Synthesis of a new anti-inflammatory steroidal acid ester: methyl 11β-hydroxy-3,20-dioxo-1,4-pregnadien-21-oate

Article abstract of DOI:10.1002/jps.2600740215

The synthesis and anti-inflammatory activity of a new steroidal acid ester, methyl 11β-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-dehydrocortisone (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 11β,20α and 20β-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.