Total Synthesis of (-)-Agelastatin

metathesis - sulfinimines - 1,2-addition

Significance

The target molecule was isolated from the sponge Agelas dedromorpha. It is active against several tumour cell lines and it inhibits glycogen synthase kinase-3β. It has potential for the treatment of Alzheimer’s disease, the prevention of neuronal apoptosis after stroke and it could function as an insulin mimetic.

Comment

The asymmetric synthesis of the 4,5-diaminocyclopenten-2-one derivative D entailed (a) nucleophilic addition of the lithium enolate of N,N-dibenzylglycine (5 equiv) to the homochiral sulfinimine A and (b) a ring closing metathesis of C. The nucleophilic addition step gave three of the four possible diastereoisomers (dr 18:1:5:0) with the major diastereoisomer B being the major product, isolated in 73% yield.