ABSTRACT

1’ number of nucleosides the method is not selective

._ msxJssI0~

.- :.

. ..-. .._. 1 _.: ._<.:_ _. :- .: . . :._ : ..‘....../ __;.: :

Mixtures of tkylphosphines with. carbon.: t&r&alides’ &e .found-- u&ful- for replacing both primary and secondary -hydroxyl ~oups~~~y’-~ziIos2~-~.~s and, in the absence of neighboring-group participation, invetiion’occurs at thecarhon atoms bearing a hydroxyl group’ 6. Although verification is stihlacking, it has been assumed .that halogenation with these reagents proceeds via the mechanism shovvn22; : :_‘:. . .

.:

Ar,P: .xcxs -i [Ar;P+-CX3X-]

ROH -.

As the reaction is generally performed at room or-. higher. temper&nres,: the

reaction was exa&ned to determine whether Some.measure of selectivity might-occur if the reactions were conducted at lower. temperatures.:. .- : : :. : ; : -. :._- . : _ ... : :. T

Initially, experiments -were .tried. with the readily available methyl a-D-glutxp pyranoside (1) in pyridine at 5O by the use 6f one molti e&ivaknt of both triphenyl- phospbine and carbon tetrachlo$de,- as 3mIicated in -.the projected;. mechanism. Pyridine was selected as the medium because of its excellent solvent proper&&and

CH2R’ OR

OH

rt;j -HO

OH

1 R = OMe.R*= OH 5R=OH

2R = OMe,R’= Cl 6R= cl

3R = OMe.R’= Er 7R= Br

4R = OMe,R’= I

8 R = ‘OH, R’= Cl (U anamer)

;

lOR.= Cl ::.,

: .‘. .:

‘. ‘,‘y;. -.. -- ..‘- & .._. -.

..

12 R = ,-,,R’= OH .: :_: ..-:_!6 : .iS .;, i3 R = H,R’& a-’

: .: ;. .... : ..; : _ . . . . ‘_ _; _ ::. ...I _. ._, : .- -.

_._,__ ,;;-,,- ,~:..; : .._. -.. .-. ,‘_ _“‘. ;- ..,, . . ,’ ;:::~ ,,.. :_,-_ .-:.... .: ;. .;-..:. .,..c __ .: -. -.. .r. :.,._ _ 1. ,_~ . . .

mmw oE._PRIMARY:-~~~__Gi(O~S -,-T::,:.; ._ -_'. ..' : '. r:j :.r; .f_: : :!: ;; '. :. .:; ;:_: :::_-_ :-5. _...,:x y: ... _;_';y:;: -:;I'__; :_:.::;, _,_ _ . . .i'.‘ ,. _. ,!. '_Z _,.. ..;., __:-._ __,

._'--93; ." ..:.: ..: : .-;.; >." .- -,.; :- .:_~ -.. r. A.‘.:: .; -: '. :_- (I. .",:_;I .--: :._

_, _..,_. _: .,

<i__,:.; .. ~_ ., ._ ; ..- ..; .I ..:_: -: :'., . . -y_ ._::__ ,.; . . ,- . . -,__y :-,, _.;'_,: i .: : ::.;,. : .-I:. ,:::::--,y

-.?ts v~la~ty.:T.J.c. ,of.the,&rix&eL.+th ~-~~vve_nt.;4,sho~~d’two_spo~,-cj~~ corresponding to_: &ethyl- :ti~h~~ro_~~~~~~~~~~~~~~~~~p~~~~idk( <&&&.& j&i :itaitinlg . .

I giy&&le- 1::: do@rmi~h~omatogr~pti~. r~~p~~~~b~~.~~~~~~~~~.~~* y, 49$&ld&l~; no: ~&&a&&rent &y&d or form~ation i;f~~.o~~r_~meound~~~~~~i;se~.~~~~~~~~l~~~~: -:- : -?..:_ __:_;.. ._

..:,~~r@t_$ron,-+rie+ JIoweve@f the proportion of “@iph&&lph&phi& ;uas ;ch&ged ‘to:. :‘i$o r$~.e~qu@&lent& kn$lmost quan~titative yield of.2 ~$a_sob&iued; kniilar results :.._-- .,,, ._ wer~‘also ob@ined:at higher-temperatures, at 65“ the~halogenatki .was selective and ~c&q$&,~$~ 3 f&&_ _I:;, -. _‘<- ‘.:. ..~ _‘.T AZ

._- . . : &b~_&~ti6n~ _&peii@e& :-&ith. &bon tetrabromide o’;‘:‘ca&on &&di& &.

g+& di”&rbon’tetr&loride gave met~y~6-l;ro~~.-tioxy~~-~~~~p~a~~si~e (3), and methyl 6-iodo-6;deoxy-&~~-glucop~o~ide (4),~&pe&ively. In these h&gen&

tiouie~&ior& the $forementioned sel&t@ity and &p&den& of yield on the. propor:._ tion. of, triphenylphosphirie in relation:’ to carbon tetrahalide was observed (s& Table $?J’hese results &lea& demonstrate that combinations of two molar equivalents of .ti!iphenylphosp&e .tith one.mol& ‘equivalent~of carbon- tetr&lide :&I -pyrk&e are: exkllent reagents .for the selective h~logenation of primary hydroxyl:groups. It is further .evident .&at, in py&Iine at least, halogehatidn with these reagents proceeds bjr a &chaqism: _ch@rent from that .%&ten earljer. A ~more$robable:.~ourse for _

halogen&on might be via the initial formation of:a tr!iphenylpho&phine.dihalide 19 F., = -Cl,. Br, .or I)- to. produce a bulky halogenating complex involving the’solvent:

21;h,P +. CX, _+ Ph,PC=X;+ :Ph,PX, C5H5N . . : .. “ :. ‘:.RcH,oH

I. ., + -,’ .-. Ha~ogenatingcomplex .w... . . _ .-_ -.:

.- BCH;X

{. -The formation of I9 (X -= Br)from the-reaction of 2 niol of triphenylphosphine and one mol of: carbon tetrabromide :is known”, and the :usefulness of triphenyl- phospbine.dibromide as a reagent for bromination. through complex&ion~~tith N,N- dimethylformamide has beenreported2’.: .‘ :. :. . . . --. .[:, I ; . . -.

: -:; .:.I To determine the: general usefuhuzss. of. the. halogenation -pro&lure, it was

exteuded to. a v&ety .of polyhydroxy -cornpour@. .Each compound ekunined could ‘be converted into the primary hahde in excellent yield, provided-optjmum proportions of:the 1 .xa&ant.s were. used: :The : n.m.r;:: spectrum : of 6-chlor&6-deoxy-i,2-O-iso- propyhdene-ol-D-@usfsa.nose: (6); obtained- as, ? q&w.e solid. from-the chlorina_: ti& ,of.l,2-d-isopropylidene-a,D-gIiicofiirans~ .(s)_sho~.d.~:the.H-l,. .H:?;-. and -H-.6 ‘@a ‘an+, p) sigr&&s.doublets (Jr ;Z .3.5.%@~,. J&,-3 Hz)_af~;z 4;!2;. 5;52;$nd:.6;22, ~:_respec~v~ly, end the two. sets. of ‘methy~.pr~tdns:_gave-peaks: at z 8.57 and : 8.6L.The foregoing p&.r.-spe$$~parartietei$were ~onsistent~~&th stn&ure. .6;.&i&ese data

:resembi~th~recdrdedvalGesf6rsinlilarlyconstitutedI~~~29.ThetiTi;;hy~~~~l resor&.t$es .&p$tied. at:+!2 and-685 .and d+ppeared -on ‘~x~h~ge.with:d~.~terium.

:.’ ~~~~~.~~~~.i~.~.f~~ strutitu$.6 $asprovided- by hydrolysis $ith aqueous &lfuric ,- ~~at+k;.tqi-,$he~~ knoSvn;-8_chlaro~~eoi~~~~.; (8) j-::The’ ri.mir.~+k&?um .-of : 6- -_~~~~&-a~~_i;2~~_~~~~~~~~dene_~~~~~~c~~~~~~.~~~~;:. &o :. &j&&j; ,a’. -i- ,,.~&~&.&~~~~ co& ~~~howe,wwwwwwwwwwwwwwwwwwed f&k= ~~~.~to:tli6se:foi_~.~~~~~ts .&&L+.&.&

. . :.. :’ :-‘._:._!:.:-- ..: -_:--; . . . ‘: T -._, . . . . ;. .::1_.._.. __ _..- .‘,-_.; ;,. .,, :L,

1 1 :.

t

i

: 5 9

12 15 15 16 16 17

‘cc4 cc4 cc4 cc34 ccw

cBr4

CBr4 CL

zJ4 CBr4

ccl4

CCI4C

ccl4

CBr4

Cal

CC4 ccl4

: 18 E : -.:; ; ._‘..4!I- -_.: :.

. . _

25 .18 -_ :E.. 1.;. Y2 -. 98

65 5 I:“.. 60 0.2. 25 18 25 18 .-I!- -4. 97 ::- 5 20 .F

Oh ._ __ :_ 6 96 -:

-' 60 F 7:. 9s 65 0.2 .I0 ..-:94-- 70 2 :g2. .,.

60 I -F 6 _.75 :, ;. 60 1 .F 7 .80

.l No ma&ok 18 Noreaction .. ‘.

25 18 E 18 : 92

S2e Experimental section. 52 mol. “15 mmol.

are identical to those recorded for a sample of 7 prepared by a different route3’. The ready preparation of 6 and 7 in high yield is of considerable synthetic importance because 7 (and possibly 6) is the precursor 32 for 5,6-anhydr&l,2-O-isopropylidene-cr- D-glucofuranose (13), which itself is a valuable intermediate in synthesis33. ’

5’-Haioribonucieosides are useful precursor for the synth&is of nucleotides34; anhydronucleosides3’, sulfur anaIogs’ 6, deoxynucleosides3’, and cobalamin ana- logs=; introduction of a haIogen atom at the 5’-position. is therefore. of’ paiticular importance. Previous attempts3g to prepare 5’-chloroinosine :(lO) by the hydrolysis of S-chloro-5’-deoxy-2’,3’-0-isopropylideneinosine (11) : resulted .in ; the.: formation of a syrup-for which no anaIytica1 data or physical constants were gi&i:kIowever, by using the present method,, cjstalfine 10 was obtained in high yield- by- diiect dhlorina- tion of inosine (9)_ SimilarIy, uridine was c&verGd into -the-know~--~‘-c~o~~~5’; deoxyuridine 24 _ The n.m.r. spectrum of 10 -showed the~anomen’c-proton &gnai zis a : - doublet at z 4.12 (J, ,2 5.5 Hz), the H-2’ signal as a trifilet tit 7 5.4 (i2;$6.5 H@iand .the H-2 and H-8. resonances at T I .8 and 2.0; respectiyely; Conclusive: proof:$jr : the location of the. chlorine atom was. obtained .by prepa&g 5~chl&LS~de~xy-~ ;3’_X isopropylideneinosir (11) by the reaction of IlO- with ac&ne~$c@aining j-toluene-~ sulfonic acid and 2,2dimethoxypropane. . . Urider’ these cd&&~, tJie j&Ad of ~17 was high, but no reaction took placeif 2,2dimethoxyproparie.‘was excluded from-the : mixture.

.-. :._:--

.. There has been considerab+zcent interest in the .&&e&of &rc&se.deriva&~ :.

: .,.&&:. :. _, -. : -

ceMBNT.O~~~~~~~~~L.GROupS‘~.'_~~~ 1. .‘_I .: .. :;.I f:: :, ._ .. .$15: :. ,-

: -.:

-: ,.. -: -:

.‘m~&i ‘~a~j~~~~~+i&i& :&&ions 40; :Prepadfion :of halogeno’~&ivatives r-has been -.’ ~~~~~..-~~~~_is~p..reacti~~~il. :&d&-$n&&~?‘?‘;4? @at, ., of & .&ee :-primary ~S+&$ i *&j&s C&l& ,r;l& .m&&::+& & t&k. &;&_p&tio~~ &an & &i : i ‘..&&io*_ 1

-“It ,wti-titicipat&l -thet, .by thepresent method;:.the -reaction .ofz&o~~~(l2) with ‘triphc3nyl~_hosphiiie.tteti?~~oride in pyridine’might .effect -chl~rinatidn’it- the, .-6.&i+ .fj’ i;@siti&@.‘-Thi s‘e~@&atio~-was borne out when- 6;6~~di~~o~o_6,6’~.~d~xy;. ‘sucroSe;(13) km obt+ined iu high yi~ld.-~Th’e.easy,.one;~~p preparation of 13 qfferi a

&up& .route:for’ Prepara;tion ‘of other sucrose ~derivative&&odified at the 6 &rd..6’ posi&ons.;These kesdts furtherindicat‘e-that the @log&rating species inight be quite

bulky, thus preventing halogenation not only of the secondary..hydroxyl.groups’but also of the primary ll’-position: The physical constants of 13 audits ‘hexabenzorjte 14 are in. agreement with those recorded4?b_. . . : .. _ :- : ;. .‘I :

.- Is&Sand Kirkpatrick reported+? the formation of cis-1,2-dichlOro &mpounds from the reaction of epoxides with triphenylphospmne in carbon tetrachloride.. It is assumed that the ‘epoxide ring is opened by the chloride anion of -Ph,P?CCl,Cl- (initially formed from tiphenylphosphine and &rbon tetrachloride) with simultaneous bond-formation between the epoxide oxygen atom&d phosphorus.

To’ examine whether the course of. halogenation of- oxiranes .-by. triphenyl- phosphinmbon tetrahalide reagents is influenced by solvents, $6-anhydro-1,2-o- isopropyiidene-a-D-glucofuranose (15) was treated separately. in pyridine. -tith tri-

phenilphosphintibon te_trachloride and triphenylphosphine_carbon tetrabromide. From these -reactions, 6chlorod;deoxy-l,2-O-isopropylidene-cc;p-glucofuranose (6) and 6-bromo-6-deoxy-1,2-O-isopropylidenelcr_ose (7) we& isolated in high yield. : .’ -.

The results indicate that halogenation of the epoxide with triphenylphosphine- carbon .tetr~halide in pyridine does not follow the’mechariism suggested?3. Had it done SO, elimination of. the epoxide. oxygen atom would be expe&d, in view -of the strong afbnity of phosphorus-for oxygen:,The products 6 and .7 are possibly formed from 15 through nucleophilic attack by.a halide anion atthe steric,aUy available C-6 without bond’formation between.the epoxide oxygen atom and.phosphonis. -. . .

Previous. efforts to .halogenate --the 3-hydroxyl . group. of- 1,2 : $6~di-O-iso- ‘propylidene%-D-glucofuranose (16) by the use of triphenylphosphine-based reagents have led to,acetal migration;.culminating in the formation.of 6deoxyi6ihalo-1,2:-3,5- di+isopropylidene a-D-glucofura’noses1g,~3,2~;-T o examine if a&&migration would take p&e under the present halogenating conditions,. i8 was treated with triphenyIt pl@&hi~_ P&h carbon tetiachlo.tide. Thin~layer chromatograms of re&$.ion mixtures.. with ;20 : 1 i chloroform-acetone showed;.io ‘change in. 16, and :thus not. migration of a+&al groups occurred under the conditions chosen. . i. ‘-’ .. -’ : :

.; _;- ‘: :

,6&-T&,:; .._... :-.: .._ - _. . . : ,_; -: : 1 .-.. .__: ,:.; ,; ’ ~, , ‘.-- : _- .-.. _‘.I .:

.: t. :_.. F. :: .- -

:I ‘. G&&d methods;- i. Purity ofproducts was d&em+& ybi &o.. err ‘da&s. plates

~.&@$d~svith sil& gel GF-254 (E; .Merck;--Darmstadt, Germany) ‘~d~irrigated with A;

516.. .-. ._- ‘-. A. :Iii ti:-ANIsilZ zAMAN;:.R,i&JH&& : I, .- ., : :_ .:. . .

'..

6 : l- &loroform-methanol, B, 9.: 2 chloroform~a~tone, c, .145_5’i3 &hi! .a&&& ethanol-water, and. 0, :. 20 :.l cbloroftirr&aet&e. ‘- Com@onents ) were _lo_gat@; by.. spr&ii& the plateswith 5 ?A sulfiuic a@J in ethanol_.aud-heat@@ or’byvietig umler a _

short-wavelength u.v. lamp.~.ColUmn chromatogiaphyY:was performed on- sihcagel. powder- (.J. T. .&ker chemical. Co.). Columns were eluted.witb -Es: 20 :.i.chlorofoim~ methanol,. r;, 6 : 1 chloroform-acetone, G,: 3 : 1’ hex&z-ethyl acetate,-. _@d C. ‘Opt$al rotations were measured with a -Rerkin-Elmer-. model- 141~ .po@meter ami .n.m.r.- spe&ra were @corded with a Varian T6OA spectrometer v&h te@n&li&&ne. as the internal standard. Evaporations :were conducted under-. din&&bed. p&sure -&i& q

bath temperature below 40”. General procedure. - The polyhydroxy compound v&s dissolved yin ~yridin~

(0.1 g/5-10 ml) by stirring at 25” or at boiling tem$eratur&Thesolutiou was cooled to 0” and triphenylphosphine was added, followed by the:addition at 0” of carbon tetrabalide in several portions. The resulting mixture- was--protected- from moisture and stirred where precipitation occurred. After keeping the- mixture at. the :desired temperatures for. the required -length of time, methanol, (i0. ml/l_- g. Of. hydroxyl com- pound) was added to decompose any excess of reagent. Solvent was removed by

evaporation and the residue was chromatographed on- s&a gel. Non-carbohydrate material was removed by elution with chloroform, and further elutionwith C; E, or F gave the pure halogen0 derivatives. Data related to the proportions of the reactants, yields of products, and reaction conditions are given in Table I. -. . I

Methyl 6-chloro-6-deoxy-u-D-glucobyrarzoside (2). 1 The glycoside -2 was a white crystalline solid; m.p. 11 l-l 12 o after crystallization from chloroform-hexane; [a];* f153” (c 1, methanol) (liL4” m.p. l10-112°, [cc& fl39” in water). : ..

Methyl 6-bromo-6-deoxy-a-D-g2ucopyranoside (3): -. The- glucoside 3 ‘was a white solid, m-p. 130” after crystallization from chloroform-hexaue; [cz]g5 ,+125:2O (c 1, methanol) (litP4 m.p. 129-130”, [a& f107.40 in water). ._

MethyZ 6-deoxy-6-iodo-a-D-gZucop)iranoside (4). - The glucoside-4 W& .awbite solid, m.p. 148 o after crystallization from chloroform-hexane; [alis -+107.8-” (c- i; methanol) (lit.45 m.p. 148” [aIn +99.” in water). . . I

6-Chlo?o-6-deoxy-I,2-O-isopropylidene-u-D-g~u~ofur~ose. (6). - Compound 6 was obtained from 5 or 15 as a crystalhue solid,. m.p. SO?- after crystallization from ether-hexane; [a]gs - 11 O (c, 2, chloroform); n.m.r. in-CDCI, see:D&cussion. _.

Anal. Calc. for CgH&105: C, 45.29;. H, 6.33;. cl, 14.85. Found:: C,.-45.17; H, 6.51; Cl, 14.69.

6-Chloro-6-deoxy-D-glucose (8). - A mixture of:6.(240 mg).tid i5.&:of&&-. sulfuric acid was stirred .for 5 h at 700. ~T.1.c. .&th solvent &&i&ted.~,compi&e. conversion of 6 into 8. The acid was neutralized-with,lR45- (OH?-),&sin andL%.be mixture was filtered. Evaporation of the filtrate gave 8. (18O.‘mgj:-G ?:synip that 1 crystallized on keeping. After crystallization from etba.nol; 8 had,m.$; -137”; i [a]g.

+ 96 + +51” (20 h, c 1, water) (lit.3o m;p. !35&6?, [a],.95.8. +:5l~l”‘ixi~tiaterj; ..

.6_Bromo-6-deox~-I,2-O-isopropyiidene-cr_ .-(-i)$‘+. ~m$&i~~ 7

wasobtained from 4 or 15 as.a whitecry&lline-solid, ti.pi 8-Z z&e> c?jddl.&kon~ -. -.. . .

: ‘Anal.‘Calc,lfor~~lbH;1Ci:NkO*:.Cj-’41;89; ,H, 3.87; Cl; ii.??? N;.-l9.54..Fo@$ C, 42.10,‘H, 4;-l@, ~2.~0;_~;~~~.30~-~~ .’ “: : .: -. : :‘.; ,. ‘i .!’ --,.:>, ;.:-. .: .‘, .:

: - 5~-chZOro-5’-deo~~2,3-O~i~o~~~~~ZZ~~e~~~~i~~’.. (li). y xi &tuh.~.o~..~~O (140 mg) in 30 ml of acetone ~orrt$r&g @-tofuenesulfoniti; acid (1001mg),&nd:~2,2- d&etboqproBane.e._(~5 ml). was stirred for 2.b -at: 25-Y. T.l.c..$ith sOlvent C.indicz&d complete. conversion bf 10 intO 11; p-Toluenesulfomc a&id. was ne&raliz& wit&

. ti excess of sod&m hydrogen&bon& and ,the flfixture. was :filtered.-Ev&or$ion -.

of the.@trate g&e il(l4O:mg,~87.5 %) as a &yst&ine solid; m.$20! 0 after q$talhx& tioix from-methanol (lit.24 m-p. 201-20l.S:j.. :

Mthe absence +,2,2-dimethoxypropane, -the foTego.mg reaction did tiot occur. 5~-Chloro-51-d~~~~u~i~~~~ (is). 1 The chid+ .compoun$ $8. obtained from i7

had m.p. 172-174” .(lik’? m.p; 170-;172”). -.. .‘:. -. ;. _ : ..

6,d’-Dichlor&6,6’-dideoxyT+crose (13). ; Ttie- d+hl6ro derivative .i3 c+aipkd from sucrose (12) had m.p1.82~.5~ afik~~&+aI@i~~.~‘f~~~ butanon&; [a]ii +60_” ._: (c 1; water) (liL40b m-p. M-88”. [ali f60” inwater). :- ;

?,3,4,~‘,3’,4’-Hexn-O-beF~zoy~-6,6’_dichlo~o~6,~~dideoxy~cr~se:(l4). - Benzoyl chloride (5 ml) was added to a solution .of -13 .(190 mg)m 20 ml Of py$lixie. After keeping the -&xture for 40 h at .25O, solvent .was rem&ed. by -evap&a&n. ‘The syrupy residue was treated with saturated sodium by+o;genybouate- solution -and extracted with chloroform.rEvqora&m of the: diie$ extract-&e a syrup that I&s. purified by chromatography ,on silica gel. : Eluti& with. 20 : 1. hexa&ethyl :aeetate separated the non-carbohydrate material; Further.ehition witbsolvent G gave pure 14 (400.‘mg,:$O%);: m.p: 88_S9” .after. ciyst&lization from .et@&l; [&Is:’ +5;7” <c 1, &lorofprm) (lit.‘? m-p. 81_87O, [&)zs +5.8? in&lor&form); .:‘- : ..

&al. Cklc. for Cs.&H;&l&& C, 64.83; H, 443; Cl, 6.89. Eound: .C,i64.71;- JIJ, 4.71; (-1; 6.99, ._ - : .--. .: ._ :

.._ _-.

I ,_., : _wcpJ :

.-

1 J. E. G. Bm, Adv. Carboiydr. Chem., i2 (1967) 177-227. 2 -A. H. Hmm, Adv. Cmbolrydr. Ckm. Bioch@., 33 (1976) ll%i ..

.- 3 c-w. CHfrJ ANDR L. WEIISTLER, J. ‘Org. Chem.,. 28 (1973) 832-834. ~~:~4B;kLAwm~,$V.kSzmtrx, AND J. K. N..Joms, Chem. Cimmun.,.(l969) 787-788. ... 5 :B. T. LAWiON;W;A. Sz&m;AND 3. K.:N. Jom;Carbohydr. Re+, 14 (1970) 255-258.

: 6- R G. iiLhfQ= ti E.-i Xmsr; ‘Cmbohvdr, Res.; 46 (1976) 3-l; i: hi> J, ICOBII$;Y.‘FO~~O~, ti k; .M&GEL, JI-Org. chap;39 (1974) 1564+70.

.8 B. J:Mi&szrk ,-TptraliedrcnLett.,~(1970)‘33_36..: ‘. -1.:; :_ :. ‘. ._ .9 B. we+; 54 (1921), 1082_1084; : . : ‘-. . . .lO.A;-Khmi y;G. Iv&at&q Ctibhyd~. l&s., ?;(197& 425431. .:: ’ :.-

:

111-129. . . -.. & J.B. I& AND I. M. Do& Tetrahedron, 23 (1967) 359-3. .. .’

I . . _ ;

23 C.’ R. HA YLOCK, 375-382.

L. D. hlEiMN, K. N. SLEssod;.4ND -A. S. T”t”; &.r&hy&_--&z&,:16 (1971). _ -.. : : _, ;

24 J. P. H. Vv EN AND J. G_ MODAL, J. Oe..Chem.;37 (1972) 2289-&?&k ; 1 :_.. : _

25 EC. EIAGA,M_ Yomuu WA, AND T_ Kxx-o, .BI$ Chem. &c. JPI+, $f(1976) 3922-3924. 26 R_ G. WFZZS AND E. I. SNYDER, J; Org. .Chem., 35 (1?70)_1627-!632; p. BREH_~ I. M. Do&&

J. B. z.FE, AND M. F_ S. MATOUGH, Gem. Ind. (Lanrion), (1969) 1017-1718. : --.L : .-. 27 F_ R~IREZ, N. B. D-, AND N. MCKELF, J fen. C&m. Sec., 84 (1962).1745-1747.. 28 R K. BoEcKMAN AND B. GANEM, Tetrahedron Left., (1974) 913-916; M., E. H%RR AND R. A.

JOHNSON, J. Org. Chem., 37 (1972) 310-312. ‘. .29 S. HAMssIAN AND N. R PLESSAS, L Org. Chem., 34 (1969) 2163-2170; -.: 30D_C.C_Sw,J.Chem.Sec.,(1956)1244-1247. ... . . . . ..: -. 31 K. FRE~DENBERG ANIY G. UTEJZMAEIN. Fer., 52 (1919) l&%-1513.

. .

32 K. F~TJDENIERG, IX TOEPFER, AND C. C. ANDEI~~ON, Ber., 61 (1928) 1750-1760_ ’ -. 33 R_ D. G’LPFHRIE, in W. PIGMAN AND D. HOR-A-CIN @ds.), Tk carbohydrates, 2nd edn..:VoI. IA,

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