An approach to the stereospecific total synthesis of 5,6-dideoxy-5-amino-hexonic acids and related compounds.

Abstract

An approach to the stereospecific synthesis of polyhydroxy-5-aminohexanoic acids was designed. It was found that 1-chloro-1-nitrosocyclohexane undergoes a Diels-Alder reaction with of methyl sorbate to give one stereoisomer of 3-methyl 3,6-dihydro-1,2-oxazine-6-carboxylic acid methyl ester. A number of derivatives of this latter compound are described. Catalytic hydrogenation afforded one isomer only of 2-hydroxy-5-aminohexanoic acid, a novel amino acid, Hydroxylation of the Diels-Alder adduct (as the N-benzoyl derivative) with osmium tetroxide followed and by hydrolysis and hydrogenation afforded what is tentatively regarded as 5,6-dideoxy-5-aminotalonic acid. Epoxidation of the adduct peroxytrifluoroacetic acid gave a 50:50 mixture of crystalline epoxides which were separated. The configuration of these epoxides was deduced from a study of their reaction with hydriodic acid. Pure stereoisomeric iodohydrins were obtained which were assigned configurations on the basis of their behavior under conditions of methanolysis. Similarly, chlorohydrins were obtained and assigned configurations by analogy with the course of iodohydrin formation. Reaction of the oxides with formic acid followed by methanolysis afforded a single mixture of trans-diols (3,4,5,6-tetrahydro-3-methyl-4,5-dihydroxy-1,2-oxazine-6-carboxylic acid methyl ester), which are useful potential precursors of additional aminosugar-like compounds. Spectroscopic (IR and NMR) properties of several of the compounds are reported. Mechanistic considerations lead to the conclusion that the formation of the starting adduct probably proceeds by way of a two-step process, a course of reaction which is without precedent.