The Preparation of Some Mercapto Monosaccharides

Abstract

Methyl 4,G-O-benzylidene-2-be1izylthio-2-deosy-or-~-altropyranoside and methyl l,(j-0-benzylidene-3-benzylthio-3-deoxy-or-~-altropyraosid have been prepared by the reaction of sodi~tlu benzylmercaptide with methyl 3,3-anhyclro-4,G-O-be11zylidene-a-n-allopyratoide and methyl 2,3-anhydro-4,6-0-benzylidene-a-~-1nan11opyra11oside respectively.These two thio ethers were successfully reduced by sodium in l i q~~i d ammonia to methyl ~-deoxy-2-t11ercapto-or-~-altropyranoside and methyl 3-deosy-3-tnercapto-or-D-altropyranoside. A n attempted replacement of the tosyl group in 1,2;5,U-cli-0-isopropylidene-:M-tosyl-or-~-glucofuranose by benzyl mercaptan was uns~~ccessful. INTRODUCTIOSThe preparation of non no saccharides in which an oxygen atom has been replaced by a sulphur atom has received renewed attention in recent years, primarily due to the fact that these co~npounds provide a route to the synthesis of deoxy sugars. A review by Raymond covering the literature on thio sugars to 1944 (1) refers t o the preparation of a number of thioglycosides and w-deoxy-w-alkylthio-hexoses and -pentoses. The only monosaccharide mentioned which contained a free mercapto group on a carbon atoll1 other than the anomeric carbon ( 2 4 ) was a substance clescribed as "3-deoxy-3-mercapto-D-glucose" obtained by Freudenberg and Wolf (5) in their attempt t o apply the Tschiigaeff reaction (6) to the preparation of an unsaturated monosaccharide.Since 1944, a considerable amount of work has appeared in this area, but primarily concerning the preparation of the thioglycosides and thio ethers of monosaccharides (7-12). A few reports have been ~n a d e of the preparation of monosaccharides with a free nlercapto group. An improved synthesis of 1-thio-D-glucose by the reaction of hydrogen sulphide with l,2-anhydro-D-glucose and its 3,3,G-tri-0-acetate in dimethylformamide has been clescribed (13). The reduction with lithium aluminum hydride of 5,G-dideoxyd,G-epithio-l,2-O-isopropylicle1~e-~-~-iclose has yielded 5,0-dideoxy-5-mercapto-L-idose (14). There has also been reported the preparation of 5,G-clideoxy-1,2-0-isopropylidene-5,G-(t11iocnrbonyldithio)-p-L-idose, a compound wi~ich, no doubt, can be reduced readily to 5,G-dideoxy-1,2-O-isopropylidene-5,G-climercapto-~-~-idose with lithium alumini~m hydride in accordance with similar reductions carried out on the trithiocarbonates of seine hexitols (14,15).Since a number of mercapto monosaccharicles were required in this laboratory, a program for their preparation was begun. This paper presents some results obtained in this direction. RESULTS .ASI> DISCGSSIOSThe debenzylation of S-benzylcysteine has been accomplished by the use of sodiunl in liquid ammonia (lG) and this technique has been successfully applied in this laboratory to the preparation of ~nercaptoindoles (17). These results suggested that mercapto monosaccharides might be prepared by the reaction of beilzyl mercaptan with suitable anhydro monosaccl~arides followed by the reductive cleavage of the resulting benzylthio ethers with sodium in...

REDUCTIVE CLEAVAGE WITH METAL IN LIQUID AMMONIA: I. THE SELECTIVE CLEAVAGE OF THE BENZYLTHIO C—S BOND VERSUS THE BENZYLIDENEDIOXY C—O BOND IN METHYL S-BENZYL-4,6-O-BENZYLIDENE-2-THIO-α-D-ALTROPYRANOSIDES; THE INFLUENCE OF THE COSOLVENT 1,2-DIMETHOXYETHANE ON THE COURSE OF THE REACTION

“…Groups such as benzyl, benzyloxycarbonyl, and p-toluenesulfonyl, which are used to protect amino, hydroxy, or mercapto functions, are readily reilloved by the reducing action of sodium and liquid an~monia. Several articles have appeared (3)(4)(5)(6) which illustrate the use of this technique in the synthesis of carbohydrate derivatives.…”

Versuche zur Synthese der 4‐Thio‐D‐glucose

“…5, leicht erhdtlichen krist. Tosylat 14 der 1,6;3,4-Dianhydro-p-D-galaktopyranose (13) [4] uber die 1,6 ; 2,3-Dianhydro-4-S-benzyl-4-thio-p-D-mannopyranose (22) unter hydrolytischer Offnung des 2,3-Epoxid-Rings zum 4-S-Benzyl-4-thio-lavoglucosan (30) und weiter durch reduktive Debenzylierung und Hydrolyse des 1,6-Anhydrorings zur 4-Thio-~-glucose (31) zu gelangen.…”