Biography
Biography: Faiza Diaba
Abstract
Daphniphyllum alkaloids, isolated from the Daphniphyllum genus, are a large family of natural compounds containing over than 320 members with more than 20 different polycyclic frameworks.Besides their fascinating structures, many of these compounds have showed a wide range of biological activities naming anticancer, anti-HIV, antioxidant, antiviral, vasorelaxation and nerve growth factor-regulation.Daphenylline, isolated in 2009 from the fruit of D. longeracemosum by Hao and co-workers, is the first member of the Daphniphyllum alkaloids including a benzene ring in the core structure.3 Since its isolation, four total syntheses of daphenylline4 and three other approximations to either the ABCE or the ACDE tetracyclic structures5 were reported. In this investigation we achieved the synthesis of the ACDEF pentacyclic structure of daphenylline from 1-methyl-2-tetralone as a starting material. The synthesis started with the preparation of enamide 1 which underwent a 5-endo-trig radical cyclization in the presence of Bu3SnH and AIBN6 to provide indol 2 with all-carbon quaternary centers present in Daphenylline. Next, a stereocontrolled allylation followed by a diastereoselective reduction of the resulting enamide with NaBH3CN and acetic acid gave 3 embedding the cis-hydroindole structure. Alkene 3 was converted to the corresponding acid using a two steps sequence: i) hydroboration-oxidation, ii) oxidation in the presence of TEMPO and NaClO. The acid was treated with SOCl2 and then submitted to the classical Friedel-Crafts conditions to provide the seven-membered ring in 4 with an excellent yield. After a 1,2-carbonyl transposition of ketone 4 using a four steps sequence, alkylation provided ester 5 with the correct stereochemistry which after a second friedel Crafts cyclization gave 6 with the ACDEF pentacyclic core of daphenylline.