Enantiospecific synthesis of carbapentostatins.
In this paper we describe enantioselective syntheses of (+)-carbapentostatin (8) and its cyclopentyl analogue 12b. A new and efficient one-pot, two-step preparation of aldehyde 15 has been developed, based on the borane reduction of N-Pf-protected L-aspartic acid gamma-methyl ester (13) and Swern oxidation of the resulting alcohol. Homologation to diester 18 and ring formation by Dieckman cyclization, followed by reduction and dehydration steps, afford the 4-amino-1-cyclopentenemethanol derivative 22. Hydroboration and oxidation transform this compound stereospecifically into aminocyclopentanol 26, the key aminocyclitol component for an asymmetric synthesis of (+)-carbapentostatin.
Ho
Jonathan Z
JZ
Department of Chemistry, University of California, Berkeley, California 94720, USA. jonathan_ho@merck.com
Mohareb
Rafat M
RM
Ahn
Jin Hee
JH
Sim
Tae Bo
TB
Rapoport
Henry
H
D003070:Coformycin / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D015394:Molecular Structure; D015649:Pentostatin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
C474412:carbapentostain; D003070:Coformycin; D015649:Pentostatin