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Reprinted from:METHODS IN CARBOHYDRATE CHEMISTRY, VOL VII

General Methods, Glycosaminoglycans,and G!ycoproteins 1976

ACADEMIC PRESS, INC.New York Son Francica LottO-

THIO SUGARS[8) Thio Sugars from Oxidatively Coupled Xanthates

By B. S. SHASHA, D. TRIMNELL, E. 1. STOUT, AND W. M. DOANENorthern Regional Research Laboratory, U.S. Department

ot"AgriclIltllre, Peoria, Illinois

(III)

(IV)

36(v )

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[8] THIO SUGARS FROM OXIDATIVELY COUPLED XANTHATES 37SII

....---COCHzIS - C O C ~ HIISOMe oIO-CMez

(vI)

/ SCH.S=C I " O C ~ H

OMe oIO-CMez(vII)

l,

(IX)

IntroductionOxidatively coupled sugar xanthates, known as dithiobis(thioformates),

decompose to thio sugars containing O,S-dithiocarbonate groups. Thiolationoccurs at either primary or secondary carbon atoms in the sugars with eitherretention (1) or inversion (2) of configuration. The choice of decompositionconditions depends upon the structure of the oxidatively coupled xanthateand upon minimizing alternative decomposition products, such as thionocarbonates (Vol. VI [77J). Cyclic dithiobis(thioformates) derived from vicinal

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38 MONO- ANO DISACCHARIDEStrans-diols decompose upon pyrolysis or upon treatment with methyl sulfoxide containing catalytic amounts of base to give cyclic O,s-dithiocarbonates with accompanying inversion at the site ofthiolation (2). Decompositionis greatly facilitated when a primary carbon atom is included in the dithiobis(thioformate) ring or when the ring is attached to positions on an acyclicsugar. Some are so reactive that dissolution in acetone at ambient temperatures causes extensive thiolation (3). Photolysis induces thiolation withretention of configuration (1) in some acyclic dithiobis(thioformates) whichdo not give thiolated products on pyrolysis or solvent-base treatments.

Procedure

Preparation of Dithiobis(thioformates)The following example is typical for the preparation of all dithiobis(thioformates) (4):Methyl 4,6-0-benzylidene-'l.-o-glucopyranoside (1.0 g) in 1.0 ml of methyl

sulfoxide and 1.0 ml of carbon disulfide is cooled to 5: and stirred rapidlywhile 0.8 ml of 12.5 N sodium hydroxide is added. After 5 min, the mixture isdiluted to 100 ml with 0: water, and 1.0 g of sodium nitrite is added. A streamofnitrogen is passed in rapidly, and the solution is acidified with 10 ml of 5Nacetic acid. After 15 min, the precipitate is collected by filtration, washedthoroughly with water, and dried. Cyclic dithiobis(thioformate) (I) is obtainedin about 5 0 ~ ~ yield when the crude product is extracted with acetone and theacetone extract is evaporated or cooled (2).AfetIzy/ 4,6-0-Benzy/idene-3-tlz iO-'l.-o-a//opyranoside 2,3-DitIz iocarbonate(II) (2)

MethyI4,6-0-benzylidene-'l.-o-glucopyranoside 2,3-dithiobis(thioformate)(I) (2) is washed with 1:20 vIv sulfuric acid-ethanol for 1 min and rinsed withethanol until the washings are neutral. The dried compound (2.90 g) ispyrolyzed at 240: for 5 min. The mixture is cooled and extracted with chloroform, and then the chloroform extract is filtered.

After the filtrate is adsorbed onto 100 g of a 9 : I w!w mixture of silicic acid(lOO-mesh)-activated carbon, it is eluted with 500 ml of 1:9 vlv ethyl acetatehexane to remove sulfur and unreacted starting material. Subsequent elutions with 250 ml of 1:4 vlv ethyl acetate-hexane, 500 ml of 3:7 vlv ethylacetate-hexane, and 250 ml of 2 :3 vIv ethyl acetate-hexane remove persubstituted dithiocarbonates and thionocarbonates. These eluates are combined,and the solvent is evaporated. The residue is dissolved in 50 ml ofethyl acetate

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[8] THIO SUGARS FROM OXIDATIVELY COUPLEO XANTHATES 39and shaken with 10 ml of 12.5 N sodium hydroxide solution for 5 min todecompose the thionocarbonates. The ethyl acetate solution is neutralizedby shaking it with dilute acetic acid and dried with anhydrous sodiumsulfate. Evaporation of the solvent leaves a residue which is readsorbed onto40 g of silicic acid from chloroform solution. Elution with 200 ml of 1:9 vlvethyl acetate-hexane removes a minor. less polar dithiocarbonate, and subsequent elution \vith 500 ml of 3:7 ethyl acetate-hexane removes the majorcomponent which is obtained crystalline upon evaporation of solvent;yield 0.46 g ( 2 0 ~ ~ ) ; mp 183' 184' after recrystallization from ethyl acetatehexane; [Cl.J230 +281' (c 1.2, chloroform); "ma,lilm 1060,1190 em-I [O(C=S)S]: }n""chloroform 285-286 nm (8 15,150): nmr in pyridine-d5: r 4.95 (i-protondoublet, J 1.2 5.3 Hz, H-l), 4.32 (I-proton doublet of doublets, J 2.3 6.8 Hz,H-2), 4.72 (i-proton doublet of doublets, J3.4 5.0 Hz, H-3), 5.78 (I-protondoublet of doublets, J4 .5 9.0 Hz, H-4).1\1cthyl 4,6-0-Bcnzy/idcnc-2-th io-Cl.-o-mannopyranosidc 2,3-D i thiocarbonatc(Ill) (2)A mixture of 1.0 g of I in 3 ml of methyl sulfoxide containing 0.06 ml ofdicyclohexylamine is heated at 140' for 3 min. After most of the gas evolution

ceases, the dark mixture is poured into 100 ml of 0' water, and the resultingsolid is collected by filtration and dried in air. The solid is dissolved in 5 ml ofchloroform and adsorbed onto a 4.5 x ll-cm column of silicic acid (100mesh). Elution with 1 liter of hexane removes sulfur, and then elution with250 ml of 1:9 vlv ethyl acetate-hexane removes colored impurities. Subsequent elution with 500 ml1:9 vlv ethyl acetate-hexane desorbs III, which isobtained crystalline upon evaporation of solvent; yield 0.35 g ( 4 7 ' 1 ~ ) ; mp153' -ISS: after recrystallized from ethanol: [CI.J25 0 - 79' (c 0.9, chloroform);"ma,lilm 1060, 1200 em -I [O(C = S)SJ; ), ma/hloroform 282-285 nm (8 14,200); nmrin pyridine-ds : r 4.97 (I-proton singlet, J 1.2 0.0 Hz, H-l), 5.19 (I-protondoublet, J2.3 7.0 Hz, H-2), 4.39 (i-proton triplet, J3.4 8.0 Hz, H-3).1,2 :5,6-Di-0-isopropy/idcnc-3-tlzio-0-altritol 3A-Dithiocarbonatc (V) (2)1,2 :5.6-Di-0-isopropylidene-o-mannitoI3,4-dithiobis(thioformatel (IV) (2)(1.0 g) is kept in a mixture of 2.0 ml ofmethyl sulfoxide and 0.04 ml of triethy

lamine at 25 ' for 3 h. The mixture is poured into 100 ml of 0' water, and theresulting solid is collected by filtration and dried in air. The solid is mixedwith 80 ml of 1:1vlv carbon disulfide-hexane. The solution is passed througha silicic acid 4.5 x II-em column. Elution with 500 ml of 1: 1 vlv carbondisulfide-hexane removes sulfur and impurities, and elution with 500 ml of50: 1 vIv carbon disulfide-ethyl acetate removes V. Evaporation of solvent

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40 MONO- ANO DISACCHARIDESleaves V; yield 0.72 g (93%); mp 141 -142' after recrystallization fromhexane: [et.] 240 - 94' (c 0.5, chloroform); \' max film 1060, 1200 cm I [O(C = SiS] :). 11""clhanol 283 nm (c; 12,000); nmr in carbon disulfide: "[ 6.47 (I-proton doubletof doublets, J2.3 8.5, J 3.4 6.3 Hz, H-3 at position of thiolation).1,2-0-Isopropylidene-3-0-methyl-6-thio- -o-gilicofilranose5,6-Dithiocarbonate (V II) (2)1,2-0-isopropylidene-3-0-methyl-et.-0-glucofuranose 5,6-dithiobis(thiofor

mate) (VI), prepared from 4.0 g of 1,2-0-isopropylidene-3-0-methyl-et.-0glucofuranose (3), is too reactive to be isolated. When VI, initially a brownsyrup, is dissolved in acetone, gas (carbonyl sulfide) evolves and sulfurprecipitates. After 15 min, the decomposition is complete. Product VII ispurified by desorption chromatography on silicic acid (lOO-mesh) or basicalumina (80-200 mesh) \vith hexane-ethyl aceta te as the eluant and isobtained as a syrup; yield 3.0 g ( 6 0 ~ ; ~ ) ; [et.]o -43 ' (c 2, acetone); vma,film 1060,1090 cm- 1 [O(C=S)S]; )'max"lhal1oI283 nm (c; 17,000); nmr in carbon tetrachloride: "[ 4.23 (I-proton doublet, J 1.2 4.0 Hz, H -1) 4.80 (I-proton apparentquartet, H-5), 5.5 (I-proton doublet, H-2), 5.70 (I-proton doublet of doublets, rH-4), 6.18 (I-proton doublet, H-3), 6.32 (2-proton multiplet, H-6, H-6'). IBis (3-deoxy-1 ,2 :5,6-di-0-isopropylidene-et.-0-gllicofilranos-3-y/) 3-0,3'-S-Dithiocarbonate (IX) (1)Bis(1,2:5,6-di-0-isopropylidene-et.-0-glucofuranose) 3,3'-dithiobis(thiofor

mate) (VIII) (2.5 g) in 230 ml of cyclohexane is irradiated under nitrogen for20 h with a Hanovia 450 w, (Canrad-Hanovia, Newark, New Jersey)1 highpressure mercury arc lamp with a Corex filter in a quartz immersion well.The volatile components are evaporated at room temperature, and theyellow syrup is chromatographed on silicic acid (lOO-mesh) with acetonehexane as the eluant. After sulfur and other impurities are desorbed, IX isrecrystallized from hexane; yield 0.92 g ( 4 3 ~ ; ' ; ) , mp 133'-135': [et.]230 -56 '(c 1, acetone); I. ma ,Clhanol282 nm (c; 9,600); nmr in chloroform-d: "[ 4.15 (3proton multiplet, H-1,H-1 ',H-3'), 5.31 (2-proton doublet, H-2,H-2'). Similarly,bis(1,2 :3,4-di-0-isopropylidene-et.-o-galactopyranose) 6,6'-dithiobis(thioformate) can be converted to the corresponding 6-0,6'-S-dithiocarbonate in7 8 ~ o yield. These transformations cannot be induced thermally or in solventbase systems, as either other decompositions take place or symmetricalthionocarbonates are formed under these conditions.

1 The menlion of firm names or lrade producls does nOI imply that they are endorsed orrecommended by the Department of Agriculture over other firms or similar products notmentioned.

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rI

[8] THIO SUGARS FROM OXIDATIVELY COUPLED XANTHATES 41References

(I) E. 1. Stout. "Photolysis of Some Carbohydrate Dithiobis(thioformates),"' Diss. Abslr, 34.3715-B (1974).(2) B. S. Shasha, D. TrimnelL and W. M. Doane. Carbolzyd. Res., 32. 349 (1974).

(3) B. S. Shasha and W. M. Doane. Carbolzyd. Res., 34, 370 (1974).(4) B. S. Shasha. W. M. Doane. C. R. RusselL and C. E. Rist. Carbolzyd. Res.. 7, 99 (1968).

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[9] Thio Sugars from Cyclic ThionocarbonatesBy D . TRIMNELL AND W. M. DOANE

Northern Regional Research Laboratory,U.S. Department of Agriculture, Peoria, IllinoisO -CH

s=1 ~ 0'\ OMeo OMeOM e

/OCH 2s=c I' O C ~ HOA e oIO - C M e 2

(ill)

/ S ~ C H 2o=c

'\ OM eo OM eOM e

(II)

(IV)

IntroductionCyclic thionocarbonate esters (Vol. VIII), w'hich include a primary

carbon atom of a sugar, undergo isomerization to cyclic monothiolcarbonates in the presence of potassium iodide in acetonitrile (1,2). Thiolation occursat the primary carbon atom, an d yields of the thio sugar derivatives are from50 to 8 5 ~ / ~ .

Procedure

Methyl 2,3-Di-O-methyl-6-thio-'l.-D-glucopyranoside 4,6-Monothiolcarbonate (II) (2)A solution of 0.5 g of methyl 2,3-di-O-methyl-'l.-D-glucopyranoside 4,6

thionocarbonate (I) (Vol. VIII) in 20 ml of acetonitrile containing 3 g of42