Progestational hormones.

Zderic JA
In: Florkin, M. and Stotz, E.H. eds. Comprehensive Biochemistry 10. Amsterdam, 61 sevier, 1963. p. 166-196

This extensive review covers chemical synthetic procedures for all important protestagens known as of 1960, emphasizing those made by Syntex. Progesterone was identified by Butenandt in 1934, and 10 syntheses were developed by 1947. More economical syntheses were developed by Marker in 1940 from diosgenin, and in 1955 from stigmosterol. In 1960 the only assays for progesterone were the Hooker-Forbes bioassay, chromatography, and determination of urinary pregnanediol. Early derivatives with progestational activity were 17alpha-ethinyltestosterone (1938), 19-norprogesterone (1951), and 17-methylprogesterone. The author also enumerated syntheses for derivatives developed since 1950, listing them by carbon positions: C-2 fluoride; C-4 halide; C-6 epoxides, fluorides, and chloride; oxygen functions at C-16, C-11, C-14, C-15, C-16, C-21; C-16 methyl and cyano; C-17 methyl, bromo, and caproate; C-18 hydroxy; C-21 flouro, methyl and ethyl. The 17alpha caproate is highly active orally and subcutaneously. Syntex synthesized 17alpha-ethinyl-19-nortestosterone; Searl the delta 5-10 isomer and 17alpha-ethyl derivative, and an anabolic progestagen. Finally, routes for synthesizing several active 17alpha-acetoxyprogesterone derivatives are described, including the 6-alpha-methyl-, the 6 methyl-delta6-dehydro-, the 9alpha-fluoro-11beta-hydroxy-, and the 6-chloro-delta6-dehydro-17alpha-acetoxyprogesterone.

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