Design and total synthesis of unnatural analogues of the sub-nanomolar SERCA inhibitor thapsigargin

Stephen P. Andrews; Malcolm M. Tait; Matthew Ball; Steven V. Ley

doi:10.1039/B702481A

Design and total synthesis of unnatural analogues of the sub-nanomolar SERCA inhibitor thapsigargin

Stephen P. Andrews,^a Malcolm M. Tait,^a^b Matthew Ball^a and Steven V. Ley*^a

* Corresponding authors

^a University Chemical Laboratory, Lensfield Road, Cambridge, UK
E-mail: svl1000@cam.ac.uk
Web: http://leygroup.ch.cam.ac.uk
Fax: +44 (0)1223 336442
Tel: +44 (0)1223 336398

^b GI Medicinal Chemistry, Neurology and GI CEDD, GlaxoSmithKline, New Frontiers Science Park (North), Third Avenue, Essex, Harlow, UK

Abstract

Thapsigargin is a densely oxygenated guaianolide which displays potent sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA) binding affinities. The total syntheses of designed unnatural analogues of this important natural product are described. This article constitutes the chemical synthesis behind an ongoing project. Rational modifications have been made to the lactone region of thapsigargin in order to obtain derivatives for future structure–activity relationship studies.

Supplementary files

Publication details

The article was received on 15 Feb 2007, accepted on 07 Mar 2007 and first published on 23 Mar 2007

Article type: Paper

DOI: 10.1039/B702481A

Citation: Org. Biomol. Chem., 2007,5, 1427-1436

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Design and total synthesis of unnatural analogues of the sub-nanomolar SERCA inhibitor thapsigargin

S. P. Andrews, M. M. Tait, M. Ball and S. V. Ley, Org. Biomol. Chem., 2007, 5, 1427
DOI: 10.1039/B702481A
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Organic & Biomolecular Chemistry

Design and total synthesis of unnatural analogues of the sub-nanomolar SERCA inhibitor thapsigargin

Abstract

Supplementary files

Publication details

Design and total synthesis of unnatural analogues of the sub-nanomolar SERCA inhibitor thapsigargin

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