A second generation formal synthesis of (-)-cephalotaxine.
A second generation formal synthesis of the alkaloid (-)-cephalotaxine has been achieved using an alkylidene carbene 1,5-CH insertion reaction to establish a key quaternary stereocenter. The carbene precursor was readily derived from L-proline, and the 1,5-CH insertion reaction was performed under Ohira's conditions using lithiotrimethylsilyldiazomethane (LTDM), which gave the desired spirocyclic product in 74% yield. The hydroxymethyl group was then oxidized and then decarbonylated (93%), and this material was easily transformed into the desired Friedel-Crafts cyclization precursor. Exposure of this material to SnCl4 then gave the desired pentacyclic product, which was identical to that previously prepared by Mori and thus represents a formal total synthesis of (-)-cephalotaxine.
Hameed
Abdul
A
The School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
Blake
Alexander J
AJ
Hayes
Christopher J
CJ
D003978:Diazomethane / Q000031:analogs & derivatives / Q000737:chemistry; D006248:Harringtonines / Q000138:chemical synthesis*; D000077863:Homoharringtonine; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D013237:Stereoisomerism; D017971:Tin Compounds / Q000737:chemistry; D014297:Trimethylsilyl Compounds / Q000737:chemistry
C451480:(trimethylsilyl)diazaomethane; D006248:Harringtonines; D017971:Tin Compounds; D014297:Trimethylsilyl Compounds; C030011:carbene; D003978:Diazomethane; C041694:stannic chloride; D000077863:Homoharringtonine; D011392:Proline; D008697:Methane