Federico G. De las Heras

Synthesis of ribosyl and arabinosyl cyanides by reaction of 1-O-acyl sugars with trimethylsilyl cyanide

A new procedure is described for the synthesis of glycosyl cyanides by reaction of 1-O-acyl sugars with trimethyl-silyl cyanide in a polar aprotic solvent and in the presence of a Lewis acid as catalyst. A variety of ribosyl and arabinosyl cyanides have been made in this way from sugar derivatives having acyl, chloro, or methoxy leaving groups at the anomeric position, furanose or pyranose rings, and acyl or benzyl protecting groups. The 1,2-Trans-glycosyl cyanide was formed when the starting sugar had a participating 2-O-acyl substituent. A mixture of cyanide anomers was obtained when the starting sugar was protected with non-participating benzyl groups.

Cyanosugars—II: Synthesis of hexopyranosyl cyanides by reaction of glycals with trimethylsilyl cyanide

Abstract 3,4,6-Tri-O-acetyl-O-glucal and 2,3,4,6-tetra-O-acetyl-2-hydroxy-D-glucal reacted with Me3SiCN in the presence of a Lewis acid (SnCl4, BF3) as catalyst to give anomeric pairs of 2,3-dideoxy-hex-2-enopyranosyl cyanides and 3-deoxy-hex-2-enopyranosyl cyanides. These 2,3-unsaturated glycopyranosyl cyanides were hydrogenated over Pd C to afford the corresponding 2,3-dideoxy- and 3-deoxy-hexopyranosyl cyanides.

3'-C-cyano-3'-deoxythymidine

3′-C-Cyano-3′-deoxythimidine (2) has been synthesized in 8 steps from 1-(β-D-ribofuranosyl)-thymine (3). 3 Was transformed to the corresponding 3′-ketonucleoside 5, which by addition of HCN followed by deoxygenation of the 2′-OH and 3′-OH groups of the resulting cyanohydrin gave 2.

Cyanosugars. IV. Synthesis of α-D-Glucopyranosyl and α-D-Galactopyranosyl Cyanides and Related 1,2-CIS C-Glycosides

Abstract Reaction of 1-O-acetyl-2,3,4,6-tetra-O-benzyl-D-glucopyranose (1) and the corresponding galactopyranose (2) with trirnethylsilylcyanide in the presence of BF3 afforded a mixture of the β- and α-D-glucopyranosyl cyanides, 3 and 5, and the β— and α-D-galactopyranosyl cyanides, 4 and 6, respectively, in good yields. Reduction of the cyano groups of 3 and 5 with 1 mol of LiAlH4 gave the 1-amino-1-deoxy-D-glycero-D-gulo- and D-glycero-D-ido heptitols, 8 and 10, respectively. Reduction of 5 with 0.5 mol of LiAlH4 afforded, after work up, the corresponding D-glycero-D-ido-heptopyranose (11).

Stereospecific synthesis of branched-chain sugars by a novel aldol-type cyclocondensation

Abstract A procedure for the preparation of branched-chain sugars having highly functionalised C -branches is reported. Reaction of furanos-3-uloses, pyranos-3-uloses, or pyranos-2-uloses with sodium cyanide followed by mesylation of the corresponding cyanohydrin afforded α-mesyloxynitriles which, on treatment with base, underwent aldol-type cyclocondensation to yield furanose-3-spiro-, pyranose-3-spiro-, and pyranose-2-spiro-5′-(4′-amino-1′,2′-oxathiole-2′,2′-dioxide) derivatives. Treatment of the furanose-3-spiro derivatives with methanolic sodium methoxide gave C -[( E )-1-amino-2-(methoxysulfonyl)vinyl] branched-chain sugars having the same configuration as the starting cyanohydrins.

Novel aldol-type cyclocondensation of O-mesyl (methylsulphonyl) cyanohydrins. Application to the stereospecific synthesis of branched-chain sugars

Reaction of O-mesylcyanohydrins of furanos-3-uloses with base afforded furanose-3-spiro-5′-[4′-amino-1′,2′-oxathiole-2′,2′-dioxide] derivatives, which on treatment with MeONa/MeOH gave C-[(E)-2-(methoxysulphonyl)-1-(amino)-vinyl] branched-chain sugars, having the same configuration as the starting cyanohydrins.

New routes for the synthesis of pyrrolo-[3,2-d]- and -[2,3-d]-pyrimidine systems starting from a common pyrrole derivative

New routes for the synthesis of pyrrolo-[3,2-d]- and -[2,3-d]-pyrimidines from a common 2,3-dicarboxypyrrole derivative are described. The common starting material, 3-ethoxycarbonyl-2-carboxy-4-methylpyrrole (1) is conveniently functionalized to give 2- or 3-azidocarbonylpyrroles (4), (17), and (22) which on Curtius rearrangement followed by treatment with ammonia or amines give the pyrrolylurea (6a) or its derivatives (6b–d), or (23). These, in basic medium cyclise to 7-methylpyrrolo[3,2-d]pyrimidine-2,4-diones (7a), its 3-substituted derivatives (7b–d), or to 5-methylpyrrolo[2,3-d]pyrimidine-2,4-diones (19).

Aldol reaction of nucleoside 5'-carboxaldehydes with acetone. Synthesis of 5'-C-chain extended thymidine derivatives

Abstract Reaction of 3′-0-(t-butyldimethylsilyl)-2′-deoxythymidine-5′-carboxaldehyde and 2′,3′-dideoxythymidine-5′-carboxaldehyde with acetone afforded a 3:2 mixture of the two (5′R)- and (5′S)-5′-acetonylthymidine derivatives.

Synthesis of 3′-C-ethynylnucleosides of thymine

Abstract Reaction of 1-[2,5-di- O -(t-butyldimethylsilyl)-β- D - erythro -pentofuranos-3-ulosyl]thymine with HCCMgBr gives a (25:1) mixture of 3′- C -ethynyl nucleosides of thymine having β- D - xylo and β- D - ribo configuration. Reaction of 1-(2′-deoxy-5′- O -trityl-β- D -glycero-pentofuran-3-ulosyl)thymine with HCCMgBr gives the corresponding 3′- C -ethynyl-β- D - threo -thymidine. The absolute configurations of the newly formed chiral centers at C-3′ have been demonstrated by chemical means.

Hexose-modified anti-viral analogues of uridine 5′-disphosphate glucose derivatives

Abstract A series of analogues of the anti-viral 5′- O -[[[[(tetrabenzyl-, or tetrabenzoyl-α- d -glucopyranosyl)oxy]-carbonyl]amino]sulfonyl]uridine, in which the α-glucose moiety has been replaced by α-mannose, or galactose, 2-acetamido-2-deoxy-α-glucopyranose, 2-deoxy-α-, and β-glucopyranose, 6-deoxy-α-, and β-glucopyranose and 2,4-dideoxy-α-glucopyranose, has been synthesized by reaction of the corresponding protected hexose having the 1-OH free with chlorosulfonyl isocyanate and 2′,3′- O -isopropylideneuridine. 5′- O -[[[[(2″,3″,4″,6″-Tetra- O -benzoyl-α- d -mannopyranosyl)oxy]carbonyl]- amino]sulfonyl]-2′,3′- O -isopropylideneuridine( 13 ), 5′- O -[[[[(2″,3″,4″,6″-tetra- O -benzoyl- and 2″,3″,4″,6″-tetra- O -benzyl-α- d -galactopyranosyl)oxy]carbonyl]amino]sulfonyl]-2′,3′- O -isopropylideneuridine ( 18 and 19 ), 5′- O -[[[[(2″-acetamido-2″-deoxy-3″,4″,6″-tri- O -benzoyl- and 3″,4″,6″-tri- O -benzoyl-2″-deoxy-α- d -glucopyranosyl)oxy]carbonyl]amino]sulfonyl]-2′,-3′- O -isopropylideneuridine ( 20 and 21 ) and the deisopropylidenated derivatives of 13 and 21 , showed anti-viral activity similar to that of the corresponding glucose analogues as determined by the inhibition of the cytopathic effect induced by HSV-1 replication.