RESUMO
The palhinine family of Lycopodium alkaloids were first reported in 2010, which feature an intriguing isotwistane carbon cage and a nine-membered azonane ring. It is noteworthy that the tetracyclic 5/6/6/9 skeleton was unprecedented in Lycopodium alkaloids before their seminal discovery. Over the past decade, extensive synthetic efforts stemming from seven research groups have resulted in two racemic total syntheses to date. This review article takes the opportunity to survey these efforts and achievements so as to promote further research towards the asymmetric total synthesis of palhinine alkaloids.
Assuntos
Alcaloides/síntese química , Carbono/química , Lycopodium/química , Produtos Biológicos/farmacologia , Química Farmacêutica/métodos , Química Farmacêutica/tendências , Ciclização , Desenho de Fármacos , Estrutura Molecular , EstereoisomerismoRESUMO
Five cholic acid derivatives (including allo-ω-muricholic acid and CDCA) were synthesized from hyodeoxycholic acid via selective oxidation of C3- or C6-hydroxyl groups by IBX and NBS oxidants and stereocontrolled conversion. The hydroxyl group could be introduced through hydrolyzing α-Br keto with K2CO3 aqueous solution or through oxidizing the double bond by monoperoxyphthalic acid. The reduction of C6-O6 carbonyl to methylene could undergo with PTSH, NaBH3CN and ZnCl2 only at 5ß configuration. A feasible synthetic route of CDCA from HDCA has been established to avoid the epimerization with the yield of 45% (8 steps). These strategies provided good yields, stereoselectivity and reproducibility for the preparation of cholic acid derivates and CDCA.
Assuntos
Ácido Cólico/síntese química , Ácido Desoxicólico/química , Ácido Cólico/química , Conformação Molecular , EstereoisomerismoRESUMO
A concise synthesis of the tricyclo[4.3.1.03,7]decane caged core of palhinine alkaloids was developed with SmI2-mediated cyclization and light-initiated radical addition-fragmentation as key steps. Compared with the reported racemic routes which are all based on Diels-Alder-type key reactions, our strategy would be more readily accessible to the asymmetric total syntheses of the palhinine alkaloids.