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

Marine Drugs

Barbara C. Potts¹ 

关键词: salinosporamide A;    marizomib;    NPI-0052;    proteasome inhibitor;    total synthesis;    semi-synthesis;    natural products chemistry;    fermentation;    mutasynthesis;    precursor-directed biosynthesis;    structure-activity relationships;    analogs;   

DOI  :  10.3390/md8040835

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland