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Mar. Drugs 2010, 8(4), 835-880; doi:10.3390/md8040835
Review

Generating a Generation of Proteasome Inhibitors: From Microbial Fermentation to Total Synthesis of Salinosporamide A (Marizomib) and Other Salinosporamides

*  and
Nereus Pharmaceuticals, Inc., 10480 Wateridge Circle, San Diego, CA 92121, USA Present address: Marrone Bio Innovations, 2121 Second Street, Suite B-107, Davis, CA 95618, USA.
* Author to whom correspondence should be addressed.
Received: 28 February 2010 / Revised: 19 March 2010 / Accepted: 22 March 2010 / Published: 25 March 2010
(This article belongs to the Special Issue Synthesis around Marine Natural Products)

Abstract

The salinosporamides are potent proteasome inhibitors among which the parent marine-derived natural product salinosporamide A (marizomib; NPI-0052; 1) is currently in clinical trials for the treatment of various cancers. Methods to generate this class of compounds include fermentation and natural products chemistry, precursor-directed biosynthesis, mutasynthesis, semi-synthesis, and total synthesis. The end products range from biochemical tools for probing mechanism of action to clinical trials materials; in turn, the considerable efforts to produce the target molecules have expanded the technologies used to generate them. Here, the full complement of methods is reviewed, reflecting remarkable contributions from scientists of various disciplines over a period of 7 years since the first publication of the structure of 1.
Keywords: salinosporamide A; marizomib; NPI-0052; proteasome inhibitor; total synthesis; semi-synthesis; natural products chemistry; fermentation; mutasynthesis; precursor-directed biosynthesis; structure-activity relationships; analogs salinosporamide A; marizomib; NPI-0052; proteasome inhibitor; total synthesis; semi-synthesis; natural products chemistry; fermentation; mutasynthesis; precursor-directed biosynthesis; structure-activity relationships; analogs
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Potts, B.C.; Lam, K.S. Generating a Generation of Proteasome Inhibitors: From Microbial Fermentation to Total Synthesis of Salinosporamide A (Marizomib) and Other Salinosporamides. Mar. Drugs 2010, 8, 835-880.

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