Synthesis of a new anti-inflammatory steroidal acid ester: methyl 11 beta-hydroxy-3,20-dioxo-1,4-pregnadien-21-oate.
The synthesis and anti-inflammatory activity of a new steroidal acid ester, methyl 11 beta-hydroxy-3,20-1,4-pregnadien-21-oate (5), are described. This compound has been prepared via three different synthetic routes. The first involves oxidation of the benzoate 3 to the aldehyde 4 followed by a Mattox-type rearrangement of the side chain in conjunction with elimination of the benzoyloxy group. The second method, prolonged reaction of 1-dehydrocorticosterone (8) with methanolic cupric acetate, affords methyl ester 5 in low yield. The third approach consists of selective oxidation at C-20 of the methyl 11 beta, 20 alpha and 20 beta-dihydroxy-3-oxo-1,4-pregnadien-21-oates (7a and 7b) with sulfur trioxide-pyridine complex. The local anti-inflammatory activities of the new ester 5 and intermediates 3, 4, 7a and 7b were determined by the cotton-pellet granuloma assay in rats. The anti-inflammatory activity of the title compound is equal to that of the parent steroid, prednisolone. However, unlike the latter compound, the ester does not cause reduction of adrenal and thymus weights or a lowering of plasma corticosterone levels.
D000287:Administration, Topical; D000311:Adrenal Glands / Q000502:physiology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D003345:Corticosterone / Q000097:blood; D006099:Granuloma / Q000517:prevention & control; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000502:physiology
D000893:Anti-Inflammatory Agents; C045173:methyl 11-hydroxy-3,20-dioxo-1,4-pregnadien-21-oate; D011239:Prednisolone; D003345:Corticosterone