856. Totally synthetic steroid hormones. Part II. 13β-Alkylgona-1,3,5(10)-trienes, 13β-alkygon-4-en-3-ones, and related compounds

Abstract

By using procedures previously developed for (*)-cestrone,l a variety of ( &)-13p-alkylgona-l,3,5( 10)-trienes and cognate compounds has been synthesised and converted into various ( & ) -1 3p-alkylgon-4-enes. Biological activities are given for several compounds and in some cases compared with those of the corresponding (+)and (-)-enantiomers.A series of related (&)-cestranes has been totally synthesised for comparison in biological activities with these gonanes and the corresponding cestranes prepared from (+)-oestrone. Preliminary accounts of some of this work have been given. R1 = Et, R2 = Me, R3 = H, n = 2), made by a sequence involving interaction of the ketone (8; R1 = Et, R2 = Me, n = 2) with methylmagnesium bromide. This alcohol may be a 17ap-01 from its appreciable androgenic-anabolic activity (below) and the reported 22 lack of such activity in 17a-hydroxy-19-norandrost4en-3-one, but the evidence is inconclusive. Ananchenko et aZ.l% observed the formation of both possible epimers in a similar Grignard reaction with the cestratetraene (8; R1 = R2 = Me, n = 2).

Hemilabile Benzyl Ether Enables γ-C(sp3)–H Carbonylation and Olefination of Alcohols

“…Finally, we demonstrated the potential utility of both the carbonylation and olefination with a late-stage modification of the estrogen steroid hormone, β-estradiol (Scheme ). Substitution at the C13 position was believed to be important for high bioactivity, and a great number of derivatives with variations on the C13 position have been prepared by both pharmaceutical companies and academic laboratories. , We envisioned that these compounds could be synthesized more efficiently by using the new strategy. 1x can be easily prepared from commercially available β-estradiol by methylation of the phenol moiety and subsequent auxiliary installation.…”

“…In contrast, the corresponding racemate required a six-step synthesis previously . Likewise, subjecting 1x to the ethylene insertion conditions and subsequent debenzylation afforded 5x′ , which previously required a 17-step synthesis …”

Synthesis of Novel Structurally Simplified Estrogen Analogues

“…Heating of 13 with the alkylated 1,3-cycloalkanediones 11 a-c and 12 a-c, which were either commercially available or synthesized by known literature procedures, [17] in CH 3 CN in the presence of NEt 3 at reflux gave the desired compounds 7 a-c and 8 a-c in very good yields (Scheme 3).…”

Entwicklung auf dem Gebiet der Gestagene

“…Ein weiterer groûer Schritt in der Entwicklung von Gestagenen gelang in den 70 er Jahren in den USA mit dem Norgestrel (Smith et al, 1964), wobei die Methylgruppe am C-Atom 18 durch eine ¾thylgruppe ersetzt wurde. Norgestrel und seine später synthetisierte biologisch aktive Form (Norgestrel ist ein Racemat), das Levonorgestrel (Rufer et al 1967), waren nicht nur erheblich wirksamer als Norethisteron, sondern sie unterschieden sich auch positiv im Wirkungsspektrum vom Norethisteron.…”