P16CM
Chemical Name: 11beta,17alpha,21-Trihydroxy-3,20-dioxopregna-1,4-diene-16alpha-carboxylic acid methyl ester; 11beta,17alpha,21-Trihydroxypregna-1,4-diene-3,20-dione-16alpha-carboxylic acid methyl ester; 16alpha-Methoxycarbonylpregna-1,4-diene-3,20-dione-11beta,17alpha,21-triol
CAS No. 111900-93-7
项目整合开发状态: Preclinical
项目研究机构: Florida A&M University (Originator)
合成路线:P16CM is synthesized from prednisolone (I) via the key 16,17-dehydro intermediate (III).The compound (III) is prepared by literature procedures from prednisolone by its conversion to prednisolone 17,21-diacetate (II),followed by a potassium acetate-induced acyloxy elimination reaction.Michael addition to (III) with KCN provides the 21-acetoxy-16alpha-cyano compound,which is deprotected at C-21 and reprotected with a base-stable tetrahydropyranyl (THP) group to provide (IV).A base hydrolysis of (IV),followed by deprotection at C-21 and esterification at the 16-carboxylate,gives (V),the 17-desoxy analogue of P16CM.17alpha-Hydroxylation of (V) via the intermediate 17,20-enol acetate,using dilute peroxyacetic acid solution at low temperature,yields P16CM.
📌 参考资料/链接：
参考文献标题:Anti-inflammatory carboxy pregnane derivatives
文献作者:Lee,H.J.(Florida Agricultural and Mechanical Univ.)
参考来源:US 4762919; WO 8705028
📄 详细内容
合成路线:P16CM is synthesized from prednisolone (I) via the key 16,17-dehydro intermediate (III).The compound (III) is prepared by literature procedures from prednisolone by its conversion to prednisolone 17,21-diacetate (II),followed by a potassium acetate-induced acyloxy elimination reaction.Michael addition to (III) with KCN provides the 21-acetoxy-16alpha-cyano compound,which is deprotected at C-21 and reprotected with a base-stable tetrahydropyranyl (THP) group to provide (IV).A base hydrolysis of (IV),followed by deprotection at C-21 and esterification at the 16-carboxylate,gives (V),the 17-desoxy analogue of P16CM.17alpha-Hydroxylation of (V) via the intermediate 17,20-enol acetate,using dilute peroxyacetic acid solution at low temperature,yields P16CM.
参考文献标题:P16CM
文献作者:Lee,H.-J.; Taraporewala,I.B.
参考来源:Drugs Fut 1989,14(10),960
合成路线:P16CM is synthesized from prednisolone (I) via the key 16,17-dehydro intermediate (III).The compound (III) is prepared by literature procedures from prednisolone by its conversion to prednisolone 17,21-diacetate (II),followed by a potassium acetate-induced acyloxy elimination reaction.Michael addition to (III) with KCN provides the 21-acetoxy-16alpha-cyano compound,which is deprotected at C-21 and reprotected with a base-stable tetrahydropyranyl (THP) group to provide (IV).A base hydrolysis of (IV),followed by deprotection at C-21 and esterification at the 16-carboxylate,gives (V),the 17-desoxy analogue of P16CM.17alpha-Hydroxylation of (V) via the intermediate 17,20-enol acetate,using dilute peroxyacetic acid solution at low temperature,yields P16CM.
参考文献标题:A novel class of local antiinflammatory steroids.1st communication: Analogues of methyl 11beta,17alpha,21-trihydroxy-3,20-dioxopregna-1,4-diene-16alpha -carboxylate
文献作者:Teraporewala,I.B.; Kim,H.P.; Heiman,A.S.; Lee,H.J.
参考来源:Arzneim-Forsch Drug Res 1989,39821
合成路线:P16CM is synthesized from prednisolone (I) via the key 16,17-dehydro intermediate (III).The compound (III) is prepared by literature procedures from prednisolone by its conversion to prednisolone 17,21-diacetate (II),followed by a potassium acetate-induced acyloxy elimination reaction.Michael addition to (III) with KCN provides the 21-acetoxy-16alpha-cyano compound,which is deprotected at C-21 and reprotected with a base-stable tetrahydropyranyl (THP) group to provide (IV).A base hydrolysis of (IV),followed by deprotection at C-21 and esterification at the 16-carboxylate,gives (V),the 17-desoxy analogue of P16CM.17alpha-Hydroxylation of (V) via the intermediate 17,20-enol acetate,using dilute peroxyacetic acid solution at low temperature,yields P16CM.
参考文献标题:
文献作者:Salce,L.; Hazen,G.C.; Schoenwaldt,E.F.
参考来源:J Org Chem 1970,351681