Salinosporamide A

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Structural formula
Structural formula of salinosporamide A
General
Non-proprietary name Marizomib
other names
  • (4 R , 5 S ) -4- (2-chloroethyl) -1 - ((1 S ) -cyclohex-2-enyl (hydroxy) methyl) -5-methyl-6-oxa-2-azabicyclo [3.2.0 ] heptane-3,7-dione
  • NPI-0052
Molecular formula C 15 H 20 ClNO 4
External identifiers / databases
CAS number 437742-34-2
PubChem 11347535
ChemSpider 9522473
DrugBank DB11762
Wikidata Q7404722
properties
Molar mass 313.781 g mol −1
safety instructions
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Salinosporamide A is a natural product that was isolated from bacteria of the species Salinispora tropica and Salinispora arenicola that occur in marine sediments . Chemically, the compound is a highly functionalized γ- lactam -β- lactone . The compound acts as a proteasome inhibitor and is being investigated in clinical tests for its effectiveness as an anti-cancer agent .

history

Salinosporamide A was discovered in 2003. The compound belongs to a family of compounds called salinosporamides. In screening tests , this group of substances showed high in vitro cytotoxicity against various types of carcinoma. It was found that salinosporamide A influences cell growth by blocking the proteasome enzyme.

Mechanism of action

The mechanism of action of salinosporamide could be elucidated by X-ray structure analysis of the proteasome. The chlorine atom plays a key role here, as it triggers an internal cyclization reaction by splitting off.

Manufacturing

The first total synthesis was achieved by EJ Corey's group in 2004. Starting from ( S ) -threonine methyl ester, the synthesis takes place in six steps.

Individual evidence

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. Jump up ↑ Robert H. Feling, Greg O. Buchanan, Tracy J. Mincer, Christopher A. Kauffman, Paul R. Jensen, William Fenical: Salinosporamide A: A Highly Cytotoxic Proteasome Inhibitor from a Novel Microbial Source, a Marine Bacterium of the New Genus Salinospora. In: Angewandte Chemie International Edition. 42, 2003, pp. 355-357, doi : 10.1002 / anie.200390115 .
  3. ↑ Lyudmila Borissenko, Michael Groll: 20S Proteasome and Its Inhibitors: Crystallographic Knowledge for Drug Development. In: Chemical Reviews. 107, 2007, pp. 687-717, doi : 10.1021 / cr0502504 .
  4. ↑ Elucidation of the mechanism of a proteasome inhibition by salinosporamide A. In: Portal für Organische Chemie. Retrieved December 31, 2013 .
  5. ↑ Leleti Rajender Reddy, P. Saravanan, EJ Corey: A Simple Stereocontrolled Synthesis of Salinosporamide A. In: Journal of the American Chemical Society. 126, 2004, pp. 6230-6231, doi : 10.1021 / ja048613p .
  6. ↑ Synthesis of the Proteasome Inhibitors Salinosporamide A, Omuralide and Lactacystin. In: Organic Chemistry Portal. Retrieved December 31, 2013 .