CHIROSPECIFIC SYNTHESIS OF (1S,3R)-1-AMINO-3-(HYDROXYMETHYL)CYCLOPENTANE, PRECURSOR FOR CARBOCYCLIC NUCLEOSIDE SYNTHESIS - DIECKMANN CYCLIZATION WITH AN ALPHA-AMINO-ACID

Carbocyclic nucleosides are important isosteres of nucleosides possess ing a variety of antiviral and antineoplastic activities. We report he re a new method for the chirospecific synthesis of (1S,3R)-1-amino-3-( hydroxymethyl)cyclopentane. This compound is a key precursor for the s ynthesis of some carbocyclic nucleosides. The method involves (1) an i mproved synthesis of (S)-2-aminoadipic acid; (2) Dieckmann cyclization of this alpha-amino acid to an aminocyclopentanone; and (3) elaborati on of the latter to the target (1S,3R)-l-amino-3-(hydroxymethyl)cyclop entane. The starting (S)-2-aminoadipic acid delta-methyl ester was pre pared enantiomerically pure from (S)-aspartic acid in 51% overall yiel d. Dieckmann condensation converted this amino acid to a (methoxycarbo nyl)-cyclopentanone, and reduction of the ketone followed by eliminati on yielded uoren-9-yl)amino]-1-(methoxycarbonyl)cyclopentene. Reductio n of the double bond gave a mixture of the cis and trans diastereomers . This mixture was converted to a single diastereomer by epimerization and trapping of the cis isomer as enylfluoren-9-yl)-2-azabicyclo[2.2. 1]heptan-3-one. Hydrolytic cleavage of the lactam followed by reductio n gave (IS,3R)-1-amino-3-(hydroxymethyl)-cyclopentane.