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Salinosporamide A is a potent 20S-proteasome inhibitor used anticancer agent that recently entered phase I human clinical trials for the treatment of multiple myeloma only 3 years after its discovery <ref name="pmid12548698">{{cite journal |author=Feling RH, Buchanan GO, Mincer TJ, Kauffman CA, Jensen PR, Fenical W |title=Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora |journal=Angew. Chem. Int. Ed. Engl. |volume=42 |issue=3 |pages=355-7 |year=2003 |pmid=12548698 |doi=10.1002/anie.200390115}}</ref><ref name="pmid16286248">{{cite journal |author=Chauhan D, Catley L, Li G, ''et al'' |title=A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib |journal=Cancer Cell |volume=8 |issue=5 |pages=407-19 |year=2005 |pmid=16286248 |doi=10.1016/j.ccr.2005.10.013}}</ref>. This novel marine natural product is produced by the recently described obligate marine bacterium ''Salinispora tropica'' and belongs to a family of compounds possesing a densely functionalized γ-lactam-βlactone bicycle(ref).
==History==
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==Biosynthesis==
It was originally hypothesized that Salinosporamide B was a biosynthetic precursor to Salinosporamide A due to their structural similarities. The halogenation of the unactivated methyl group being catalyzed by a non-heme iron halogenase<ref name="pmid17274624">{{cite journal |author=Beer LL, Moore BS |title=Biosynthetic convergence of salinosporamides A and B in the marine actinomycete Salinispora tropica |journal=Org. Lett. |volume=9 |issue=5 |pages=845-8 |year=2007 |pmid=17274624 |doi=10.1021/ol063102o}}</ref><ref name="pmid16895332">{{cite journal |author=Vaillancourt FH, Yeh E, Vosburg DA, Garneau-Tsodikova S, Walsh CT |title=Nature's inventory of halogenation catalysts: oxidative strategies predominate |journal=Chem. Rev. |volume=106 |issue=8 |pages=3364-78 |year=2006 |pmid=16895332 |doi=10.1021/cr050313i}}</ref>. Recent work using <sup>13</sup>C labeled feeding experiments reveal distinct biosynthetic origins of salinosporamide A and B.<ref name="pmid17274624">{{cite journal |author=Beer LL, Moore BS |title=Biosynthetic convergence of salinosporamides A and B in the marine actinomycete Salinispora tropica |journal=Org. Lett. |volume=9 |issue=5 |pages=845-8 |year=2007 |pmid=17274624 |doi=10.1021/ol063102o}}</ref><ref name="pmid17340108">{{cite journal |author=Tsueng G, McArthur KA, Potts BC, Lam KS |title=Unique butyric acid incorporation patterns for salinosporamides A and B reveal distinct biosynthetic origins |journal= |volume= |issue= |pages= |year=2007 |pmid=17340108 |doi=10.1007/s00253-007-0899-7}}</ref>
[[Image:Salinosporamide_A_building_blocks.png|thumb|Salinosporamide A building Blocks]]
[[Image:Biosynthesis of nonproteinogenic amino acid.png|thumb|Biosynthesis of nonproteinogenic amino acid]]
==Total Synthesis==
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