Asymmetric synthesis of dialkyloxy-3-alkylammonium cationic lipids.
J Org Chem
; 69(3): 980-3, 2004 Feb 06.
Article
em En
| MEDLINE
| ID: mdl-14750834
ABSTRACT
The cationic diether-linked cytofectin DOTMA (available commercially as a mixture, Lipofectin comprised of DOTMADOPE, 11) and analogues including DIMRIE and DORIE are frequently used for in vitro and in vivo transfections. Despite this wide usage direct synthetic routes to the optical isomers have received little attention to date. Here we describe strategies to synthesize enantiomers of DOTMA and analogues, including an extremely concise procedure to the trimethylammonium salts. One strategy utilized N-protection, as the imine, with concomitant ether formation and deprotection during the workup. Methylation of the 1-amino-2,3-dialkyloxypropane then generated the trimethylammonium cationic lipids directly. This methodology was extended to synthesize a novel headgroup functionalized lipid. A second route was also developed using an alternative chiral synthon.
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Base de dados:
MEDLINE
Assunto principal:
Compostos de Amônio Quaternário
/
Lipídeos
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article