroxyacetate (1l)
Pale yellow viscous liquid (214 mg, 80%); Rf value = 0.6 in 50%
EtOAc/ Hexane. IR: νmax(neat) 3355, 1762, 1751, 1290, 1120, 1075 cm-
1. [α]D24= -48.6 [c 0.1, CHCl3];
1H NMR (500 MHz, CDCl3) δ 8.10–
8.09(m, 1H), 7.52–7.45 (m, 3H), 7.41–7.38 (m, 3H), 7.29–7.27 (m,
4H), 7.24–7.22 (m, 2H), 7.12–7.10 (m, 2H), 6.22 (d, J = 5.5 Hz, 1H),
5.61 (dd, J = 80.6, 14.8 Hz, 2H), 4.85 (d, J = 3.6 Hz, 1H), 4.69 (d, J =
15.1 Hz, 1H), 4.32 (s, 2H), 4.20–4.17 (m, 2H), 4.10 (d, J = 5.6 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 166.0, 156.3, 147.3, 136.2, 134.9,
133.8, 131.1, 129.2, 129.1, 129.0, 128.6, 128.6, 128.3, 128.2, 127.6,
125.0, 101.0, 80.0, 79.9, 77.2, 72.4, 63.8, 63.7, 47.6. HRMS: Calc. for
C28H27N2O9 [M+H]+: 535.1717, Obser. 535.1723
(2S,3S,4S,5R,6R)-2-nitrobenzyl-4,5-bis(benzyloxy)-3-(4-bromobenzyloxy)-6-methoxytetra-
hydro-2H-pyran-2-carboxylate (1m)
Pale yellow viscous liquid (325 mg, 94%); Rf value = 0.52 in 20%
EtOAc/ Hexane. IR: νmax(neat)1730, 1520, 1250, 1070, 565 cm-1
[α]D24= -7.8 [c 0.1, CHCl3];
1H NMR (500 MHz, CDCl3) δ 8.17–8.06
(m, 1H), 7.50–7.46 (m, 3H), 7.38–7.28 (m, 12H), 7.02 (d, J = 8.1 Hz,
2H), 5.57 (q, J = 15.0 Hz, 2H), 4.99 (d, J = 10.9 Hz, 1H), 4.83–4.76
(m, 3H), 4.69–4.66 (m, 2H), 4.50 (d, J = 11.3 Hz, 1H), 4.29 (d, J = 10.0
Hz, 1H), 4.02 (t, J = 9.3 Hz, 1H), 3.77 (t, J = 9.5 Hz, 1H), 3.61 (dd, J =
9.6, 3.5 Hz, 1H), 3.46 (s, 3H).13C NMR (125 MHz, CDCl3) δ 169.0,
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10
147.3, 138.4, 137.8, 136.9, 133.7, 131.3, 131.3, 129.2, 128.8, 128.7,
128.5, 128.4, 128.1, 128.1, 127.9, 127.7, 125.1, 121.5, 98.8, 81.3, 79.4,
79.3, 75.8, 74.1, 73.6, 70.1, 63.7, 55.7. HRMS: Calc. for
C35H34BrNO9[M+H]+: 691.1417, Obser.691.1415
(2S,3S,4S,5R,6R)-2-nitrobenzyl-4,5-bis(benzyloxy)-6-methoxy-3-(naphthalen-2-ylmethoxy)-
tetrahydro-2H-pyran-2-carboxylate (1n)
Pale yellow viscous liquid (309 mg, 93%); Rf value = 0.5 in 20%
EtOAc/ Hexane. IR: νmax(neat) 1735, 1515, 1268, 1077 cm-1. [α]D
25=
-8.9 [c 0.1, CHCl3];1H NMR (500 MHz, CDCl3) δ 8.03 (d, J = 7.9
Hz, 1H), 7.79–7.78 (m, 1H), 7.73–7.68 (m, 2H), 7.61 (s, 1H), 7.47–
7.25 (m, 17H), 5.50 (dd, J = 45.3, 15.2 Hz, 2H), 5.03 (dd, J = 11.0,
5.5 Hz, 2H), 4.87 (dd, J = 14.7, 11.6 Hz, 2H), 4.71 (dd, J = 21.0, 8.6
Hz, 3H), 4.36 (d, J = 9.9 Hz, 1H), 4.10 (t, J = 9.2 Hz, 1H), 3.88 (t, J
= 9.5 Hz, 1H), 3.66 (dd, J = 9.6, 3.4 Hz, 1H), 3.47 (s, 3H).13C NMR
(125 MHz, CDCl3) δ 169.0, 147.0, 138.4, 137.9, 135.3, 133.7,
133.1, 132.9, 131.4, 128.5, 128.4, 128.1, 128.1, 128.0, 128.0, 127.8,
127.7, 127.6, 126.4, 126.0, 125.9, 125.7, 124.9, 98.8, 81.5, 79.4,
79.3, 75.9, 75.1, 73.6, 70.3, 63.7, 55.7. HRMS: Calc. for C39H37NO9
[M+H]+: 663.2468, Obser. 663.2471
β-D-Glucopyranosiduronic acid, phenyl-4-O-[6-methyl-2, 3, 4-tris-O-(phenylmethyl)-β-D-
mannopyranuronosyl]-2, 3-bis-O-(phenylmethyl)-1-thio-2-nitrophenylmethyl ester (1o)
Pale yellow viscous liquid (532 mg, 92%); Rf value = 0.5 in 30%
EtOAc/ Hexane. IR: νmax(neat) 1755, 1745, 1395, 1285, 1076 cm-1.
[α]D24= +8.8 [c 0.1, CHCl3];
1H NMR (500 MHz, CDCl3) δ 8.12-7.20
(m, 38H), 5.88 (s, 1H), 5.57 (dd, J = 42.3, 15.3 Hz, 2H), 4.96–4.47
(m, 15H), 4.06 (t, J = 9.3 Hz, 1H), 3.91-3.83 (m, 3H), 3.64–3.61 (m,
2H). 13C NMR (125 MHz, CDCl3) δ 169.7, 168.9, 147.1, 138.5,
138.0, 138.0, 137.1, 137.0, 134.1, 131.7, 128.8, 128.7, 128.7, 128.7,
128.6, 128.5, 128.2, 128.2, 128.0, 128.0, 128.0, 127.9, 127.9, 127.8,
127.8, 125.2, 102.5, 98.9, 81.2, 79.3, 77.4, 75.9, 75.3, 75.3, 74.1,
73.5, 73.0, 73.0, 72.3, 72.2, 71.1, 63.9. HRMS: Calc. for
C67H63N2O16S [M+H]+: 1183.3898, Obser. 1183.3900
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11
β-D-Glucopyranosiduronicacid,hexyl, 2, 3, 4-tri-O-benzyl-2-nitrophenylmethyl ester (4a)
Pale yellow solid (304 mg, 89%); M.P: 96-97 ℃; Rf value = 0.7 in
30% EtOAc/ Hexane. β:α isomer (>20:1); IR: νmax(neat) 1751, 1517,
1305, 1125 cm-1. [α]D24= -9.6 [c 0.1, CHCl3];
1H NMR (500 MHz,
CDCl3) δ 8.15–8.13 (m, 1H), 7.58–7.56 (m, 1H), 7.49–7.45 (m, 2H),
7.39–7.30 (m, 10H), 7.29–7.25 (m, 3H), 7.19 (dd, J = 6.8, 2.8 Hz,
2H), 5.63 (d, J = 15.3 Hz, 1H), 5.53 (d, J = 15.2 Hz, 1H), 4.97 (dd, J
= 10.8, 9.6 Hz, 2H), 4.85 (dd, J = 16.8, 11.0 Hz, 2H), 4.76 (d, J =
10.9 Hz, 1H), 4.61 (d, J = 11.0 Hz, 1H), 4.53 (d, J = 7.7 Hz, 1H),
4.04–3.96 (m, 2H), 3.92 (t, J = 9.4 Hz, 1H), 3.73 (t, J = 9.1 Hz, 1H),
3.61-3.53 (m, 2H), 1.71–1.66 (m, 3H), 1.45–1.29 (m, 7H), 0.92 (dd,
J = 9.5, 4.6 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 167.9, 147.1,
138.3, 138.2, 137.8, 133.8, 131.7, 128.6, 128.5, 128.4, 128.3, 128.1,
127.9, 127.8, 127.8, 127.7, 127.7, 125.0, 104.0, 83.9, 81.7, 78.9,
75.7, 74.9, 74.8, 74.5, 70.5, 63.6, 31.6, 29.6, 25.8, 22.5, 14.0.
HRMS: Calc. for C40H46NO9 [M+H]+: 684.3173, Obser. 684.3168
β-D-Glucopyranosiduronic acid-1, 2, 3, 4-tetra-O-benzyl-2-nitrophenylmethyl ester (4b)
OBnOBnO
OBn
O
ONO2
OBn
4b
Pale yellow powder. (293 mg, 85%); M.P: 124-126 ℃; Rf value = 0.72 in 30%
EtOAc/ Hexane. β:α isomer (>20:1); IR: νmax(neat) 1775, 1480, 1310, 1095
cm-1. [α]D24= -22.9 [c 0.1, CHCl3];
1H NMR (500 MHz, CDCl3) δ 8.15–8.13(m,
1H), 7.59–7.57 (m, 1H), 7.48–7.45 (m, 2H), 7.41–7.26 (m, 19H), 7.21–7.18
(m, 2H), 5.59 (dd, J = 49.7, 15.2 Hz, 2H), 5.02–4.93 (m, 3H), 4.84 (dd, J =
21.8, 11.0 Hz, 2H), 4.73 (dd, J = 22.2, 11.3 Hz, 2H), 4.64 (dd, J = 13.2, 9.3
Hz, 2H), 4.05 (d, J = 9.7 Hz, 1H), 3.96–3.93 (m, 1H), 3.74 (t, J = 9.0 Hz, 1H),
3.63 (dd, J = 9.0, 7.6 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 167.9, 147.2,
138.2, 138.1, 137.8, 137.0, 133.8, 131.6, 128.7, 128.6, 128.5, 128.4, 128.4,
128.4, 128.3, 128.1, 128.0, 127.9, 127.9, 127.8, 127.8, 127.7, 127.7, 125.0,
102.8, 83.9, 81.8, 78.9, 75.7, 74.9, 74.6, 71.4, 63.7. HRMS: Calc. for
C41H40NO9 [M+H]+: 690.2703, Obser. 690.2702
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12
α-D-Glucopyranoside,methyl-6-O-[6-methyl-2,3,4-tris-O-(phenylmethyl)-D-glucopyranurono-
syl]-2, 3, 4-tris-O-(phenylmethyl)-2-nitrophenylmethyl ester (4c)
Yellow solid (408 mg, 78%); M.P: 103-105 ℃; Rf value = 0.5 in 30%
EtOAc/ Hexane. β:α isomer (3:2); IR: νmax(neat) 1762, 1487, 1254,
1082 cm-1. [α]D24= +12.1 [c 0.1, CHCl3];
1H NMR (500 MHz, CDCl3)
δ 8.12–8.09 (m, 1H), 7.45–7.39 (m, 2H), 7.38–7.24 (m, 29H), 7.18
(ddd, J = 7.7, 6.7, 1.7 Hz, 3H), 5.62–5.43(m, 2H), 5.03–4.92 (m, 3H),
4.88–4.52 (m, 10H), 4.44 (t, J = 8.8 Hz, 1H), 4.17 (dd, J = 10.8, 1.7
Hz, 1H), 4.04–3.97 (m, 2H), 3.91–3.78 (m, 3H), 3.71–3.46 (m, 4H),
3.37 (d, J = 29.8 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 169.2,
167.7, 147.1, 138.8, 138.4, 138.3, 138.3, 138.2, 138.1, 138.1, 138.0,
137.8, 133.8, 133.7, 131.6, 131.6, 128.6, 128.5, 128.5, 128.4, 128.4,
128.4, 128.3, 128.2, 128.1, 128.0, 128.0, 127.9, 127.9, 127.9, 127.8,
127.7, 127.7, 127.7, 127.6, 127.6, 127.6, 127.5, 127.5, 125.0, 124.9,
104.1, 98.0, 98.0, 97.8, 84.0, 82.1, 81.9, 81.5, 81.0, 80.1, 79.8, 79.5,
79.3, 78.8, 77.9, 77.7, 77.2, 75.7, 75.7, 75.6, 75.0, 74.9, 74.9, 74.8,
74.6, 73.3, 72.7, 70.4, 70.3, 69.8, 68.9, 66.7, 63.6, 63.5, 55.2. HRMS:
Calc. for C62H64NO14 [M+H]+: 1046.4327, Obser. 1046.4329
D-Glucopyranosiduronic acid-1, 2, 3, 4-tetra-O-benzyl-2-nitrophenylmethyl ester (4d)
White solid. (165 mg, 52%); M.P: 123-125 ℃;Rf value = 0.5 in 20% EtOAc/
Hexane. β:α isomer (3:1); IR: νmax(neat) 1775, 1480, 1310, 1095 cm-1.
[α]D24= -9.9 [c 0.1, CHCl3];
1H NMR (500 MHz, CDCl3) δ 8.15–8.14 (m,
1H), 7.60–7.20 (m, 24H), 5.66–5.53 (m, 2H), 5.03–4.95 (m, 3H), 4.89–4.71
(m, 4H), 4.65 (dd, J = 12.6, 9.4 Hz, 2H), 4.07 (d, J = 9.7 Hz, 1H), 3.97 (t, J =
9.3 Hz, 1H), 3.75 (t, J = 9.0 Hz, 1H), 3.65–3.62 (m, 1H).13C NMR (125
MHz, CDCl3) δ 169.1, 168.0, 147.2, 138.5, 138.3, 138.1, 137.9, 137.8, 137.0,
136.7, 133.8, 131.6, 128.7, 128.7, 128.6, 128.6, 128.5, 128.4, 128.4, 128.4,
128.3, 128.3, 128.2, 128.1, 128.0, 128.0, 127.9, 127.8, 127.8, 127.8, 127.7,
125.1, 102.8, 96.1, 83.9, 81.8, 81.5, 79.4, 79.4, 78.9, 75.9, 75.7, 75.1, 74.9,
74.6, 73.2, 71.4, 70.6, 69.6, 63.7. Calc. for C41H40NO9 [M+H]+: 690.2703,
Obser. 690.2705
-
13
4. Experimental procedure for deprotection of photolabile 2-nitrobenzyl protecting
group by using a continuous flow photoreactor:
Approximately 0.005M solution of photolabile protected uronic acid building blocks were
prepared in methanol and added to the reactor B. The solution was circulated with the help of
peristaltic pump to the flexi coil with a flow rate 50 RPM which required approx. 3 minutes
for completing one cycle. Total six cycles were repeated after which the solvent was
evaporated and purified through column chromatography.
5. Analytical data for various deprotected uronic acids:
Methyl-2, 3, 4-tri-O-benzyl-α-D-glucopyranosiduronic acid (2a)1
Colourless oily syrup (110mg, 92%); Rfvalue =0.6 in 50% EtOAc/ Hexane.
IR:νmax(neat) 3482, 1712, 1120 cm-1. [α]D
24= +4.4 [c 0.1, CHCl3]; 1H NMR
(500 MHz, DMSO-D6) δ 7.40–7.22 (m, 16H), 4.91 (d, J = 3.4 Hz, 1H), 4.84
(d, J = 11.3 Hz, 1H), 4.75–4.66 (m, 4H), 4.58 (d, J = 11.0 Hz, 1H), 3.93 (d,
J = 9.9 Hz, 1H), 3.79 (t, J = 9.3 Hz, 1H), 3.66–3.62 (m, 1H), 3.56 (dd, J =
9.6, 3.4 Hz, 1H), 3.34 (s, 3H).13C NMR (125 MHz, DMSO-D6) δ 170.9,
139.0, 138.8, 138.6, 128.7, 128.6, 128.6, 128.1, 128.1, 128.0, 127.9, 127.9,
127.8, 127.8, 98.0, 80.8, 79.6, 75.0, 74.5, 72.0, 70.4, 55.3.HRMS: Calc. for
C28H31O7[M+H]+: 479.2070, Obser.479.2075.
Methyl-2, 3, 4-tri-O-benzoyl-α-D-glucopyranosiduronic acid (2b)
Colourless Oily syrup (116 mg, 89%);Rfvalue =0.5 in 60% EtOAc/ Hexane.
IR: νmax(neat) 3545, 1718, 1710 cm-1. [α]D
24= +62.2 [c 0.1, CHCl3];1H NMR
(500 MHz, CDCl3) δ 8.00–7.89 (m, 6H), 7.53 (q, J = 7.6 Hz, 2H), 7.46 (t, J
= 7.4 Hz, 1H), 7.41-7.36 (m, 4H), 7.32 (t, J = 7.8 Hz, 2H), 6.20 (t, J = 9.8
Hz, 1H), 5.75 (t, J = 9.8 Hz, 1H), 5.37 (d, J = 3.6 Hz, 1H), 5.33 (dd, J =
10.1, 3.6 Hz, 1H), 4.66 (d, J = 10.1 Hz, 1H), 3.54 (s, 3H).13C NMR (125
MHz, CDCl3) δ 171.1, 165.7, 165.6, 165.4, 133.4, 133.4, 133.2, 129.9,
129.9, 129.7, 129.0, 128.8, 128.4, 128.4, 128.3, 97.4, 77.2, 71.4, 69.8, 68.0,
56.3.HRMS: Calc. for C28H25O10[M+H]+: 521.1448, Obser. 521.1446
Methyl-2, 3-di-O-acetyl-4-benzyl-α-D-glucopyranosiduronic acid (2c)
Colourless oily syrup (87mg, 91 %); Rfvalue =0.5 in 50% EtOAc/Hexane. IR:
νmax(neat) 3353, 1735, 1719, 1082 cm-1. [α]D
24= +53.6 [c 0.1, CHCl3];1H
NMR (500 MHz, CDCl3) δ 7.34–7.29 (m, 7H), 7.26–7.25 (m, 2H), 5.59–5.55
(m, 1H), 4.99 (d, J = 3.5 Hz, 1H), 4.88 (dd, J = 10.2, 3.6 Hz, 1H), 4.65 (dd, J
-
14
= 54.8, 11.1 Hz, 3H), 4.33 (d, J = 9.9 Hz, 1H), 3.89 (t, J = 9.5 Hz, 1H), 3.46
(s, 3H), 2.09 (s, 3H), 1.97 (s, 3H).13C NMR (125 MHz, CDCl3) δ 172.2,
170.3, 169.7, 137.2, 128.4, 128.0, 128.0, 97.3, 77.5, 74.7, 71.3, 70.8, 69.4,
55.8, 20.7, 20.7. HRMS: Calc. for C18H23O9[M+H]+: 383.1342, Obser.
383.1343
Methyl-2, 3-di-O-benzoyl-4-benzyl-α-D-glucopyranosiduronic acid (2d)
Colourless oily liquid (119 mg, 94%);Rfvalue =0.6 in 50% EtOAc/ Hexane.
IR: νmax(neat) 3260, 1715, 1708, 1124 cm-1. [α]D
24= +108.1 [c 0.1, CHCl3];1H
NMR (500 MHz, CDCl3) δ 8.10–8.08 (m, 4H), 7.62 (dd, J = 15.5, 7.5 Hz,
2H), 7.49 (dt, J = 15.8, 7.9 Hz, 4H), 7.26 (s, 5H), 6.20 (t, J = 9.6 Hz, 1H),
5.35 (dt, J = 10.0, 3.6 Hz, 2H), 4.77 (dd, J = 38.0, 10.9 Hz, 2H), 4.61 (d, J =
9.9 Hz, 1H), 4.28 (t, J= 9.5 Hz, 1H), 3.58 (s, 3H).13C NMR (125 MHz,
CDCl3) δ 173.6, 166.0, 165.6, 136.9, 133.5, 133.3, 129.9, 129.7, 129.4, 128.8,
128.4, 128.3, 128.2, 128.0, 97.5, 77.4, 77.3, 77.1, 76.9, 74.8, 71.9, 71.7, 69.8,
55.9.HRMS:Calc. for C28H27O9[M+H]+: 507.1650, Obser.507.1648
Methyl-2, 3, 4-tri-O-benzyl-α-D-mannopyranosiduronic acid (2e)1
Colourless oily syrup (105 mg, 88 %); Rfvalue =0.5 in50% EtOAc/PE;
IR:νmax (neat) 3386, 1725, 1135 cm-1.[α]D
23=+15.0 (c, 1.2 in CHCl3); 1H
NMR (500 MHz, CDCl3) δ 7.39–7.28 (m, 15H), 4.96 (s, 1H), 4.76 (dt, J =
24.4, 11.2 Hz, 4H), 4.64 (d, J = 3.9 Hz, 2H), 4.31–4.21 (m, 2H), 3.93–3.91
(m, 1H), 3.80–3.79 (m, 1H), 3.46 (d, J = 1.3 Hz, 3H).13C NMR (125 MHz,
CDCl3) δ 174.1, 138.1, 138.0, 137.7, 128.4, 128.1, 127.9, 127.8, 127.7, 127.7,
127.6, 99.6, 78.5, 75.6, 74.5, 72.9, 72.4, 71.3, 55.7.HRMS: Calc. for
C28H30O7Na [M+Na]+: 501.1890, Obser.501.1893.
Methyl-2, 3, 4-tri-O-benzoyl-α-D-mannopyranosiduronic acid (2f)
Colorless oily syrup (121 mg, 93 %); Rf value =0.4 in 50% EtOAc/PE; IR:
νmax(neat) 3558, 1712, 1708 cm-1. [α]D
24= -61.4 [c 0.1, CHCl3];1H NMR (500
MHz, CDCl3) δ 8.10 (dd, J = 8.2, 1.2 Hz, 2H), 7.98–7.97 (m, 2H), 7.87 (dd, J =
8.3, 1.2 Hz, 2H), 7.62 (t, J= 7.4 Hz, 1H), 7.54–7.45 (m, 4H), 7.39 (t, J = 7.7
Hz, 2H), 7.31 (t, J = 7.8 Hz, 2H), 6.05 (t, J = 9.5 Hz, 1H), 5.92 (dd, J = 9.6, 3.4
Hz, 1H), 5.69 (dd, J = 3.2, 2.5 Hz, 1H), 5.16 (d, J = 2.2 Hz, 1H), 4.69 (d, J =
9.4 Hz, 1H), 3.59 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 171.4, 165.5, 165.4,
165.3, 133.6, 133.4, 133.3, 129.9, 129.8, 129.7, 129.1, 129.0, 128.9, 128.6,
-
15
128.4, 128.3, 98.8, 69.8, 69.4, 69.3, 67.4, 56.2. HRMS: Calc. for C28H25O10
[M+H]+β: 521.1448, Obser. 521.1455
Phenyl-2, 3, 4-tri-O-benzoyl-1-thio-β-D-glucopyranosyduronic acid (2g)
Colorless oily syrup (133 mg, 89%); Rf value = 0.53 in 50% EtOAc/PE; IR:
νmax(neat) 3440, 1712, 1705 cm-1. [α]D
24= +23.3 [c 0.1, CHCl3];1H NMR
(500 MHz, CDCl3) δ 7.99–7.97 (m, 2H), 7.92–7.91 (m, 2H), 7.84–7.83 (m,
2H), 7.56–7.28 (m, 14H), 5.92 (t, J = 9.3 Hz, 1H), 5.73 (t, J = 9.6 Hz, 1H),
5.54 (t, J = 9.6 Hz, 1H), 5.11 (d, J = 9.9 Hz, 1H), 4.39 (d, J = 9.8 Hz, 1H).
13C NMR (125 MHz, CDCl3) δ170.4, 165.6, 165.1, 164.9, 133.3, 133.3,
133.2, 131.7, 129.9, 129.8, 129.8, 129.2, 129.0, 129.0, 128.8, 128.4, 128.4,
128.3, 128.2, 86.5, 73.8, 70.3, 69.9, 66.2. HRMS: Calc. for C33H27O9S
[M+H]+: 599.1376, Obser. 599.1377
Phenyl-2, 3, 4-tri-O-benzyl-1-thio-β-D-glucopyranosyduronic acid (2h)
Colorless oily syrup (132 mg, 95%); Rf value = 0.56 in 50% EtOAc/PE;
IR:νmax (neat) 3280, 1730, 1095 cm-1. [α]D
24= -7.5 [c 0.1, CHCl3];1H NMR
(500 MHz, CDCl3) δ7.60–7.58 (m, 2H), 7.42–7.26 (m, 19H), 4.93 (d, J = 10.3
Hz, 1H), 4.88 (t, J= 7.8 Hz, 2H), 4.81–4.75 (m, 3H), 4.70 (d, J = 10.8 Hz,
1H), 4.01 (d, J = 9.3 Hz, 1H), 3.87 (t, J = 9.0 Hz, 1H), 3.77 (t, J = 8.6 Hz,
1H), 3.58 (dd, J = 9.6, 8.4 Hz, 1H).. 13C NMR (125 MHz, CDCl3) δ 172.3,
138.0, 137.7, 137.3, 133.0, 132.3, 129.1, 128.5, 128.4, 128.4, 128.2, 128.1,
128.0, 127.9, 127.8, 88.1, 85.3, 80.2, 78.7, 77.5, 75.7, 75.4, 75.0. HRMS:
Calc. for C33H33O6S [M+H]+: 557.1998, Obser.557.2001
1, 2, 3, 4-Di-O-isopropylidene-α-D-galactopyranosiduronic acid (2i)
Colorless viscous liquid (62 mg, 90%); Rf value = 0.6 in 50% EtOAc/
Hexane.IR:νmax (neat) 3315, 1715 cm-1.1H NMR (500 MHz, DMSO-d6) δ 5.53
(d, J = 5.0 Hz, 1H), 4.65 (dd, J = 7.7, 2.5 Hz, 1H), 4.51 (dd, J = 7.7, 2.3 Hz, 1H),
4.40 (dd, J = 5.0, 2.5 Hz, 1H), 4.18 (d, J = 2.2 Hz, 1H), 1.43 (s, 3H), 1.32 (s,
3H), 1.28 (d, J = 3.3 Hz, 6H). 13C NMR (125 MHz, DMSO-d6) δ 169.3, 109.1,
108.5, 96.2, 71.9, 70.5, 69.9, 67.7, 26.2, 26.1, 25.1, 24.8. HRMS: Calc.
forC12H19O7 [M+H]+: 275.1131, Obser. 275.1129
-
16
Tolyl-2, 3, 4-tri-O-benzoyl-1-thio-β-D-glucopyranosyduronic acid (2j)
White solid (147 mg, 96%); M.P: 195-197 ℃;Rf value = 0.5 in 50%
EtOAc/ Hexane. IR:νmax (neat) 3356, 1727, 1702 cm-1[α]D
24= +12.6 [c
0.1, CHCl3];1H NMR (500 MHz, CDCl3) δ 8.00–7.98 (m, 2H), 7.92 (dd,
J = 8.4, 1.2 Hz, 2H), 7.85–7.83 (m, 2H), 7.57–7.53 (m, 1H), 7.52–7.48
(m, 1H), 7.47–7.45 (m, 3H), 7.43–7.40 (m, 2H), 7.35 (dd, J = 10.8, 4.9
Hz, 2H), 7.31–7.28 (m, 2H), 7.16 (d, J = 7.9 Hz, 2H), 5.93 (t, J = 9.3 Hz,
1H), 5.70 (t, J = 9.6 Hz, 1H), 5.51–5.47 (m, 1H), 5.05 (d, J = 9.9 Hz,
1H), 4.42 (d, J = 9.7 Hz, 1H), 2.37 (s, 3H). 13C NMR (125 MHz, CDCl3)
δ 170.1, 165.7, 165.2, 164.9, 139.1, 134.3, 133.4, 133.4, 133.3, 129.9,
129.9, 129.8, 129.8, 129.1, 128.7, 128.6, 128.4, 128.4, 128.3, 127.0, 86.5,
75.9, 73.5, 70.0, 69.7, 21.2. HRMS: Calc. forC34H29O9S [M+H]+:
613.1532, Obser. 613.1536
Methyl-2, 3-di-O-benzoyl-α-D-glucopyranosiduronic acid (2k)
Colorless oil (94 mg, 90%);Rf value = 0.55 in 50% EtOAc/PE; [α]D24= +4.4 [c
0.1, CHCl3]; IR:νmax (neat) 3520, 3286, 1725, 1718, 1135 cm-1[α]D
24= +151.7
[c 0.1, CHCl3];1H NMR (500 MHz, MeOD-d4) δ 8.00–7.98 (m, 2H), 7.91 (dd,
J = 6.0, 4.7 Hz, 2H), 7.54 (t, J = 7.4 Hz, 2H), 7.42-7.37 (m, 4H), 5.83–5.78
(m, 1H), 5.20 (dd, J = 8.8, 2.7 Hz, 2H), 4.28 (d, J = 10.0 Hz, 1H), 4.09 (t, J =
9.7 Hz, 1H), 3.49 (s, 3H).13C NMR (125 MHz, MeOD-d4) δ 170.9, 166.1,
165.6, 133.2, 132.9, 129.6, 129.3, 129.2, 128.9, 128.1, 128.1, 97.5, 72.5, 71.7,
71.1, 69.8, 54.7. HRMS: Calc. for C21H21O9 [M+H]+: 417.1186,
Obser.416.1190
2-(1-benzyl-6-(benzyloxy)-2-oxohexahydrofuro[3, 2-d]oxazol-5-yl)-2-hydroxyacetic acid (2l)
Colorless oily syrup (54 mg, 79%); Rf value = 0.43 in 60% EtOAc/PE;
IR:νmax (neat) 3306, 3120, 1711, 1302, 1135, 1070 cm-1. [α]D
24= -49.4 [c
0.1, CHCl3];1H NMR (500 MHz, CDCl3) δ 7.37–7.27 (m, 8H), 7.17 (t, J
= 7.4 Hz, 3H), 6.14 (d, J = 5.0 Hz, 1H), 4.73 (s, 1H), 4.65 (d, J = 15.1
Hz, 1H), 4.40–4.31 (m, 2H), 4.17 (d, J = 3.3 Hz, 1H), 4.10 (s, 1H), 4.06–
4.04 (m, 2H). 13C NMR (125 MHz, CDCl3) δ169.3, 156.8, 136.3, 134.7,
129.2, 128.6, 128.6, 128.3, 128.2, 127.8, 101.2, 79.5, 77.4, 77.1, 76.9,
72.6, 64.2, 47.5.HRMS: Calc. for C21H22NO7 [M+H]+: 400.1396, Obser.
400.1395
-
17
(2S,3S,4S,5R,6R)-4,5-bis(benzyloxy)-3-(4-bromobenzyloxy)-6-methoxytetrahydro-2H-pyran-
2-carboxylic acid (2m)
Colorless viscous liquid (124 mg, 89%); Rf value = 0.20 in 50%
EtOAc/PE. IR:νmax (neat) 3263, 1727, 1077, 585 cm-1;[α]D
24= -1.9 [c
0.1, CHCl3];1H NMR (500 MHz, CDCl3) δ 7.40–7.28 (m, 12H), 7.09
(d, J = 8.3 Hz, 2H), 4.99 (d, J = 11.0 Hz, 1H), 4.83–4.74 (m, 3H), 4.66
(t, J = 7.3 Hz, 2H), 4.58 (d, J = 11.1 Hz, 1H), 4.24 (d, J = 10.0 Hz,
1H), 4.02 (t, J = 9.3 Hz, 1H), 3.70 (t, J = 9.5 Hz, 1H), 3.60–3.58 (m,
1H), 3.44 (s, 3H).13C NMR (125 MHz, CDCl3) δ 173.9, 138.3, 137.7,
136.6, 131.4, 129.5, 128.5, 128.4, 128.2, 128.1, 127.9, 127.8, 121.7,
98.6, 81.3, 79.2, 79.1, 75.9, 74.3, 73.6, 69.6, 55.8. HRMS: Calc. for
C28H29BrO7 [M+H]+: 556.1097 , Obser. 556.1094
(2S,3S,4S,5R,6R)-4,5-bis(benzyloxy)-6-methoxy-3-(naphthalen-2-ylmethoxy)tetrahydro-2H-
pyran-2-carboxylic acid (2n)
Colorless viscous liquid (115 mg, 87%); Rfvalue = 0.20 in 50%
EtOAc/PE; IR:νmax (neat) 3215, 1712, 1120 cm-1. [α]D
25= -6.2 [c 0.1,
CHCl3];1H NMR (500 MHz, CDCl3) δ 7.79–7.74 (m, 3H), 7.66 (s,
1H), 7.47–7.44 (m, 2H), 7.39–7.32 (m, 11H), 4.99 (dd, J = 26.3, 10.9
Hz, 2H), 4.86–4.78 (m, 3H), 4.67 (t, J = 7.9 Hz, 2H), 4.29 (d, J = 10.1
Hz, 1H), 4.07 (t, J = 9.3 Hz, 1H), 3.78 (t, J = 9.5 Hz, 1H), 3.62 (dd, J
= 9.6, 3.4 Hz, 1H), 3.44 (s, 3H).13C NMR (125 MHz, CDCl3) δ 173.3,
138.4, 137.8, 134.9, 133.2, 133.0, 128.5, 128.4, 128.2, 128.1, 128.1,
127.9, 127.9, 127.7, 127.6, 126.8, 126.0, 125.9, 125.8, 98.6, 81.4,
79.2, 79.2, 75.9, 75.3, 73.6, 69.6, 55.8. HRMS: Calc. for C32H32O7
[M+H]+: 528.2148, Obser. 528.2150
β-D-Glucopyranosiduronic acid, phenyl-2, 3-di-O-(benzyl)-1-thio-4-O-[2, 3, 4-tri-O-(benzyl)-β-
D-glucopyranosiduronic acid] (2o)
Colorless viscous liquid (207 mg, 91%); Rf value = 0.40 in 60%
EtOAc/PE; IR:νmax (neat) 3540, 3325, 1722, 1710, 1130 cm-1.
[α]D24= +21.0 [c 0.1, CHCl3];
1H NMR (500 MHz, CDCl3) δ
7.38–7.26 (m, 31H), 5.88 (s, 1H), 4.97–4.72 (m, 8H), 4.64–4.57
(m, 4H), 4.49 (t, J = 11.6 Hz, 2H), 4.06 (t, J = 9.3 Hz, 1H), 3.90
(d, J = 16.9 Hz, 2H), 3.80 (t, J = 9.5 Hz, 1H), 3.62 (dd, J = 10.0,
3.8 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 172.8, 169.6,
-
18
6. Procedure for synthesis of D-Glucopyranuronic acid, 2,3,4-tris-O-(phenylmethyl)-,2-
nitrophenylmethyl ester, 1-(2,2,2-trichloroethanimidate) (1aa):
To a stirred solution of thioglycosides,1h (4g, 5.78 mmol) in 40 ml acetone-water (9:1; v/v)
was added N-bromosuccinamide (3.09 g, 17.35 mmol) and stirred for 1hour at room
temperature. After thatthe reaction was quenched with NaHCO3 and evaporated to dryness.
The residue was dissolved in ethyl acetate (150mL) and successively washed with
sat.aq.NaHCO3, water and brine. Organic layer was separated, dried using anhydrous sodium
sulphate, evaporated in vacuo. The resulting residue was purified using silica gel column
chromatography (2:1 hexane/ EtOAc) to give the corresponding hemiacetal2.43 g (70%) as
viscous oil. The hemiacetalwas dissolved in dry CH2Cl2 (20mL) and cooled to 0oC under
argon atmosphere. DBU (0.2 ml,1.33mmol) andtrichloroacetonitrile (3.34 ml, 33.35
mmol)were added slowly and allowed to stir for 2h. After complete consumption of starting
material, the reaction mixture was concentrated in vacuo and purified by silica gel column
chromatography (30% EtOAc/ Hexane) with 1% added Et3N to afford 2.23g (90%) as
colourless foam; α:β isomer (15.31:1); Rf value =0.6 in 20% EtOAc/ Hexane. 1H NMR (500
MHz, CDCl3) δ 8.74 (s, 1H), 8.13 (dd, J = 7.7, 1.7 Hz, 1H), 7.54-7.46 (m, 3H), 7.37–7.33 (m,
10H), 7.30-7.28 (m, 3H), 7.23 (dd, J = 6.6, 3.0 Hz, 2H), 6.61 (d, J = 3.5 Hz, 1H), 5.56 (q, J =
15.3 Hz, 2H), 5.03 (d, J = 10.9 Hz, 1H), 4.91 (t, J = 11.2 Hz, 2H), 4.78 (dd, J = 25.2, 11.7
Hz, 2H), 4.61 (dd, J = 29.5, 10.5 Hz, 2H), 4.16 (t, J = 9.3 Hz, 1H), 3.97–3.87 (m, 2H). 13C
NMR (125 MHz, CDCl3) δ 168.1, 161.0, 147.1, 138.2, 137.6, 137.6, 133.9, 131.4, 128.7,
128.5, 128.5, 128.4, 128.4, 128.1, 128.0, 127.9, 127.9, 127.8, 127.8, 127.7, 125.0, 94.0, 91.0,
80.8, 78.8, 78.5, 75.8, 75.3, 73.1, 72.7, 63.8.
138.4, 137.9, 137.6, 137.0, 136.9, 128.6, 128.6, 128.4, 128.4,
128.2, 128.1, 128.1, 128.0, 127.9, 127.9, 127.7, 127.7, 102.3,
98.4, 81.0, 79.1, 79.0, 77.3, 75.7, 75.2, 75.0, 73.8, 73.4, 72.7,
72.7, 72.2, 72.0, 70.5. HRMS: Calc. for C53H53O12S [M+H]+:
913.3258, Obser. 913.3262
-
19
7. General procedure for Glycosylation:
7.a. Glycosylation through Glycosyl Imidate donor: Donor 1aa(0.5 mmol, 1equiv.) and
acceptor (non- sugar 3 equiv. and sugar 1.2equiv.) were dissolved in freshly dried CH2Cl2
(8ml)and added to a flame dried round bottomed flask containing activated 4Å molecular
sieves (300mg) under argon atmosphere. The reaction mixture was then cooled to 0oC to
which the activator B(C6F5)3 (10mol%) was added. The reaction was stirred further for 1.5 h
allowing temperature to reach room temperature slowly.Quenching was done by the addition
of Et3N and filtered through Celite. The mixture was concentrated in vacuo and the resulting
residue was purified by silica gel column chromatography to afford the desired glycosylated
product (78-89%).
7.b.Glycosylation through thioglycoside donor: Typical NIS/TfOH-promoted
glycosylation procedure: A mixture of glycosyl donor (1h)(0.5 mmol, 1equiv.), glycosyl
acceptor (3 equiv.), and freshly activated molecular sieves (4℃, 300 mg) in CH2Cl2(8.0 mL)
was stirred under argon for 1 h. The solution was cooled to – 78 °C and NIS (1.1equiv.) and
TfOH (10mol %) were added. The reaction was slowly allowed to reach 0 °C. Upon
completion, the reaction was quenched by adding Et3N. The solid was filtered off and the
filtrate was washed with 1 M HCl, sat. NaHCO3 solution, 10% Na2S2O3and brine. The
organic layer was separated, dried with anhydrous Na2SO4, and concentrated in vacuo. The
residue was purified by flash column chromatography on silica gel to afford the
corresponding glycoside with 52% yield.
8. Analytical data for various deprotected uronic acids:
n-Hexyl-2, 3, 4-tri-O-benzyl-D-glucopyranosiduronic acid (5a)
White foam (123 mg, 90%);Rfvalue =0.5 in 50% EtOAc/
Hexane. IR:νmax (neat) 3105, 1716, 1132 cm-1; β:α isomer
(>20:1);[α]D24= -6.4 [c 0.1, CHCl3];
1H NMR (500 MHz, CDCl3)
δ 7.38–7.25 (m, 16H), 4.94 (dd, J = 17.6, 11.0 Hz, 2H), 4.81 (d,
J = 10.2 Hz, 2H), 4.75 (d, J = 11.0 Hz, 1H), 4.67 (d, J = 10.7
Hz, 1H), 4.54 (d, J = 7.6 Hz, 1H), 4.01–3.96 (m, 2H), 3.85 (t, J
= 9.1 Hz, 1H), 3.72 (t, J = 8.8 Hz, 1H), 3.59–3.52 (m, 2H),
1.70–1.64(m, 2H), 1.43–1.30 (m, 8H), 0.92–0.89 (m, 3H).13C
NMR (125 MHz, CDCl3) δ 172.9, 138.2, 138.1, 137.4, 128.4,
128.4, 128.1, 128.1, 127.9, 127.8, 127.7, 127.7, 103.7, 83.5,
-
20
81.5, 78.8, 75.6, 75.0, 74.7, 74.0, 70.5, 31.6, 29.6, 25.7, 22.5,
14.0.HRMS: Calc. for C33H41O7[M+H]+:549.2852, Obser.
549.2849
(Phenylmethyl)-2,3,4-tri-O-benzyl-D-glucopyranosiduronic acid (5b)
Viscous liquid. (130 mg, 94%); Rf value =0.6 in 50% EtOAc/ Hexane.
IR:νmax (neat) 3215, 1705, 1145 cm-1. β:α isomer (>20:1);[α]D
24= -19.6 [c
0.1, CHCl3];1H NMR (500 MHz, CDCl3) δ 7.37-7.24 (m, 21H), 4.98 (d, J
= 12.1 Hz, 1H), 4.90 (dd, J = 15.9, 10.9 Hz, 2H), 4.79 (t, J = 10.4 Hz,
2H), 4.68 (ddd, J = 18.2, 16.6, 9.2 Hz, 4H), 4.00 (d, J = 9.3 Hz, 1H),
3.88–3.84 (m, 1H), 3.70 (t, J = 8.7 Hz, 1H), 3.59 (t, J = 7.7 Hz, 1H). 13C
NMR (125 MHz, CDCl3) δ 172.7, 138.2, 138.0, 137.4, 136.9, 128.5,
128.4, 128.4, 128.3, 128.1, 128.0, 128.0, 127.9, 127.8, 127.7, 127.7,
102.5, 83.5, 81.6, 78.7, 75.6, 75.0, 74.8, 74.0, 71.5. HRMS: Calc. for
C34H35O7[M+H]+:555.2383, Obser. 555.2387
(2S,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-(((2R,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-methoxytetra-
hydro-2H-pyran-2-yl)methoxy)tetrahydro-2H-pyran-2-carboxylic acid (5c)
White solid (198 mg, 87%); M.P: 93-95 oC; Rfvalue =0.5 in 60%
EtOAc/ Hexane. IR:νmax (neat) 3345, 1701, 1065 cm-1. β:α isomer
(3:2); [α]D24= +34.5 [c 0.1, CHCl3];
1H NMR (500 MHz, CDCl3) δ
7.38–7.19 (m, 31H), 5.01–4.50 (m, 14H), 4.10–3.44 (m, 10H),
3.36 (d, J = 20.3 Hz, 3H).13C NMR (125 MHz, CDCl3) δ172.0,
170.4, 138.8, 138.7, 138.3, 138.2, 138.2, 138.1, 138.1, 138.0,
138.0, 137.5, 137.5, 128.4, 128.4, 128.3, 128.3, 128.3, 128.1,
128.1, 128.0, 128.0, 127.9, 127.9, 127.8, 127.8, 127.8, 127.7,
127.7, 127.6, 127.5, 103.5, 98.1, 98.0, 97.5, 96.1, 83.1, 82.0, 81.9,
81.2, 80.9, 80.1, 79.9, 79.3, 79.0, 78.7, 77.8, 77.7, 75.7, 75.7,
75.6, 75.3, 75.1, 75.0, 74.9, 74.8, 74.6, 73.9, 73.3, 72.6, 70.3,
69.9, 69.4, 69.0, 66.7, 55.3, 55.2.HRMS: Calc. for
C55H59O12[M+H]+:911.4007, Obser. 911.4012
-
21
References:
1. D. J. Chambers, G. R. Evans and A. J. Fairbanks, Tetrahedron 2005, 61, 7184–7192.
(Phenylmethyl)-2, 3, 4-tri-O-benzyl-D-glucopyranosiduronic acid (5d)
Viscous liquid. (116 mg, 84%); Rf value = 0.6 in 50% EtOAc/ Hexane.
IR:νmax (neat) 3217, 1708, 1085 cm-1.β:α isomer (~3:1);[α]D
24= +8.8 [c
0.1, CHCl3];1H NMR (500 MHz, CDCl3) δ 7.43–7.26 (m, 20H), 5.00 (dd,
J = 17.1, 11.4 Hz, 1H), 4.93–4.85 (m, 2H), 4.83–4.66 (m, 5H), 4.03 (d, J
= 9.1 Hz, 1H), 3.87 (t, J = 8.9 Hz, 1H), 3.71 (t, J = 8.6 Hz, 1H), 3.61–
3.58 (m, 1H).13C NMR (125 MHz, CDCl3) δ 174.0, 173.0, 138.5, 138.2,
138.0, 137.8, 137.5, 136.96, 136.5, 128.5, 128.5, 128.5, 128.4, 128.4,
128.4, 128.2, 128.1, 128.1, 128.0, 128.0, 128.0, 127.9, 127.9, 127.8,
127.7, 127.7, 102.6, 95.9, 83.6, 81.6, 81.4, 79.3, 79.1, 78.7, 75.9, 75.6,
75.3, 75.0, 74.8, 74.0, 73.2, 71.5, 69.9, 69.7. HRMS: Calc. for C34H35O7
[M+H]+:555.2383, Obser. 555.2381
-
22
1H-NMR (500 MHz, CDCl3) spectrum of compound AB
13
C-NMR (125 MHz, CDCl3) spectrum of compound AB
1.1
7
3.0
8
2.0
7
2.0
6
1.0
2
1.0
1
2.0
4
1.0
3
3.0
8
1.0
0
2.0
4
10.0
0
2.0
1
1.9
53
3.3
51
3.4
74
3.4
81
3.4
93
3.5
00
3.5
06
3.5
25
3.6
59
3.6
83
3.6
91
3.7
48
3.7
53
3.9
61
3.9
80
4.5
60
4.5
68
4.5
75
4.5
83
4.6
57
4.7
55
4.7
58
4.7
77
4.7
80
4.9
66
4.9
88
7.0
99
7.1
16
7.2
22
7.2
59
7.2
62
7.2
66
7.2
73
7.2
83
7.2
86
7.2
90
7.2
97
7.3
03
7.3
11
7.3
20
7.3
25
7.3
28
7.3
41
7.3
55
7.3
58
7.3
93
7.3
97
7.4
11
7.4
14
55.3
51
61.8
48
70.7
99
73.4
85
74.2
48
75.8
03
77.0
06
77.2
60
77.5
15
77.6
61
81.9
36
98.2
68
121.7
31
127.7
63
127.9
81
128.0
89
128.2
19
128.5
34
128.6
09
129.5
57
131.6
22
137.3
89
138.1
93
138.8
16
-
23
1H-NMR (500 MHz, CDCl3) spectrum of compound AC
13
C-NMR (125 MHz, CDCl3) spectrum of compound AC
1.1
2
3.0
4
1.0
6
1.0
5
2.0
3
1.0
1
1.0
0
1.0
2
1.0
4
2.0
3
1.0
3
2.0
2
10.0
8
1.0
6
2.0
6
1.0
0
3.0
3
1.8
91
3.3
49
3.4
98
3.5
05
3.5
17
3.5
24
3.5
78
3.5
97
3.6
73
3.6
78
3.6
96
3.7
18
3.7
26
3.7
69
3.7
74
3.7
92
4.0
21
4.0
39
4.0
58
4.5
69
4.5
76
4.6
40
4.6
64
4.7
68
4.7
83
4.7
93
4.8
06
4.8
41
4.8
63
4.9
93
5.0
06
5.0
15
5.0
29
7.1
92
7.2
63
7.2
70
7.2
77
7.2
81
7.2
86
7.2
96
7.3
01
7.3
07
7.3
10
7.3
18
7.3
24
7.3
27
7.3
45
7.3
57
7.3
61
7.3
76
7.3
79
7.3
93
7.3
96
7.4
23
7.4
25
7.4
34
7.4
41
7.4
44
7.6
93
7.7
49
7.7
63
7.7
74
7.7
80
7.7
92
55.3
40
61.9
99
70.9
06
73.5
38
75.8
76
77.0
05
77.2
60
77.5
14
77.6
83
80.1
86
82.1
02
98.3
24
126.0
31
126.0
85
126.2
59
126.8
21
127.7
57
127.8
36
128.0
95
128.2
52
128.3
64
128.5
53
128.6
22
133.1
35
133.4
14
135.7
85
138.2
81
138.9
30
-
24
1H-NMR (500 MHz, CDCl3) spectrum of compound 1a
13C-NMR (125 MHz, CDCl3) spectrum of compound 1a
3.0
0
1.0
4
1.0
2
1.0
0
1.0
0
1.0
6
2.0
8
3.0
3
1.0
2
1.9
1
1.9
4
2.1
4
11.0
2
2.0
8
1.0
7
1.0
4
3.4
73
3.6
32
3.6
39
3.6
51
3.6
58
3.8
18
3.8
37
3.8
56
4.0
56
4.0
75
4.0
93
4.3
27
4.3
47
4.5
87
4.6
09
4.6
81
4.6
87
4.7
12
4.8
41
4.8
54
4.8
65
4.8
77
4.8
99
5.0
07
5.0
28
5.5
25
5.5
55
5.5
70
5.6
00
7.1
95
7.2
03
7.2
10
7.2
62
7.2
67
7.2
73
7.2
75
7.2
83
7.3
22
7.3
29
7.3
35
7.3
38
7.3
44
7.3
49
7.3
53
7.3
59
7.3
72
7.3
86
7.3
88
7.3
94
7.4
09
7.4
30
7.4
38
7.4
45
7.4
50
7.4
57
7.4
65
7.5
17
7.5
24
7.5
29
7.5
36
8.1
10
8.1
17
8.1
22
8.1
29
55.7
64
63.7
25
70.3
23
73.6
73
75.0
64
75.9
53
76.8
76
77.1
31
77.3
85
79.3
11
79.4
15
81.5
02
98.8
47
125.0
72
127.7
45
127.7
71
128.0
30
128.1
16
128.2
13
128.3
67
128.4
76
128.5
82
128.6
21
128.7
28
131.5
90
133.9
05
137.9
25
138.4
65
147.1
91
169.1
09
OBnOBnO
BnOOCH3
O
O
NO2
1a
OBnOBnO
BnOOCH3
O
O
NO2
1a
-
25
1H-NMR (500 MHz, CDCl3) spectrum of compound 1b
13C-NMR (125 MHz, CDCl3) spectrum of compound 1b
-
26
1H-NMR (500 MHz, CDCl3) spectrum of compound 1c
13C-NMR (125 MHz, CDCl3) spectrum of compound 1c
3.0
2
3.0
0
3.0
1
1.0
1
1.0
0
2.0
1
1.0
0
1.0
1
3.0
0
1.7
0
4.4
4
3.0
3
0.9
7
1.9
88
2.0
96
3.4
80
3.9
45
3.9
64
3.9
84
4.3
91
4.4
10
4.5
91
4.9
11
4.9
97
5.0
05
5.5
65
5.5
80
5.5
96
5.6
23
5.6
53
7.1
85
7.1
96
7.2
00
7.2
72
7.2
76
7.2
84
7.2
90
7.5
00
7.5
16
7.5
18
7.5
47
8.1
35
8.1
38
8.1
53
-
27
1H-NMR (500 MHz, CDCl3) spectrum of compound 1d
13C-NMR (125 MHz, CDCl3) spectrum of compound 1d
3.0
0
1.0
2
1.0
0
2.0
3
2.0
2
2.0
2
1.0
0
5.0
0
4.0
4
5.0
1
4.0
1
1.0
0
3.5
07
4.1
98
4.2
17
4.2
36
4.5
39
4.5
59
4.6
07
4.6
10
5.2
14
5.2
22
5.2
35
5.2
42
5.2
58
5.2
65
5.5
98
5.6
29
5.6
62
5.6
93
6.0
88
6.1
07
6.1
27
7.0
84
7.0
92
7.0
99
7.1
03
7.1
46
7.1
50
7.1
56
7.1
60
7.2
81
7.2
81
7.3
77
7.3
88
7.3
93
7.4
03
7.4
04
7.4
08
7.4
18
7.4
95
7.5
11
7.5
14
7.5
16
7.5
19
7.5
29
7.5
31
7.5
33
7.5
39
7.5
41
7.5
48
7.5
88
7.6
03
7.9
84
7.9
86
7.9
91
7.9
94
7.9
98
8.0
01
8.0
02
8.0
08
8.0
10
8.1
52
8.1
54
8.1
68
8.1
70
55.8
38
63.8
77
70.0
89
71.7
03
71.8
63
74.7
13
77.4
46
97.5
05
125.0
77
127.8
27
127.9
52
128.2
28
128.3
87
128.4
23
128.7
51
128.8
72
129.6
44
129.8
89
131.4
60
133.2
24
133.3
65
133.9
73
136.9
98
147.0
93
165.4
71
165.8
92
168.4
68
-
28
1H-NMR (500 MHz, CDCl3) spectrum of compound 1e
13C-NMR (125 MHz, CDCl3) spectrum of compound 1e
55.6
64
63.5
31
72.0
23
72.3
96
72.9
55
74.3
02
74.5
39
75.6
63
78.7
18
99.7
51
125.0
20
127.6
84
127.6
99
127.7
23
127.8
46
128.3
51
128.3
98
128.5
51
128.5
85
131.9
22
133.8
82
138.0
42
138.0
73
138.2
67
147.1
37
168.8
97
-
29
1H-NMR (500 MHz, CDCl3) spectrum of compound 1f
13C-NMR (125 MHz, CDCl3) spectrum of compound 1f
3.0
0
1.0
0
0.9
8
0.9
9
1.0
0
0.9
8
0.9
8
0.9
6
2.4
1
7.0
3
1.0
3
2.0
6
1.9
5
1.9
2
3.9
3
3.5
75
4.4
67
4.5
21
4.5
30
4.5
45
4.5
54
4.7
33
4.7
37
4.7
57
4.7
62
5.0
39
5.7
33
5.7
36
5.7
39
5.7
43
5.9
55
5.9
62
6.1
28
6.1
48
7.2
82
7.2
83
7.2
87
7.3
03
7.3
86
7.4
01
7.4
25
7.4
40
7.4
47
7.4
55
7.6
01
7.8
63
7.8
79
7.9
79
7.9
94
7.9
95
8.0
83
8.1
00
8.1
25
8.1
39
8.1
41
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
55.6
03
62.9
49
66.9
74
68.7
81
70.0
69
70.4
46
98.7
22
128.3
06
128.4
68
128.6
05
129.0
18
129.1
22
129.3
58
129.7
50
129.7
57
129.8
19
129.8
69
129.8
94
133.0
85
133.1
78
133.4
51
133.4
83
165.4
46
165.5
02
166.2
04
OBzOBzO
OBz
OCH3
O
O
NO2
1f
-
30
1H-NMR (500 MHz, CDCl3) spectrum of compound 1g
13C-NMR (125 MHz, CDCl3) spectrum of compound 1g
OBzOBzO
OBz
O
ONO2
SPh
1g
OBzOBzO
OBz
O
ONO2
SPh
1g
-
1H-NMR (500 MHz, CDCl
13C-NMR (125 MHz, CDCl
500 MHz, CDCl3) spectrum of compound 1h
125 MHz, CDCl3) spectrum of compound 1h
31
-
32
1H-NMR (500 MHz, CDCl3) spectrum of compound 1i
13C-NMR (125 MHz, CDCl3) spectrum of compound 1i
-
33
1H-NMR (500 MHz, CDCl3) spectrum of compound 1j
13C-NMR (125 MHz, CDCl3) spectrum of compound 1j
-
34
1H-NMR (500 MHz, CDCl3) spectrum of compound 1k
13C-NMR (125 MHz, CDCl3) spectrum of compound 1k
OHOBzO
BzOOCH3
O
ONO2
1k
OHOBzO
BzOOCH3
O
ONO2
1k
-
35
1H-NMR (500 MHz, CDCl3) spectrum of compound 1l
13C-NMR (125 MHz, CDCl3) spectrum of compound 1l
-
36
1H-NMR (500 MHz, CDCl3) spectrum of compound 1m
13C-NMR (125 MHz, CDCl3) spectrum of compound 1m
3.0
0
1.0
0
1.0
0
1.0
0
1.0
0
1.0
0
2.0
1
3.0
0
1.0
0
2.0
1
2.0
0
12.0
3
3.0
4
1.0
0
3.4
56
3.5
97
3.6
04
3.6
16
3.6
23
3.7
54
3.7
74
3.7
92
4.0
04
4.0
23
4.0
41
4.2
78
4.2
98
4.4
92
4.5
14
4.6
58
4.6
64
4.6
86
4.7
64
4.7
72
4.7
87
4.7
94
4.8
12
4.8
37
4.9
84
5.0
06
5.5
36
5.5
66
5.5
82
5.6
12
7.0
12
7.0
28
7.2
81
7.3
26
7.3
35
7.3
38
7.3
44
7.3
60
7.3
72
7.4
70
7.4
80
7.4
84
8.1
07
8.1
18
8.1
25
55.7
66
63.7
84
70.1
89
73.6
23
74.1
54
75.8
67
79.3
31
79.4
45
81.3
39
98.8
05
125.1
22
127.7
60
127.8
98
128.1
07
128.1
74
128.4
54
128.5
63
128.7
49
128.8
84
129.2
19
131.3
36
131.3
80
133.7
70
136.9
73
137.8
56
138.4
07
147.3
20
169.0
59
OOBnO
BnOOCH3
O
O
NO2
1m
Br
OOBnO
BnOOCH3
O
O
NO2
1m
Br
-
37
1H-NMR (500 MHz, CDCl3) spectrum of compound 1n
13C-NMR (125 MHz, CDCl3) spectrum of compound 1n
3.0
0
1.0
1
1.0
1
1.0
0
1.0
1
3.0
1
2.0
2
2.0
0
2.0
2
17.3
9
1.0
1
2.0
0
1.0
2
0.9
5
3.4
72
3.6
44
3.6
51
3.6
64
3.6
70
3.8
59
3.8
78
3.8
97
4.0
80
4.0
99
4.1
17
4.3
45
4.3
65
4.6
90
4.7
15
4.8
42
5.0
23
5.4
40
5.4
70
5.5
31
5.5
61
7.2
69
7.2
82
7.2
95
7.3
08
7.3
25
7.3
35
7.3
41
7.3
47
7.3
56
7.3
70
7.3
84
7.3
86
7.3
94
7.4
06
7.4
20
7.4
46
7.4
53
7.4
61
7.6
14
7.6
86
7.7
04
7.7
14
7.7
31
7.7
80
8.0
22
8.0
37
55.7
71
63.7
39
70.3
77
73.6
66
75.1
23
75.9
38
79.3
91
79.4
65
81.5
14
98.8
60
124.9
59
125.7
22
125.9
09
126.0
69
126.4
59
127.6
29
127.7
47
127.8
33
128.0
11
128.0
58
128.0
99
128.1
94
128.4
62
128.5
68
133.7
19
147.0
27
169.0
92
-
38
1H-NMR (500 MHz, CDCl3) spectrum of compound 1o
13C-NMR (125 MHz, CDCl3) spectrum of compound 1o
OO
O
O
BnOBnO
BnO
O
BnOBnO
SPh
NO2O
O
NO2
1o
OO
O
O
BnOBnO
BnO
O
BnOBnO
SPh
NO2O
O
NO2
1o
-
39
1H-NMR (500 MHz, CDCl3) spectrum of compound 4a
13C-NMR (125 MHz, CDCl3) spectrum of compound 4a
3.0
1
7.0
6
2.9
7
2.0
0
1.0
1
1.0
0
2.0
3
0.9
9
1.0
0
0.9
8
2.0
7
2.0
8
1.0
2
1.0
1
2.0
2
2.9
5
10.1
5
2.0
5
1.0
2
1.0
0
0.8
99
0.9
13
0.9
23
0.9
27
1.3
20
1.3
27
1.3
35
1.3
42
1.6
87
1.6
99
3.5
52
3.5
54
3.5
70
3.7
16
3.7
34
3.9
20
3.9
38
4.0
27
4.0
46
4.5
20
4.5
35
4.6
04
4.6
26
4.7
51
4.7
73
4.8
19
4.8
41
4.8
53
4.8
75
4.9
54
4.9
73
4.9
75
4.9
94
5.5
14
5.5
44
5.6
19
5.6
49
7.1
85
7.1
89
7.1
97
7.2
04
7.2
66
7.2
70
7.2
77
7.2
82
7.3
16
7.3
20
7.3
27
7.3
29
7.3
33
7.3
37
7.3
43
7.3
49
7.3
52
7.3
65
7.3
70
7.3
74
7.4
62
7.4
64
7.4
70
7.4
78
7.4
83
8.1
32
8.1
51
14.0
52
22.5
97
25.8
26
29.6
97
31.6
24
63.6
06
70.5
30
74.5
97
74.8
90
74.9
65
75.7
73
78.9
78
81.7
86
83.9
64
104.0
49
125.0
59
127.7
23
127.7
79
127.8
02
127.8
59
127.9
07
128.1
56
128.3
59
128.4
11
128.5
43
128.6
61
131.7
58
133.8
54
138.3
20
147.1
60
167.9
92
-
40
1H-NMR (500 MHz, CDCl3) spectrum of compound 4b
13C-NMR (125 MHz, CDCl3) spectrum of compound 4b
1.0
2
1.0
1
1.0
2
1.0
0
2.1
4
2.1
5
2.2
1
3.1
2
2.1
8
2.0
9
19.3
5
2.2
3
1.0
0
1.0
4
3.6
28
3.6
43
3.7
20
3.7
38
3.9
51
3.9
69
4.0
44
4.0
64
4.6
13
4.6
35
4.6
43
4.6
58
4.6
97
4.7
21
4.7
43
4.7
64
4.8
11
4.8
32
4.8
54
4.8
76
4.9
38
4.9
58
4.9
79
4.9
97
5.0
21
5.5
27
5.5
58
5.6
27
7.1
87
7.1
92
7.2
00
7.2
07
7.2
68
7.2
72
7.2
78
7.2
82
7.3
04
7.3
10
7.3
12
7.3
19
7.3
22
7.3
28
7.3
31
7.3
37
7.3
39
7.3
48
7.3
52
7.3
56
7.3
60
7.3
68
7.3
71
7.3
84
7.3
99
7.4
01
7.4
03
7.4
14
7.4
61
7.4
66
7.4
69
7.4
72
7.4
75
7.4
80
8.1
35
8.1
54
63.7
07
71.4
50
74.6
26
74.9
53
75.7
72
78.9
36
81.8
13
83.9
44
102.8
45
127.7
52
127.7
91
127.8
19
127.8
52
127.9
13
127.9
87
128.0
35
128.1
92
128.3
73
128.4
05
128.4
30
128.5
11
128.7
45
133.8
81
147.2
32
167.9
93
-
41
1H-NMR (500 MHz, CDCl3) spectrum of compound 4c
13C-NMR (125 MHz, CDCl3) spectrum of compound 4c
O
O
O
O
O
BnOBnO
BnO BnO
BnOBnO
O
NO2
4c
O
O
O
O
O
BnOBnO
BnO BnO
BnOBnO
O
NO2
4c
-
42
1H-NMR (500 MHz, CDCl3) spectrum of compound 4d
13
C-NMR (125 MHz, CDCl3) spectrum of compound 4d
1.0
0
0.7
6
0.7
8
0.7
5
2.0
9
4.0
1
2.9
5
2.0
0
24.0
2
0.9
4
3.6
25
3.6
43
3.6
58
3.7
34
3.7
52
3.7
70
3.9
48
3.9
67
3.9
85
4.0
59
4.0
79
4.6
51
4.6
57
4.7
11
4.7
34
4.9
72
5.5
38
5.5
69
5.5
85
5.6
38
5.6
69
7.2
15
7.2
82
7.2
90
7.3
33
7.3
60
7.3
63
7.3
68
7.3
83
7.4
13
7.4
68
7.4
77
8.1
41
8.1
46
8.1
49
8.1
55
8.1
59
63.7
17
69.6
33
71.4
57
74.6
45
74.9
63
75.7
81
75.8
99
78.9
53
79.4
01
81.8
30
83.9
62
96.1
13
102.8
60
127.7
64
127.8
00
127.8
28
127.8
62
127.9
25
127.9
97
128.0
48
128.2
02
128.3
86
128.4
17
128.4
43
128.5
25
128.7
58
133.8
87
147.2
47
168.0
02
169.1
15
-
43
1H-NMR (500 MHz, CDCl3) spectrum of compound 1aa
13C-NMR (125 MHz, CDCl3) spectrum of compound 1aa
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.0
2
1.0
0
2.0
0
2.0
1
2.0
6
1.0
0
2.0
5
1.0
0
2.0
6
3.0
2
10.0
7
3.0
7
1.0
0
0.9
3
3.8
72
3.8
79
3.8
91
3.8
98
3.9
35
3.9
53
3.9
73
4.1
46
4.1
64
4.1
83
4.5
72
4.5
93
4.6
31
4.6
52
4.7
48
4.7
71
4.7
98
4.8
22
4.8
89
4.9
11
4.9
34
5.0
14
5.0
36
5.5
17
5.5
47
5.5
76
5.6
07
6.6
08
6.6
15
7.2
21
7.2
26
7.2
33
7.2
40
7.2
82
7.2
90
7.2
95
7.2
99
7.3
03
7.3
33
7.3
36
7.3
45
7.3
51
7.3
53
7.3
60
7.3
61
7.3
68
7.3
70
7.3
75
7.4
61
7.4
65
7.4
76
7.4
80
7.4
91
7.4
94
7.5
05
7.5
29
7.5
31
7.5
43
7.5
47
8.1
24
8.1
28
8.1
40
8.1
43
8.7
49
0102030405060708090100110120130140150160170180f1 (ppm)
-
44
1H-NMR (500 MHz, DMSO-d6) spectrum of compound 2a
13C-NMR (125 MHz, DMSO-d6) spectrum of compound 2a
3.0
0
1.0
0
1.0
0
1.0
0
1.0
0
1.0
0
4.0
0
0.8
9
0.9
5
16.0
0
2.4
97
2.5
00
2.5
04
2.5
08
2.5
11
3.3
02
3.3
45
3.5
70
3.6
43
3.7
94
3.9
24
3.9
44
4.5
89
4.6
69
4.6
75
4.7
17
4.7
37
4.7
40
4.8
33
4.8
56
4.9
11
4.9
18
7.2
29
7.2
42
7.2
45
7.2
58
7.2
65
7.2
72
7.2
77
7.2
81
7.2
83
7.2
86
7.2
89
7.2
97
7.3
01
7.3
04
7.3
06
7.3
12
7.3
16
7.3
22
7.3
24
7.3
29
7.3
33
7.3
41
7.3
45
7.3
58
7.3
69
7.3
74
7.3
77
7.4
00
55.3
72
70.4
92
72.0
63
74.5
30
75.0
01
79.6
50
80.8
51
98.0
20
127.8
69
127.8
93
127.9
45
127.9
70
128.0
14
128.1
17
128.1
45
128.6
20
128.6
30
128.7
06
138.6
07
138.8
32
139.0
71
170.9
59
-
45
1H-NMR (500 MHz, CDCl3) spectrum of compound 2b
13C-NMR (125 MHz, CDCl3) spectrum of compound 2b
3.0
0
1.0
0
1.0
0
1.0
0
1.0
0
1.0
0
2.0
0
4.0
0
1.0
1
2.0
0
6.0
0
3.5
43
4.6
52
4.6
73
5.3
25
5.3
45
5.3
70
5.3
77
5.7
55
5.7
74
6.1
81
6.2
01
6.2
21
7.3
23
7.3
79
7.3
95
7.4
02
7.4
17
7.5
24
7.5
39
7.8
95
7.8
97
7.9
12
7.9
13
7.9
47
7.9
50
7.9
64
7.9
65
7.9
87
7.9
89
8.0
04
8.0
05
56.3
43
68.0
80
69.8
17
71.4
79
77.2
34
97.4
32
128.3
45
128.4
06
128.4
66
128.8
73
129.0
32
129.7
42
129.9
05
129.9
64
133.2
47
133.4
01
133.4
90
165.4
10
165.6
85
165.7
63
171.1
12
OBzOBzO
BzOOCH3
OH
O
2b
OBzOBzO
BzOOCH3
OH
O
2b
-
46
1H-NMR (500 MHz, CDCl3) spectrum of compound 2c
13C-NMR (125 MHz, CDCl3) spectrum of compound 2c
3.0
0
3.0
3
3.0
3
1.0
8
1.0
6
3.0
2
1.0
9
1.0
3
1.0
6
2.0
5
3.4
2
1.9
71
2.0
85
3.4
61
3.8
74
3.8
94
3.9
13
4.3
25
4.3
45
4.6
02
4.6
89
4.7
12
4.9
89
4.9
96
5.5
55
5.5
74
5.5
94
7.2
51
7.2
64
7.2
67
7.2
82
7.2
94
7.2
97
7.3
00
7.3
12
7.3
23
7.3
26
7.3
40
7.3
43
7.3
46
20.7
14
20.7
81
55.8
10
69.4
39
70.8
58
71.3
00
74.7
57
77.5
39
97.3
06
128.0
10
128.0
46
128.4
80
137.2
15
169.7
64
170.3
85
172.2
30
-
47
1H-NMR (500 MHz, CDCl3) spectrum of compound 2d
13C-NMR (125 MHz, CDCl3) spectrum of compound 2d
3.0
0
1.0
1
1.0
0
2.0
0
2.0
1
1.0
0
5.1
5
4.0
2
2.0
1
4.0
3
3.5
83
4.2
80
4.2
99
4.6
04
4.6
23
4.7
18
4.7
40
4.7
94
4.8
16
5.3
29
5.3
36
5.3
56
5.3
67
5.3
75
6.1
87
6.2
06
6.2
26
7.2
60
7.4
61
7.4
76
7.4
93
7.4
96
7.5
12
7.6
09
7.6
25
8.0
86
8.0
88
8.0
91
8.0
94
8.1
03
8.1
05
8.1
08
55.9
82
69.8
00
71.7
77
71.9
35
74.8
30
76.9
01
77.1
55
77.3
58
77.4
09
97.5
08
128.0
37
128.2
38
128.3
73
128.4
99
128.8
99
129.4
24
129.7
64
129.9
97
133.3
61
133.5
23
136.9
02
165.6
54
166.0
85
173.6
84
-
48
1H-NMR (500 MHz, CDCl3) spectrum of compound 2e
13C-NMR (125 MHz, CDCl3) spectrum of compound 2e
3.0
0
1.0
0
1.0
0
2.0
0
2.0
0
4.0
2
1.0
0
15.1
1
3.4
62
3.4
64
3.7
95
3.7
97
3.8
01
4.2
33
4.3
06
4.6
32
4.6
39
4.7
02
4.7
25
4.7
51
4.7
77
4.8
02
4.8
24
4.9
65
7.2
81
7.3
02
7.3
16
7.3
27
7.3
43
7.3
48
7.3
50
7.3
64
7.3
67
7.3
81
7.3
84
7.3
91
55.7
67
71.3
70
72.4
30
72.9
91
74.5
23
75.6
56
78.5
35
99.6
26
127.6
92
127.7
09
127.7
42
127.8
72
127.9
21
128.1
09
128.4
23
137.7
63
138.0
76
138.1
93
174.1
30
-
49
1H-NMR (500 MHz, CDCl3) spectrum of compound 2f
13C-NMR (125 MHz, CDCl3) spectrum of compound 2f
3.0
0
1.0
0
1.0
1
1.0
1
1.0
3
1.0
8
2.0
7
2.0
1
4.0
3
1.0
4
2.0
0
2.0
1
2.0
1
3.5
95
4.6
83
4.7
02
5.1
54
5.1
58
5.6
85
5.6
90
5.6
91
5.6
96
5.9
27
5.9
34
6.0
28
6.0
47
7.2
82
7.2
93
7.3
08
7.3
24
7.3
86
7.4
02
7.4
67
7.4
78
7.4
93
7.5
09
7.8
60
7.8
62
7.8
77
7.8
79
7.9
70
7.9
72
7.9
86
8.0
93
8.0
95
8.1
10
8.1
12
56.2
43
67.4
42
69.3
59
69.4
16
69.8
91
98.8
93
128.3
64
128.4
21
128.6
24
128.9
41
129.0
17
129.1
10
129.7
85
129.8
56
129.9
82
133.3
12
133.4
07
133.6
14
165.3
03
165.4
99
165.5
42
171.4
62
-
50
1H-NMR (500 MHz, CDCl3) spectrum of compound 2g
13
C-NMR (125 MHz, CDCl3) spectrum of compound 2g
1.0
0
1.0
0
1.0
2
1.0
1
1.0
2
14.1
2
2.0
0
2.0
1
2.0
0
4.3
85
4.4
04
5.0
96
5.1
15
5.5
20
5.5
39
5.5
59
5.7
15
5.7
34
5.7
53
5.8
99
5.9
17
7.2
82
7.2
98
7.3
14
7.3
23
7.3
27
7.3
34
7.3
37
7.3
51
7.4
10
7.5
43
7.5
50
7.5
58
7.8
32
7.8
34
7.8
49
7.9
12
7.9
15
7.9
29
7.9
76
7.9
78
7.9
92
66.2
31
69.9
94
70.3
35
73.8
46
86.5
66
128.2
93
128.3
50
128.4
14
128.4
97
128.8
08
129.0
62
129.0
83
129.2
02
129.8
26
129.8
77
129.8
98
131.7
37
133.2
47
133.3
12
133.3
38
164.9
87
165.1
17
165.6
74
170.4
20
-
51
1H-NMR (500 MHz, CDCl3) spectrum of compound 2h
13C-NMR (125 MHz, CDCl3) spectrum of compound 2h
1.0
0
1.0
2
1.0
1
1.0
0
1.0
0
3.0
4
2.0
7
1.0
0
19.4
4
2.0
5
3.5
61
3.5
78
3.5
81
3.5
97
3.7
54
3.7
71
3.7
88
3.8
56
3.8
74
3.8
92
4.0
05
4.0
23
4.7
09
4.7
59
4.7
74
4.7
80
4.7
94
4.8
13
4.8
66
4.8
76
4.9
21
4.9
42
7.2
74
7.2
80
7.2
82
7.2
86
7.2
96
7.3
12
7.3
14
7.3
17
7.3
28
7.3
35
7.3
42
7.3
45
7.3
46
7.3
50
7.3
54
7.3
58
7.3
61
7.3
73
7.3
77
7.4
08
7.4
10
7.5
85
7.5
88
7.6
00
7.6
04
75.0
64
75.4
45
75.7
56
77.5
21
78.7
49
80.2
89
85.3
70
88.1
33
127.8
56
127.9
99
128.0
52
128.1
78
128.2
42
128.4
62
128.4
84
128.5
14
129.1
36
132.3
66
133.0
68
137.3
77
137.7
95
138.0
28
172.3
92
OBnOBnO
OBn
OH
O
SPh
2h
OBnOBnO
OBn
OH
O
SPh
2h
-
52
1H-NMR (500 MHz, DMSO-d6) spectrum of compound 2i
13C-NMR (125 MHz, DMSO-d6) spectrum of compound 2i
6.0
1
3.0
0
3.0
0
1.0
1
1.0
1
1.0
3
1.0
4
1.0
0
1.2
74
1.2
81
1.3
20
1.4
31
2.4
93
2.4
96
2.5
00
2.5
04
3.3
66
4.1
79
4.1
84
4.3
91
4.3
96
4.4
01
4.4
06
4.4
96
4.5
12
4.5
16
4.6
37
4.6
42
5.5
27
5.5
37
24.8
73
25.1
19
26.1
34
26.2
80
67.7
03
69.9
93
70.5
16
71.9
25
96.2
30
108.5
41
109.1
76
169.3
44
-
53
1H-NMR (500 MHz, CDCl3) spectrum of compound 2j
13C-NMR (125 MHz, CDCl3) spectrum of compound 2j
-
54
1H-NMR (500 MHz, Methanol-d4) spectrum of compound 2k
13C-NMR (125 MHz, Methanol-d4) spectrum of compound 2k
3.0
0
1.0
3
1.0
0
2.0
0
1.0
0
4.0
0
2.0
1
2.0
2
2.0
0
3.4
97
4.0
73
4.0
93
4.1
12
4.2
67
4.2
87
5.1
83
5.1
91
5.2
03
5.2
06
5.7
88
5.7
92
5.8
07
5.8
11
5.8
14
5.8
30
7.3
87
7.3
90
7.4
03
7.4
06
7.4
22
7.5
37
7.9
03
7.9
07
7.9
10
7.9
24
7.9
83
7.9
86
8.0
00
54.7
78
69.8
65
71.1
76
71.7
25
72.5
28
97.5
54
128.1
06
128.1
46
128.9
33
129.2
29
129.3
03
129.6
16
132.9
68
133.2
26
165.6
75
166.1
72
170.9
20
-
55
1H-NMR (500 MHz, CDCl3) spectrum of compound 2l
13C-NMR (125 MHz, CDCl3) spectrum of compound 2l
2.0
2
0.9
6
1.0
1
2.0
5
1.0
0
1.0
0
1.0
0
3.1
7
8.0
4
4.0
46
4.0
57
4.0
69
4.0
99
4.1
70
4.1
77
4.3
18
4.3
43
4.3
79
4.4
03
4.6
34
4.6
64
4.7
38
6.1
38
6.1
48
7.1
59
7.1
74
7.1
89
7.2
79
7.2
93
7.3
07
7.3
27
7.3
63
7.3
72
47.5
15
64.2
07
72.6
59
76.9
28
77.1
82
77.4
37
79.5
35
101.2
51
127.8
63
128.2
67
128.3
54
128.6
40
128.6
66
129.2
18
134.7
26
136.3
23
156.8
54
169.3
48
-
56
1H-NMR (500 MHz, CDCl3) spectrum of compound 2m