Total synthesis of (-)-neplanocin A by using lithium thiolate-initiated Michael-Aldol tandem cyclization reaction

(-)-Neplanocin A (1), S-adenosylhomocystein hydrolase inhibitor, was synthe sized. The characteristic of this synthesis is a stereoselective constructi on of five-membered ring of neplanocin A by intramolecular aldol reaction o f the lithium enolate that was generated by conjugate addition of lithium t hiolate. TBS-protected chiral omega -oxo-alpha,beta -unsaturated ester 16, which was prepared from D-mannitol, was treated with 1.2 equiv of lithium b enzylthiolate in THF at -20 degreesC to give three separable cyclization pr oducts in good yields and stereoselectivity. After conversions of protectiv e groups, the benzylsulfanyl part of 21 was removed by oxidation to sulfoxi de and subsequent thermal elimination to give the requisite double bond. Th rough the functional group transformations of 30, total synthesis of (-)-ne planocin A (1) was accomplished.