View : 19 Download: 0

Synthesis of cyclopropyl-fused carbocyclic nucleosides via the regioselective opening of cyclicsulfi sulfites

Title
Synthesis of cyclopropyl-fused carbocyclic nucleosides via the regioselective opening of cyclicsulfi sulfites
Authors
Moon H.R.Kim H.O.Chun M.W.Jeong L.S.Marquez V.E.
Ewha Authors
정낙신
Issue Date
1999
Journal Title
Journal of Organic Chemistry
ISSN
0022-3263JCR Link
Citation
vol. 64, no. 13, pp. 4733 - 4741
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The syntheses of some carbocyclic nucleosides that are conformationally locked as 'northern' mimics of antiviral active, ring-expanded oxetanocin analogues are reported. The target compounds derived their rigid conformation from a common bicyclo[3.1.0]hexane template. The uracil (3a), cytosine (3b), and adenine (3c) analogues were synthesized from an intermediate cyclic sulfite (12a) that underwent selective ring opening with nucleophiles. Reaction of 12a with sodium azide provided access to the uracil and cytosine analogues (3a and 3b) after construction of the pyrimidine rings, and reaction with the sodium salt of adenine provided an efficient convergent approach to 3c. The preponderance of the undesired N-7 regioisomer obtained from the coupling of 12a with 2-amino-6-chloropurine was unanticipated: Hence, the diol derivative 11 was selectively protected and coupled under Mitsunobu conditions to give, after deprotection, the desired guanine analogue 3d. With the exception of the guanine analogue, the cyclic sulfite chemistry described here represents a useful alternative as a general approach to carbocyclic nucleosides. None of the target nucleosides 3a-d demonstrated significant antiviral activity against HIV-1, HSV-1, HSV-2, and HCMV. Relative to other conformationally rigid, northern carbocyclic analogues that have shown good anti-HSV and anti-HCMV activities, it is concluded that the hydroxymethyl group is a poor substitute for the hydroxyl group in these rigid bicyclic nucleoside templates.
DOI
10.1021/jo990010m
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE