Synfacts 2005(0): 0012-0012  
DOI: 10.1055/s-2005-865348
Synthesis of Natural Products and Drugs
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of (-)-Agelastatin

Contributor(s): Philip Kocienski
F. A. Davis*, J. Deng
Temple University, Philadelphia, USA
Asymmetric Total Synthesis of (-)-Agelastatin A Using Sulfinimine (N-Sulfinyl Imine) Derived Methodologies
Org. Lett.  2005,  7:  621-623  
Further Information

Publication History

Publication Date:
20 July 2005 (online)


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.