Salinosporamide A

(4R,5S)-4-(2-chloroethyl)-1-((1S)-cyclohex-2-enyl(hydroxy)methyl)-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptan-3,7-dion

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Salinosporamide A is a natural compound that has been isolated from occurring in marine sediment bacteria of the species Salinispora tropica and Salinispora arenicola. Chemically, the compound is a highly functionalized γ β -lactam -lactone. The compound acts as a proteasome inhibitor, and is being investigated in clinical trials for efficacy as an anticancer agent.

History

Salinosporamide A was discovered in 2003. The compound belongs to a family of compounds, referred to as Salinosporamide. In screening experiments this substance group showed high in vitro cytotoxicity against various cancer types. It was found that the salinosporamide A affects cell growth by blocking the enzyme proteasome.

Mechanism of Action

X-ray crystallographic analysis of the mechanism of action of the proteasome Salinosporamids could be elucidated. A key component of this case has the chlorine atom, which triggers cleavage by an internal cyclization reaction.

Production

The first total synthesis was the group of EJ Corey in 2004. Starting from ( S)- threonine methyl ester, the synthesis in a six stages.