Asymmetric synthesis and biological evaluation of natural or bioinspired cytotoxic C2-symmetrical lipids with two terminal chiral alkynylcarbinol pharmacophores.
J Org Chem
; 80(11): 5386-94, 2015 Jun 05.
Article
em En
| MEDLINE
| ID: mdl-25961794
ABSTRACT
Bidirectional syntheses of C2-symmetrical lipids embedding two terminal alkynylcarbinol pharmacophores are reported. Naturally occurring chiral alkenylalkynylcarbinol units were generated using Pu's procedure for enantioselective addition of terminal alkynes to aldehydes, allowing the first asymmetric synthesis of (3R,4E,16E,18R)-icosa-4,16-diene-1,19-diyne-3,18-diol, isolated from Callyspongia pseudoreticulata. Two synthetic analogues embedding the recently uncovered (S)-dialkynylcarbinol pharmacophore were secured using Carreira's procedure adapted to ynal substrates. The dramatic effect of the carbinol configuration on cytotoxicity was confirmed with submicromolar IC50 values against HCT116 cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metanol
/
Alcinos
/
Di-Inos
/
Lipídeos
Limite:
Humans
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
França