Highly Stereoselective Total Synthesis of the Natural Leukotriene (-)-(5S,6S)-LTA4 Methyl Ester and of Its η-7-10 (Tricarbonyl) Iron Complex

Michel Franck-Neumann; Pierre-Jean Colson

doi:10.1055/s-1991-20913

Synlett 1991; 1991(12): 891-894
DOI: 10.1055/s-1991-20913

letter

© Georg Thieme Verlag, Rüdigerstr. 14, 70469 Stuttgart, Germany. All rights reserved. This journal, including all individual contributions and illustrations published therein, is legally protected by copyright for the duration of the copyright period. Any use, exploitation or commercialization outside the narrow limits set by copyright legislation, without the publisher's consent, is illegal and liable to criminal prosecution. This applies in particular to photostat reproduction, copying, cyclostyling, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage.

Highly Stereoselective Total Synthesis of the Natural Leukotriene (-)-(5S,6S)-LTA₄ Methyl Ester and of Its η-7-10 (Tricarbonyl) Iron Complex

Michel Franck-Neumann^* , Pierre-Jean Colson

^*Laboratoire de Chimie Organique Synthétique, Associé au CNRS (URA no 466), Institut de Chimie, Université Louis Pasteur, 1 rue Blaise Pascal, F-67008 Strasbourg, France

Abstract

PDF Download All articles of this category

The optically active (ee 96 %) leukotriene (5S,6S,7E,9E,11Z, 14Z)-5,6-epoxy-7,9,11,14-icosatetraenoic acid (LTA₄) methyl ester (-)-12 and the corresponding η-7-10 (tricarbonyl) iron complex (+)-10 have been synthesized in 12 and 11 steps, respectively and in overall yields of 15 % and 18 % starting from tricarbonyl[methyl (R)-2-5-η-penta-2,4-dienoate]-iron. The key steps involve Friedel-Crafts acylation of the trichloroethyl ester of the starting complex with methyl 5-(chloroformyl)pentanoate, stereoselective transformation into the α-chlorodienone complex (+)-3a, followed by subsequent transformation of the trichloroethyl ester into an aldehyde. Wittig reaction with the known (Z)-(3-nonenylidene)triphenylphosphorane afforded the optically pure (ee 99 %) (tricarbonyl) iron complex (+)-9, possessing the entire functionalized carbon skeleton of the LTA₄ methyl ester. This common intermediate was readily converted to the LTA₄ methyl ester (-)-12, or its Fe(CO)₃ complex (+)-10.

PDF (292 kb)