Synthesis and characterization of mibolerone
- 90 Downloads
A simple and effective route for the synthesis of mibolerone was described starting from the estr-5(10)-en-3,17-dione in four steps with the overall yield of 47.0%. Thus, two methods for key intermediate methylnorandrost were investigated: one(method A) starting from estr-4-en-3,17-dione underwent 3-keto group protected with ethyl orthoformate to give 3-ethoxy-3,5-dien-estr-17-one, the other(method B) from estr-5(10)-en-3,17-dione and protected 3-keto group to give 3,3-dimethoxy-estr-5(10)-7-one in a mild acidic condition. Then, two intermediates were subsequently reacted with methyllithium followed by a mild hydrolytic procedure and gave methylnorandrost with total yield 25.0% and 86.0%, respectively. In the preparation of 6-dehydrogenation product of methylnorandrost, two procedures(method C and method D) were investigated: one was the protected 17α-methyl-17β-hydroxy Δ3,5-enol ethers estrendiene brominated and the resulting 6-bromo-19-methylnortestosterone was then immediately dehydrohaloenated to give 6-dehydro-19-methylnortestosterone, the total yield only reaches 36.0%; the other was directly dehydrogenated with chloranil and the yield reaches 75.6% under the optimum conditions: in refluxing tetrahydrofuran, the molar ratio of methylnorandrost to chloranil is 0.66 and reaction time of 5 h. The titled compound and intermediates were characterized by 1H and 13C NMR, IRMS and elemental analysis.
Key wordsmibolerone methylnorandrost steroids synthesis hepatic androgen receptor
Unable to display preview. Download preview PDF.
- LOAN L, POIRIER D, PROVENCHER L. New efficient pathway for the synthesis of 3-aminoesterone[J]. Tetrahedron Letters, 2001, 43(15): 7617–7619.Google Scholar
- STOJANOVIC S, GABOR D M, MEDIC-MIJACEVIC L. Synthesis and chemical behaviour of 17-α-butyl-3β, 17β-dihydroxy-16-oximino-5-androstene[J]. Steroids, 2001, 66(1): 23–26.Google Scholar
- HO R Y, NI Y, LOU H Z, et al. Antifertility steroid—Synthesis of 7α-methyl-17β-hydroxy-estr-5-ene-3-one[J]. J Chinese Organic Chemistry, 1981, 19(5): 347–349. (in Chinese)Google Scholar
- FUHRHOP J, PENZLIN G. Organic Synthesis[M]. Weinheim, Germany: VCH Verlagagesllschaft mbH Weinheim, 1994: 277–288.Google Scholar
- FRIED J, EDWARDS J A. Organic Reactions in Steroid Chemistry[M]. New York: Van Nostrand Reinhold Company, 1972: 375–379.Google Scholar