Issue 8, 2012

Biosynthetic medicinal chemistry of natural product drugs

Abstract

Natural products are an unsurpassed source of lead structures for drug discovery. However, these molecules, many of which fall into the beyond-rule-of-5 chemical space, are often difficult to optimize by chemical means because of their complex structures. Biosynthetic engineering of the producing host organism offers an important tool for the modification of complex natural products, leading to analogues which are unattainable by chemical semisynthesis. This review describes the current role of natural products in lead generation and the principles behind biosynthetic medicinal chemistry. It then goes on to describe five distinct drugs – salinosporamide, geldanamycin, FK506, rapamycin and epothilone – to exemplify how biosynthetic engineering approaches have contributed to the advancement of natural product clinical candidates.

Graphical abstract: Biosynthetic medicinal chemistry of natural product drugs

Supplementary files

Article information

Article type
Review Article
Submitted
22 Dec 2011
Accepted
20 Feb 2012
First published
19 Mar 2012

Med. Chem. Commun., 2012,3, 854-865

Biosynthetic medicinal chemistry of natural product drugs

F. E. Koehn, Med. Chem. Commun., 2012, 3, 854 DOI: 10.1039/C2MD00316C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Spotlight

Advertisements