Microbial oxidation of aromatics in enantiocontrolled synthesis. Part 1. Expedient and general asymmetric synthesis of inositols and carbohydrates via an unusual oxidation of a polarized diene with potassium permanganate

Abstract

This paper reports on the details of a general design of carbohydrates and cyclitols from biocatalytically derived synthons. Homochiral 1-halogenocyclohexa-4,6-diene-2,3-diols 1a and 1b have been generated from chloro- and bromo-benzene, respectively, by means of bacterial dioxygenase of Pseudomonas putida 39D. These chiral synthons have been manipulated to cyclitols and carbohydrates by further stereoselective functionalizations. The preparation of D-chiro-inositol, neo-inositol, muco-inositol, and allo-inositol exemplifies their use in enantiocontrolled synthesis. A novel oxidation of polarized dienes with KMnO₄ resulted in the synthesis of α-halogeno epoxy diols, which proved unexpectedly stable. A mechanism is proposed for this transformation and placed in context with the only four reported examples of this reaction in the literature. In addition to the application of this new chemistry to the synthesis of cyclitols, chloro epoxy diol 21a has been transformed into a series of cyclitol synthons by reductive or hydrolytic operations. Reaction of 21a with ammonia led to the preparation of highly oxygenated pyrazines, whose structures were proven by X-ray crystallography. The use of 21a in the preparation of D-chiro-3-inosose, a hitherto unreported cyclitol derivative, is also reported. In addition, chloro epoxy diol 21a was transformed into D-erythruronolactone, completing the synthesis of this important chiral pool reagent in two operations from chlorobenzene. Oxidative cleavage of tetrol 20 yielded D-mannosolactone identical with an authentic sample.