An alternative synthesis of 17β‐hydroxy‐7α‐methyl‐19‐nor‐17α‐pregn‐5(10)‐en‐20‐yn‐3‐one (Org OD 14)

Abstract

Abstract. The title compound (4) was prepared starting from 17P,19-dihydroxyandrosta-4,6-dien-3--one 17,Ig-diacetate (5). Copper-catalyzed conjugate addition of methylmagnesium iodide gave, after hydrolysis, 17P, 19-dihydroxy-7a-methylandrost-4-en-3-one @a), which was converted by oxidation and deacylation into 7a-methylestr-5( lO)-ene-3,17-dione (1 1). Selective protection of the 3-keto group as the dimethyl acetal, followed by ethynylation and deacetalization, gave the desired product 4. The 7P-methyl adduct, a by-product in the Grignard reaction, was removed after the oxidation step. Its structure was confirmed by an independent synthesis of the 7P-methyl-19-aldehyde 9b.

Steroids: reactions and partial syntheses

“…A further synthesis of the 1701-pregn-20-yne (170) involves copper-catalysed conjugate addition of methylmagnesium iodide to the androstadienone (171) to give mainly the 7amethyl adduct, which is converted into the oestrenedione (172) prior to ethynylation. 146 19-Noraldosterone has been prepared by an extension of a recent synthesis of 19-hydroxyaldosterone. 14' The 19-alcohol is oxidized with pyridinium chlorochromate to the 19-0x0compound, which is decarbonylated by heating it with alkali.…”

Novel Stereoselective Synthesis of 7β-Methyl-Substituted 5-Androstene Derivatives

“…Previous reports on the introduction of a 7β-methyl mainly concerned the copper-mediated 1,6-conjugate addition of organometallic reagents to various steroidal 4,6-dien-3-ones. , Because of the special position of C-7, which features little proximal steric difference between the α-side and β-side, both 7α-and 7β-methyl isomers were obtained. Zeelen et al reported that 7β-methyl derivatives of steroids could be stereoselectively synthesized using 19-hydroxyandrost-4-ene-3,17-dione 19-acetate as starting material, but the yield was very low (6.0% overall yield in four steps).

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