Coupling of sterically hindered aldehyde with fluorinated synthons: Stereoselective synthesis of fluorinated analogues of salinosporamide A

Salinosporamide A is an irreversible inhibitor of the β-subunits of the 20S proteasome. Its C-5 cyclohexenyl moiety is the key to its affinity and potency as an anticancer agent. Here we describe the synthesis of C-5 difluoromethylated and trifluoromethylated analogues of salinosporamide A and their...

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Bibliographic Details
Published in:Journal of fluorine chemistry 2012-04, Vol.136, p.12-19
Main Authors: Chen, Zeng-Hao, Wang, Bing-Lin, Kale, Andrew J., Moore, Bradley S., Wang, Ruo-Wen, Qing, Feng-Ling
Format: Article
Language:English
Subjects:
20S proteasome
Affinity
Aldehydes
Anticancer properties
Chemical reactions
Fluorinated analogues
Fluorination
Inhibitors
Salinosporamide A
Strategy
Synthesis (chemistry)
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Summary:Salinosporamide A is an irreversible inhibitor of the β-subunits of the 20S proteasome. Its C-5 cyclohexenyl moiety is the key to its affinity and potency as an anticancer agent. Here we describe the synthesis of C-5 difluoromethylated and trifluoromethylated analogues of salinosporamide A and their biological evaluation as proteasome inhibitors against purified yeast 20S proteasome. The synthetic strategy featured the stereoselective coupling reaction of sterically hindered aldehyde 3 with fluorinated organolithium reagents.
ISSN:0022-1139
1873-3328
DOI:10.1016/j.jfluchem.2012.01.003