Cortical Steroid Analogs. III. Further Synthetic and Structure Studies on Acyclic Dihydroxyacetones Derived from 2,3-Butanedione. 1,3-Dihydroxy-3-phenyl-2-butanone¹

Abstract

Methods previously employed in the synthesis of l,3-dihydroxy-3-methyl-2-pentanone (III) failed when applied to 1,3dihydroxy-3-phenyl-2-butanone (X). Because of this, a study of other ester intermediates which might be employed in this synthesis, was undertaken. l-(p-Hydroxybenzoates) could not be converted readily to dihydroxyacetones; however, hydrolysis of the l-(p-nitrobenzoate) and l-(p-chlorobenzoate) of X led to the synthesis of the desired l,3-dihydroxy-3-phenyl-

Cortical Steroid Analogs. IV. gem-Dialkylacetylcarbinols, Hydroxy Enol Ethers, and Hydroxy Ketals from the Reaction of Grignard Reagents and Ethyl Pyruvate Ketal1a

“…Several excellent procedures have been developed for the elaboration of the dihydroxyacetone group common to the antiinflammatory corticosteroids.2 In the preparation of open-chain analogs, there is a greater flexibility of approach in handling this synthetic problem, however, as we have previously demonstrated. 3,4 Contemporarily, the synthesis of the related gemdimethyldihydroxyacetone (la) was recorded by a Russian group.5 Now that a convenient method for the preparation of gem-dialkylacetylcarbinols (III) (Scheme I) is at hand, as described in the foregoing companion paper,6 the synthesis of a series of gem-dialkyldihydroxyacetones corresponding to the parent la has become feasible. The strategic advantage of this approach is that gem-dialkyldihydroxyacetones (I) of high carbon content may be constructed by selection of an appropriate Grignard reagent of less than half as many carbon atoms.6 Accordingly, we have conveniently synthesized the 21-carbon analog (Id), which has a carbon content identical with that of the corticosteroids.…”