CHIROSPECIFIC SYNTHESIS OF (1S,3R)-1-AMINO-3-(HYDROXYMETHYL)CYCLOPENTANE, PRECURSOR FOR CARBOCYCLIC NUCLEOSIDE SYNTHESIS - DIECKMANN CYCLIZATION WITH AN ALPHA-AMINO-ACID
Sc. Bergmeier et al., CHIROSPECIFIC SYNTHESIS OF (1S,3R)-1-AMINO-3-(HYDROXYMETHYL)CYCLOPENTANE, PRECURSOR FOR CARBOCYCLIC NUCLEOSIDE SYNTHESIS - DIECKMANN CYCLIZATION WITH AN ALPHA-AMINO-ACID, Journal of organic chemistry, 58(9), 1993, pp. 2369-2376
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.