Issue 30, 2012

Photochemical oxazole–nitrile conversion downstream of rhizoxin biosynthesis and its impact on antimitotic activity

Abstract

Through metabolic profiling of mutants and wild type of the endofungal bacterium Burkholderia rhizoxinica two novel rhizoxin derivatives with unusual nitrile substitutions were discovered. The nitrile groups result from a photochemical oxidative cleavage of the oxazolyl moiety. In vitro studies revealed that the photooxidation by singlet oxygen also takes place in the absence of a photosensitizer, and that also a thiazolyl-substituted rhizoxin analogue undergoes the same transformation. The resulting nitriles have antimitotic properties but are significantly less active than the parent compounds. These results highlight the impact of photoreactions onto the antiproliferative agent and encourage the introduction of bioisosteric groups that render the compound less susceptible towards photooxidation.

Graphical abstract: Photochemical oxazole–nitrile conversion downstream of rhizoxin biosynthesis and its impact on antimitotic activity

Supplementary files

Article information

Article type
Communication
Submitted
02 ፌብሩ 2012
Accepted
12 ማርች 2012
First published
12 ማርች 2012

Org. Biomol. Chem., 2012,10, 5756-5759

Photochemical oxazolenitrile conversion downstream of rhizoxin biosynthesis and its impact on antimitotic activity

K. Scherlach, N. Brendel, K. Ishida, H. Dahse and C. Hertweck, Org. Biomol. Chem., 2012, 10, 5756 DOI: 10.1039/C2OB25250C

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.

Social activity

Spotlight

Advertisements