A Synthetic Route to Fully Substituted Chiral Cyclopentylamine Derivatives: Precursors of Carbanucleosides

Abstract

Removal of silyl protection from d-glucose derived substrate 6 afforded 7, which upon acetonide deprotection followed by reaction with N-benzylhydroxylamine furnished two isomeric isoxazolidinocyclopentane derivatives via spontaneous cyclization of an in situ generated nitrone. The methyl xanthate derivative of the tertiary hydroxyl group of one isomer was isolated and subjected to radical deoxygenation reaction to form epimeric products, while with the other isomer it underwent spontaneous 1,2-elimination to form a mixture of the two possible endocyclic olefins. Hydrogenolytic cleavage of the isoxazolidine rings of the purified products followed by insertion of 5-amino-4-chloropyrimidine moiety and purine ring construction smoothly afforded structurally unique carbanucleoside analogues. Various spectroscopic methods on the synthesized compounds and X-ray analysis on one important intermediate were used to assign the structures and stereochemistry of the products.

Key words

cyclopentylamine - INC reaction - carbanucleosides - d-glucose

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22

We tried several times to cleave the isoxazolidine ring in addition to reducing the double bond of 19 by hydrogenation reaction, but every time only the double bond was reduced. In contrast, successful isoxazolidine ring cleavage occurred in the cases of 9 and 10. We do not have an explanation for this.

24

Crystal data for 9 have been deposited at the Cambridge Crystallographic Data Centre with reference number CCDC 750271. Data can be obtained via www.ccdc.cam.ac.uk/data_request/cif.