Asymmetrische Synthese von Tarchonanthuslacton und Pironetin-Bausteinen

The natural product Pironetin was isolated from the culture broths Streptomyces sp. NK10958 and Streptomyces prunicolor PA-48153 in 1994 and shows remarkably high antitumor and immunosuppressive activity. Aim of this thesis was an efficient asymmetric synthesis of the aforementioned natural product. The keyintermediates in the synthesis are an unsaturated SAMP-hydrazone and an alpha,beta-unsaturated lactone. The SAMP-hydrazone was easily prepared utilizing a stereoselective alpha-alkylation of diethyl SAMP-hydrazone using crotylbromide in good yield (86%) and diastereomeric excess (92%). The other keyintermediate, the alpha,beta-unsaturated lactone resulted from a syn-selective aldol reaction of SAMP-hydrazone and a protected, beta-hydroxy aldehyde with a yield of 85% and a diastereomeric excess of 80%. Auxiliary cleavage followed by methylenation and esterification using acrylic acid furnished a double olefinic substrate for a Grubbs ring-closing metathesis. Furthermore an efficient and straight forward ten-step asymmetric synthesis of the polyketide tarchonanthuslactone in a good overall yield of 21% and excellent diastereomeric and enantiomeric excesses (de, ee >= 96%) has been achieved. The new synthetic route is based on an alpha,beta-unsaturated delta-lactone building block, available in enantiopure form (ee > 99%) by an enzymatic procedure and its conversion to a methyl ketone employing an Umpolung strategy.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2003

Author dc:creator

• Steinbusch, Daniel

Contributors dc:contributor

• Enders, Dieter

• info:eu-repo/classification/ddc/540
• Pironetin
• Totalsynthese
• Asymmetrische Synthese
• Tarchonanthuslacton
• Chemie
• Naturstoffe

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-120862%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:59046