title: Phytosterols as precursors for the synthesis of aromatase inhibitors: Hemisynthesis of testololactone and testolactone.
abstract: Using β-sitosterol and stigmasterol as precursor materials, a concise and efficient hemisynthesis of aromatase inhibitors: testololactone and testolactone was accomplished in a well-established reaction scheme. It involves highly effective Oppaneur oxidation of both β-sitosterol as well as stigmasterol to generate the required enone moiety in ring 'A' of the desired steroid system. The Oppaneur oxidation products of both β-sitosterol and stigmasterol were then subjected to oxidative cleavage of the side chain to produce 4-androstene-3,17-dione. Baeyer-Villiger oxidation of 4-androstene-3,17-dione using m-CPBA yielded testololactone. Dehydrogenation of 4-androstene-3,17-dione using phenylselenyl chloride in ethyl acetate followed by selenoxide elimination with H2O2 in dichloromethane furnished androstenedienone. Baeyer-Villiger oxidation of the resulting androstenedienone yielded the desired testolactone (overall yield 33%). This expeditious reaction scheme may be exploited for the bulk production of aromatase inhibitors (especially testolactone marketed under the brand name Teslac) from the most abundant and naturally occurring phytosterols like β-sitosterol.
authors.affiliation: Bioorganic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Srinagar, 190005 Jammu and Kashmir, India.
authors.forename: Shabir H
authors.initials: SH
authors.lastname: Lone
authors.affiliation: Bioorganic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Srinagar, 190005 Jammu and Kashmir, India. Electronic address: kabhat@iiim.ac.in.
authors.forename: Khursheed A
authors.initials: KA
authors.lastname: Bhat
mesh_terms: D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D010084:Oxidation-Reduction; D010840:Phytosterols; D012855:Sitosterols / Q000737:chemistry*; D013265:Stigmasterol / Q000737:chemistry*; D013738:Testolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D047072:Aromatase Inhibitors; D010840:Phytosterols; D012855:Sitosterols; C018155:testololactone; C025473:gamma-sitosterol; D013738:Testolactone; D013265:Stigmasterol
keywords: Sitosterol; Stigmasterol; Teslac; Testolactone; Testololactone