ACD/Labs NMR Software Symposium · 2016-09-29 · 9/28/2016 Advanced Chemistry Development, Inc....
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ACD/Labs NMR Software Symposium Seven Novel Structures Generated with Computer- Assisted Structure Elucidation Arvin Moser SMASH September 11, 2016
Transcript of ACD/Labs NMR Software Symposium · 2016-09-29 · 9/28/2016 Advanced Chemistry Development, Inc....
ACD/Labs NMR Software Symposium
Seven Novel Structures Generated with Computer-Assisted Structure Elucidation
Arvin Moser
SMASH
September 11, 2016
Relevant Quote
Galileo Galilei 1564-1642
" All truths are easy to understand once they are discovered; the point is to discover them ".*
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*Angels in the workplace : stories and inspirations for creating a new world of work (1999) by Melissa Giovagnoli
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Naman, CB, Li, J, Moser, A, Hendrycks, JM, Benatrehina, PA, Chai, H, Yuan, C, Keller, WJ, Kinghorn, AD. Computer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton. Organic Letters, 2015, 17, 2988-2991.
MF, 1H, 13C, HSQC, HMBC, COSY in solvent CD3OD, 176400 molecule(s) have been generated by Correlation Spectroscopy Based Generator and 42 molecule(s) have been stored. Generation time: 23 seconds
TOP Structure
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Naman, CB, Li, J, Moser, A, Hendrycks, JM, Benatrehina, PA, Chai, H, Yuan, C, Keller, WJ, Kinghorn, AD. Computer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton. Organic Letters, 2015, 17, 2988-2991.
Additional correlations from DMSO-d6 data and analogue
Hydrogen deficient C30H18O14
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Naman, CB, Li, J, Moser, A, Hendrycks, JM, Benatrehina, PA, Chai, H, Yuan, C, Keller, WJ, Kinghorn, AD. Computer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton. Organic Letters, 2015, 17, 2988-2991.
1 in MeOH-d4 (400 MHz)
1 in DMSO-d6 (400 MHz)
Synthetic Product
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2. Lorenc, C, Sauri, J, Moser, A, Buevich, AV, Williams, AJ, Williamson, RT, Martin, GE and Peczuh, MW. Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation. ChemistryOpen, June 2015, 4 577-580.
O
OO
O
O O
O
OO
OO
O
O O
O
OO
O
O OH
O
O
O
OO
O
[O]
O
OO
O
O O
O
OH
mCPBA
1
34
dimerization
2
isomerization
ring-opening
5
reduction
?6
CH3
CH3
CH3
CH3
OH
O
O
O
O O
OOO
Expected
Product
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Lorenc, C, Sauri, J, Moser, A, Buevich, AV, Williams, AJ, Williamson, RT, Martin, GE and Peczuh, MW. Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation. ChemistryOpen, June 2015, 4 577-580.
Red arrow = 1,1-HD-ADEQUATE
With 1,1-ADEQUATE (40
Hz) & LR-HSQMBC (2 Hz &
4 Hz)*
Without 1,1-
ADEQUATE
&HSQMBC*
Isomers Generated 24970 64372
Time (seconds) 8 148
Top Candidate 1 1
*Data also includes: MF+NMR (1H,
13C, HSQC, COSY,
1H-
13C HMBC (opt.
10 Hz))
With 1,1-ADEQUATE data
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Lorenc, C, Sauri, J, Moser, A, Buevich, AV, Williams, AJ, Williamson, RT, Martin, GE and Peczuh, MW. Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation. ChemistryOpen, June 2015, 4 577-580.
TOP Structure
F2 Chemical Shif t (ppm) 4.80 4.75 4.70
80
85
90
95
100
105
1JCC Volume = 1.50
2JCC Volume = 0.16
The Fuzzy generator was invoked due to a 2JCC
correlation in the 1,1-ADEQUATE.1
1. M. Elyashberg, K.A. Blinov, A.J. Williams,
S.G. Molodtsov, G.E. Martin Fuzzy Structure
Generation: A New Efficient Tool For Computer-
Aided Structure Elucidation (CASE) J. Chem.
Inform. Model., 47:1053-1066, 2007.
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3. Xing-Nuo Li, Clark D. Ridge, Eugene P. Mazzola, Jianghao Sun, Osvaldo Gutierrez, Arvin Moser, Joseph C. DiMartino, Scott A. MacDonald and Pei Chen. Application of a Computer-Assisted Structure Elucidation Program for the Structural Determination of a New Terpenoid Aldehyde with an Unusual Skeleton. Magnetic Resonance in Chemistry, 2016, accepted.
TOP Structure
Natural Product - See Clark’s Presentation
Marine Natural Product
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4. Susanna T. S. Chan, Roger R. Nani, Evan A. Schauer, Gary E. Martin, Robert T. Williamson, Josep Saurí, Alexei V. Buevich, Wes A. Schafer, Andrew K. L. Goey, William D. Figg, Tanya R. Ransom, Curtis J. Henrich, Tawnya C. McKee, Arvin Moser, Scott A. McDonald, Shabana Khan, James B. McMahon, Martin J. Schnermann, Kirk R. Gustafson. Characterization and Synthesis of Eudistidine C, a Bioactive Marine Alkaloid with an Intriguing Molecular Scaffold, JACS, 2016, submitted.
Color in situ photograph of Eudistoma sp. (underwater)
Blue=COSY, Black=HMBC, Red=1H-15N HMBC
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Susanna T. S. Chan, Roger R. Nani, Evan A. Schauer, Gary E. Martin, Robert T. Williamson, Josep Saurí, Alexei V. Buevich, Wes A. Schafer, Andrew K. L. Goey, William D. Figg, Tanya R. Ransom, Curtis J. Henrich, Tawnya C. McKee, Arvin Moser, Scott A. McDonald, Shabana Khan, James B. McMahon, Martin J. Schnermann, Kirk R. Gustafson Characterization and Synthesis of Eudistidine C, a Bioactive Marine Alkaloid with an Intriguing Molecular Scaffold, JACS, submitted.
TOP Structure
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5. David R. Carbery, John P. Lowe, Arvin Moser, Dimitris Argyropoulos. Computer-Assisted Structure Elucidation of Two Isomeric, Highly Symmetrical Helical Molecules. EUROMAR, 2016 Denmark.
Synthetic Products
Expansion of HMBC data: normal 1H-{13C} HMBC (left) and band-selective 1H-{13C} HMBC (right) spectra of the first
isomer.
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David R. Carbery, John P. Lowe, Arvin Moser, Dimitris Argyropoulos. Computer-Assisted Structure Elucidation of Two Isomeric, Highly Symmetrical Helical Molecules. EUROMAR, 2016 Denmark.
Expansion of the NOESY spectrum of the second isomer around the region of the acetyl methyl signal at 3.70 ppm. The correlations to both
the aromatic rings are visible.
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David R. Carbery, John P. Lowe, Arvin Moser, Dimitris Argyropoulos. Computer-Assisted Structure Elucidation of Two Isomeric, Highly Symmetrical Helical Molecules. EUROMAR, 2016 Denmark.
7.417.487.74 7.627.65
NOESY_01.fid.esp
ppm 7.75 7.70 7.65 7.60 7.55 7.50 7.45 7.40
ppm
3.70
3.75
3.80
3.85
3.90
3.95
4.00
O
O
CH3
CH3
OCH3
OO
O
CH3
CH3
CH3
CH3
CH3
O
O
O
O
O
O
CH3CH3
CH3
CH3O
O
OO
O
O
First Second
6. Elyashberg, M. E. Moldtsov, S., Blinov K., Williams, A.J. J.Nat. Prod. 2013, 76,113-116.
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Liao, W.-Y.; Shen, C.-N.; Lin, L.-H.; Yang, Y.-L.; Han, H.-Y.; Chen, J.-W.; Kuo, S.-C.; Wu, S.-H.; Liaw, C.-C. J. Nat. Prod. 2012, 75, 630-635.
7. M. E. Elyashberg, K. A. Blinov, S.G. Molodtsov, T.S. Churanova, A.J. Williams.
ChemSpider Journal of Chemistry. 2009, 889.
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CH3
CH3
CH3
CH361.01
112.02
114.11
123.64
128.29
148.89
149.94
N
OH
O
O
O
O
O
O
OH
O
CH356.19
J. Nat. Prod. 2004, 67, 1168-1171.
CH3
CH3
CH3
CH3
N
OH
O
O
O
O
O
O
OH
O
CH3
11 12
14
7. M. E. Elyashberg, K. A. Blinov, S.G. Molodtsov, T.S. Churanova, A.J. Williams.
ChemSpider Journal of Chemistry. 2009, 889.
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CH3
CH3
CH3
CH361.01
112.02
114.11
123.64
128.29
148.89
149.94
N
OH
O
O
O
O
O
O
OH
O
CH356.19
J. Nat. Prod. 2004, 67, 1168-1171.
Recap: ACD/Structure Elucidator
Molecular WeightMS, IR, known fragmentsBad list
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Emily Mevers, Josep Saurí, Yizhou Liu, Arvin Moser, Timothy R. Ramadhar, Maria Varlan, R. Thomas Williamson, Gary E. Martin, Jon Clardy. Homodimericin A: a complex hexacyclic fungal metabolite. JACS, 2016, accepted.
CH3
CH3
CH3
CH3
OH
OH
OHO
O
O
O
OCH3
A
AOH
O
O
Case#1: The 2-hydroxy-3-methylbut-2-enedial fragment
was seen during the generation by ACD/Structure
Elucidator.
*Data also includes: MF & 5 mm cryoprobe NMR [1H (600 MHz), 13C (125 MHz), HSQC-DEPT (600 MHz), COSY (500 MHz),
TOCSY (500 MHz), and HMBC (500 MHz, ps=gc2hmbc)]
Case 1: Fragment Generation
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Emily Mevers, Josep Saurí, Yizhou Liu, Arvin Moser, Timothy R. Ramadhar, Maria Varlan, R. Thomas Williamson, Gary E. Martin, Jon Clardy. Homodimericin A: a complex hexacyclic fungal metabolite. JACS, 2016, accepted.
*Data also includes: MF & 5 mm cryoprobe NMR [1H (600 MHz), 13C (125 MHz), HSQC-DEPT (600 MHz), COSY (500 MHz),
TOCSY (500 MHz), and HMBC (500 MHz, ps=gc2hmbc)]
Case 2: User Fragments
?
?
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Emily Mevers, Josep Saurí, Yizhou Liu, Arvin Moser, Timothy R. Ramadhar, Maria Varlan, R. Thomas Williamson, Gary E. Martin, Jon Clardy. Homodimericin A: a complex hexacyclic fungal metabolite. JACS, 2016, accepted.
CH3
CH3
CH3
CH3
O
O
O
O
O
OH
OH
OH
dN(13C): 3.511
Formula: C28H26O8
FW: 490.5012
dN(1H): 0.341
dN(13C+1H): 6.922
1
CH3
CH3
CH3
CH3
OO
O
O
O
OH
OH
OH
dN(13C): 3.543
Formula: C28H26O8
FW: 490.5012
dN(1H): 0.345
dN(13C+1H): 6.991
2
Case 5: ADEQUATE Generation – Structure Known
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Emily Mevers, Josep Saurí, Yizhou Liu, Arvin Moser, Timothy R. Ramadhar, Maria Varlan, R. Thomas Williamson, Gary E. Martin, Jon Clardy. Homodimericin A: a complex hexacyclic fungal metabolite. JACS, 2016, accepted.
*Data also includes: MF & 5 mm cryoprobe NMR [1H (600 MHz), 13C (125 MHz), HSQC-DEPT (600 MHz), COSY (500 MHz),
TOCSY (500 MHz), and HMBC (500 MHz, ps=gc2hmbc)]
Case 2: Re-evaluated in 2016
249/28/2016
Solution: Introduce Free Structure Elucidation Tutorial Software
http://www.acdlabs.com/resources/freeware/teaching_se/
2015
Enhance your Elucidation Skills:Structure Elucidator Tutorials
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Arvin Moser and Brent G. Pautler. The fundamentals behind solving for unknown molecular structures using computer-assisted structure elucidation: a free software package at the undergraduate and graduate levels. Magnetic Resonance in Chemistry, 2016, 54, 701-704
Some Humor…
• I make bad chemistry jokes because all the good ones Argon
• Q: Why do chemists enjoy working with ammonia?A: Because it's pretty basic stuff.
• Q: What did one ion say to the other?A: I've got my ion you.
• Q: What did the chemist say when he found 2 isotopes of helium?A: HeHe
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