Stereoselective formation of a functionalized dipeptide isostere by zinc carbenoid-mediated chain extension.
The application of a zinc carbenoid-mediated chain-extension reaction to a functionalized peptide isostere is reported. The cleavage site of human CVM protease was utilized as a target for testing the synthetic methodology. The utility of this chain-extension reaction is demonstrated in the preparation of an amino acid-derived alpha-unsubstituted gamma-keto ester, which is incorporated into a framework that mimics a tetrapeptide. The identification of a suitable protecting group strategy facilitated the application of a tandem reaction for the incorporation of an alpha-side chain, and the use of an oxazolidinone auxiliary provided excellent diastereocontrol in a tandem chain-extension-aldol reaction. Stereoselectivity of the tandem chain-extension-aldol reaction was determined through application of a CAN-mediated oxidative cleavage reaction.
Lin
Weimin
W
Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, USA.
Theberge
Cory R
CR
Henderson
Timothy J
TJ
Zercher
Charles K
CK
Jasinski
Jerry
J
Butcher
Ray J
RJ
D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D020134:Catalytic Domain; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
D004151:Dipeptides; D009942:Organometallic Compounds; D012697:Serine Endopeptidases; C071910:assemblin; C454811:diethylzinc