Leon Goodman

Neighboring-Group Participation in Sugars

Publisher Summary This chapter discusses a substantial proportion of the antibiotics that contain carbohydrate moieties, which covers a wide range of structures. Many of the syntheses involve changes as the conversion of a trans-1,2-glycol into a cis-1 ,2-glycol, a trans-1-2-amino alcohol into a cis-1, 2-amino alcohol, or replacement of a hydroxyl group by some other functional group; in classical aliphatic or alicyclic chemistry, these changes are accomplished by conventional, nucleophilic-displacement reactions of the S N 2 type2 on a sulfonic ester of a hydroxyl group. The secondary sulfonates on sugar rings are, however, very unreactive toward S N 2 displacements; when most of this synthetic work on rare sugars is initiated, the only useful reaction of this type that had been reported of 1, 2: 5, 6-di-O-isopropylidene-3-O-p-tolylsulfonyl-α-D-glucofuranose. This chapter considers all of the intramolecular displacements in sugars, except for the three general classes of reaction.

Synthetic C-nucleosides: 3-(α- and β-D-arabinofuranosyl)pyrazolo[4,3-d]pyrimidine-5,7-diones

Abstract 2,3,5-Tri- O -benzyl- D -arabinofuranosyl bromide ( 4 ) was converted into 2,5-anhydro-3,4,6-tri- O -benzyl- D -glucononitrile ( 5 ), mixed with 20% of the D - manno epimer 6 . The mixture was reduced to the amine 7 , which via the N -nitrosoacetamide 10 afforded the 1-deoxy-l-diazo sugar 11 . Dipolar addition to dimethyl acetylene-dicarboxylate afforded the C -nucleoside derivative, dimethyl 3-(2,3,5-tri- O -benzyl-α-β- D -arabinofuranosyl)pyrazole-4,5-dicarboxylate ( 20 ). Selective ammonolysis afforded the 4-ester-5-carboxamide 21 , which was separated chromatographically into the α-(minor) and β-(major) anomers. Hydrazinolysis and Curtius reaction of the pair of 4-acid hydrazides (α- 22 and β- 22 ) afforded the anomeric 3-glycosyl-1 H -pyrazolo-[4,3- d ]pyrimidine-5,7-diones (α- 24 and β- 24 ). Hydrogenolytic debenzylation yielded the β- D )- arabino epimer ( 1 ) of oxoformycin B , and the α- D - arabino form 2 . These anomeric C -nucleosides were distinguished by circular dichroism spectra that showed the same relationship as α- and β- D - arabino anomers of normal purine nucleosides.

Some 2-fluoroethylamines derived from hydrocinnamic acid, phenylpyruvic acid and DL-phenylalanine☆

Abstract Fluorine-containing nitrogen mustards attached to hydrocinnamic acid, phenylpyruvic acid and D,L -phenylalanine as carrier groups have been synthesized. The N-(2-chloroethyl)-N-(2′-fluoroethyl)amines are obtained by alkylation of the sodium salts of N-(benzyloxycarbonyl)amines with 2-fluoroethyl p-toluenesulfonate or 2-bromofluorethane, removal of the benzyloxycarbonyl group, followed by hydroxyethylation and chlorination. The bis(2-fluoroethyl)amines are obtained by heating the bis(2-p-toluenesulfonyloxyethyl)amines with potassium fluoride in a suitable solvent. By these reactions, methyl m-aminohydrocinnamate was converted to the chlorofluoro mustard XIX and the bis-fluoro mustard XX. Starting with aniline, the above reactions, in conjunction with the Vilsmeier-Haack reaction, afforded the benzaldehyde mustards VII and VIII. These are converted to the corresponding azlactones. A two-step hydrolysis of the azlactones afforded the chlorofluoro mustard IXA and the bisfluoro mustard IXB of phenylpyruvic acid. Reduction of the azlactone with zinc and acid, followed by hydrolysis, afforded the corresponding D,L -phenylalanine mustards XIIIA and XIIIB.

Synthesis of the nucleoside antibiotic formycin B

Curtius rearrangement of the 4-azide of 5-(tri-O-benzyl-β-D-ribofuranosyl)pyrazole-3,4-dicarboxylic acid gave the N-carboxy-anhydride of the 4-amino-3-acid the methyl ester of which, on heating in formamide followed by catalytic hydrogenolysis, gave formycin B.

Synthesis of some 2′-deoxyribosides of 8-azaadenine☆

Abstract The α- and β-anomers of 9-(2′-deoxy- d -ribofuranosyl)-8-azaadenine were synthetized by a chemical method. The β-anomer was compared with the 2′-deoxyribosyl-8-azaadenine obtained by enzyme action, and the two are shown to be identical.

RECENT ASPECTS OF OLEFIN SULFIDE CHEMISTRY

Abstract The three-membered heterocyclic compounds (I) are designated variously as episulfides, thiacyclopropanes, olefin sulfides or thiiranes. A comparison of the episulfides (I) with their oxygen analogs, the epoxides, is almost inevitable in view of their structural similarity and the proximity of sulfur to oxygen in the periodic table; some general statements comparing the two classes of compounds can be made. The episulfides are more prone to spontaneous polymerization than are the corresponding epoxides and are less convenient compounds to store. The desulfurization of episulfides both thermally and with a variety of reagents to give the corresponding olefins is a very common reaction; the similar deoxygenation of epoxides is possible only with a few of those reagents and then under much more vigorous conditions. The direction of ring-opening of episulfides by various reagents has been investigated to a very small extent as compared to the corresponding reactions of epoxides; it appears, however, on the basis of what is known at present, that different rules apply for the two classes of compounds with at least some of the examples that have been studied.

Synthesis of C-nucleoside analogues by 1,3-dipolar addition of a 1-diazo-sugar to acetylenes

The 1-diazo-sugar (VII), prepared by base treatment of 2,5-anhydro-1-deoxy-3,4-O-isopropylidene-1-nitrosoureido-DL-ribitol (VI), underwent 1,3-dipolar addition with dimethyl acetylenedicarboxylate in nearly quantitative yield, forming dimethyl 3-(2,3-O-isopropylidene-β-DL-erythrofuranosyl)pyrazole-4,5-dicarboxylate (VIII) and providing a pathway to C-nucleosides.