ABSTRACT
Two different synthetic routes have been used to synthesize a series of cyclopropyl conjugated ketones in which 4alpha,6-unsaturation replaces the usual 4,5-unsaturation. The synthetic routes involve intramolecular ketocarbene addition to a 5-6 double bond and intramolecular 1,3-elimination of 6beta-substituted 5beta-3-keto steroids. Both routes give 5beta products. The analogs of progesterone, testoterone acetate, and norethisterone have been prepared and shown to be remarkably biologically inactive when compared with the corresponding standard. Possible reasons for such inactivity are discussed.
Subject(s)
Cyclosteroids/chemical synthesis , Androgens/pharmacology , Animals , Contraceptives, Postcoital, Synthetic/pharmacology , Cyclosteroids/pharmacology , Female , Male , Molecular Conformation , Organ Size/drug effects , Ovulation/drug effects , Pregnancy , Progestins/pharmacology , Prostate/drug effects , Rabbits , Rats , Seminal Vesicles/drug effectsABSTRACT
Whereas wild-type strains of Saccharomyces cerevisiae can synthesize up to 7% dry weight of ergosterol, a polyene-resistant mutant has been obtained which produces no ergosterol. Instead, a C-28 methyl sterol is produced, and it has been identified as Delta(8(9),22)-ergostadiene-3beta-ol. This sterol is converted to ergosterol by wild-type yeasts and is observed transiently in cells during aerobic adaption of anaerobically grown wild-type yeasts. The new sterol is proposed as an intermediate in ergosterol biosynthesis.
