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Synthesis and characterization of mibolerone

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Abstract

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.

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China

    Yang Qing  (杨 青), Fan Bo-lin  (范柏林) & Tang Rui-ren PhD  (唐瑞仁) (Professor)

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  1. Yang Qing  (杨 青)
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  2. Fan Bo-lin  (范柏林)
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  3. Tang Rui-ren PhD  (唐瑞仁)
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Correspondence to Tang Rui-ren PhD  (唐瑞仁).

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Foundation item: Project(50573019) support by the National Natural Science Foundation of China

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Yang, Q., Fan, Bl. & Tang, Rr. Synthesis and characterization of mibolerone. J Cent. South Univ. Technol. 14, 524–527 (2007). https://doi.org/10.1007/s11771-007-0102-4

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  • DOI: https://doi.org/10.1007/s11771-007-0102-4

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