Through The Series Of Acetyl Inverse Aldol Reaction, Aromatization, Etherification Reaction Synthesis Female Phenol - 3 - Alkyl Ether Ketone Type Of Estrogen

Estrone3-alkyl ethers,semi-synthetic estrogen,have beencommercially available as long-acting oral drug or biologically inactiveprodrug.This kind of estrogen drugs in the past is mainly as raw materialby the estrone,and expensive and high toxic alkylation reagents usedwas etherification.And the demand for estrone though Bio-extraction islimited, the total synthesis are more steps,and stereoscopic chemistry isdifficult to control,so them are synthesized by semi-synthetic.The currentdomestic production line of estrone is mainly as the starting material byDiosgenin.In the route of the synthesis of estrone there are kinds ofproplems:route lengthy,inefficient,violent reaction,Strict requirements tothe substrate structures and reaction equipments,heavy metalpollutions,and toxic alkylating reagents used,these in pharmaceuticalindustry is extremely disadvantageous.Through the optimization,weshows that these estrogens are synthesized efficiently in the series ofdeacetylation-retro-Aldol reaction-aromatization-etherificationreaction.Preparation of estrogens3-alkyl ethers with19-hydroxyandrost-4-ene-3，17-dione as starting material seemedparticularly attractive. The advantages of this protocol are (1)thesteroidal resources is commercially available,which is prepared fromabundant steroid resources;(2)non-aromatic starting materials areeasily amendable;(3)A variant of the protocol provided anunprecedented approach to synthesize estrone3-alkyl ethers such asmestranol, quinestrol, and promestriene without using toxic alkylatingreagents.In summary,the efficient1,2-dehydrogenation in combination withsubsequent retro-aldol-type aromatization provides a practicalprotocol for the synthesis of estrogens from easily available 19-hydroxyandrost-4-ene-3,17-dione. Based on the current protocol,pharmaceutically attractive estrogens were efficiently synthesized.