A kind of preparation method of 3α-hydroxyl-5α, 14β-androst-15-en-17-one

Abstract

The invention belongs to the field of chemical synthesis, and relates to a preparation method of a compound 3α-hydroxyl-5α, 14β-androst-15-en-17-one, which uses natural steroid 3α-hydroxyl-5α, 14α-androst The ster-17-one is reacted with a brominated ketone as a raw material, and then the target product is obtained through the steps of dehydrobromination into olefin and isomerization under the action of an acid-base catalyst. The invention provides a synthetic method of a new compound 3α-hydroxyl-5α,14β-androst-15-en-17-one containing 14βH, and the obtained product has the configuration of 14βH and α ,β‑unsaturated carbonyl structural unit, which plays an important role in biological activity.

Description

technical field [0001] The present invention belongs to the field of chemical synthesis, and relates to a preparation method of a compound. Specifically, a new compound 3α- Synthesis of hydroxy-5α,14β-androst-15-en-17-one. Background technique [0002] The chemical modification of natural steroids has become an important field of new drug research. By modifying the chirality of the parent ring structure of the steroid or the modification of the functional group, some important steroid compounds with better biological activity than the parent can be obtained [Levina, I.S. ; Pokrovskaya, E.V.; ​​Kulikova, L.E.; Kamernitzky, A.V.; Kachala, V.V.; Smirnov, A.N. Steroids. 2008, 73, 815]. Among them, the more important chemical modification of natural steroids is the inversion of 14αH to 14βH configuration. Through configuration reversal, many 14βH steroid compounds have special physiological activities, such as being used in contraceptives [A.Cleve, G.Neef, E.Ottow, S.Scholz, an...

AI Technical Summary

Problems solved by technology

The halogen on the α-carbon of D ring 17-carbonyl can be hydrolyzed into D ring 16-hydroxy-17-carbonyl compound under basic conditions, and then dehydrated under acidic conditions to obtain steroid D ring 15-ene containing 14αH and 14βH A mixture of -17-ketones, but the separation is difficult [A.Abad, C.Agullo, M.Arno, L.R.Domingo, and R.J.Zaragoza J.Org.Chem.,1990,55(8),2369-73.]

Using a mixed system of lithium carbonate and lithium bromide to promote the elimination of hydrogen halide from natural steroidal α-halogenated D ring 17-carbonyl compounds, part of the 14βH steroid D ring 15-en-17-one can be directly obtained, but the yield Relatively low, raw materials cannot be fully utilized [C.Wang, N.P.Rath, D.F.Covey, Tetrahedron, 2007, 63(33), 7977-7984.]

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