Elliot L. Shapiro

17-Esters and 17, 21-diesters of 9α, 11β-dichlorocorticoids. Synthesis and anti-inflammatory activity

Abstract The syntheses of some 17,21-diesters of dichlorisone (9α, 11β-dichloro-17α, 21-dihydroxy-1,4-pregnadiene-3, 20-dione), 16α-methyldichlorisone and 16β-methyldichlorisone and some 17-monoesters of 16α-methyldichlorisone are reported. Anti-inflammatory activity, as measured by a granuloma pouch technique, reached a maximum for the 17-butyrate and 17-valerate of 16α-methyldichlorisone and for the 17, 21-dipropionate and 17, 21-dibutyrate of 16α-methyldichlorisone.

Recent advances in the structure-activity relationships of substituted corticosteroids

Abstract The influence of the 6-azido-6-ene grouping on corticosteroid activity has been studied. The 6-azido-6-ene-corticosteroids were synthesized by reaction of the methanesulfonate esters of 6β,7β-dihydroxycorti-costeroids with azide ion. These diols were the unexpected products of the reaction between OsO 4 and 6-ene-corticosteroids. Their β-stereochemistry was assigned unambiguously from their n.m.r. spectra and is contrary to that of some published assignments. Anti-inflammatory activity was measured by the suppression of exudate in the rat granuloma pouch assay. Potency of 9α-unsubstituted corticosteroids was found to be increased by 5–8 times on introduction of the 6-azido-6-ene group. Introduction of this modification into 9α-fluorocorticosteroids enhanced potency in the absence of a 1,2-double bond and left the potency substantially unchanged in the presence of a 1,2-double bond.

Stereoselective β-face catalytic hydrogenation of Δ4-9α-fluoro-11β-hydroxycorticosteroids: reappraisal

At variance with previous reports, palladium-catalysed reduction of 9α-fluorohydrocortisone 21-acetate (1a) and 1,2-didehydro-9α-fluoro-16α-methylhydrocortisone 21-acetate (2a) yields the 5β-configuration.

Effcient synthesis and mechanisms of formation of 4-azido-, 4-thiocyanato-, and 4-isothiocyanato-3-oxo-Δ4,6–steroids

Processes for the preparation of 4-azido-,4-thiocyanato-, and 4-isothiocyanato-3-oxo-Δ4,6–steroids are presented; possible mechanisms of formation are suggested.

RECENT ADVANCES IN THE STRUCTURE–ACTIVITY RELATIONSHIPS OF SUBSTITUTED CORTICOSTEROIDS

The influence of the 6-azido-6-ene grouping on corticosteroid activity has been studied. The 6-azido-6-ene-corticosteroids were synthesized by reaction of the methanesulfonate esters of 6β,7β-dihydroxycorti-costeroids with azide ion. These diols were the unexpected products of the reaction between OsO4 and 6-ene-corticosteroids. Their β-stereochemistry was assigned unambiguously from their n.m.r. spectra and is contrary to that of some published assignments. Anti-inflammatory activity was measured by the suppression of exudate in the rat granuloma pouch assay. Potency of 9α-unsubstituted corticosteroids was found to be increased by 5–8 times on introduction of the 6-azido-6-ene group. Introduction of this modification into 9α-fluorocorticosteroids enhanced potency in the absence of a 1,2-double bond and left the potency substantially unchanged in the presence of a 1,2-double bond.