ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
An efficient synthesis of the unknown 2′-deoxy-D-threo-tubercidin (1b) and 2′, 3′-dideoxy-3′-fluorotubercidin (2) as well as of the related nucleosides 9a, b and 10b is described. Reaction of 4-chloro-7-(2-deoxy-β-D-erythro-pentofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine (5) with (tert-butyl)diphenylsilyl chloride yielded 6 which gave the 3′-keto nucleoside 7 upon oxidation at C(3′). Stereoselective NaBH4 reduction (→8) followed by deprotection with Bu4NF(→9a)and nucleophilic displacement at C(6) afforded 1b as well as 7-deaza-2′-deoxy-D-threo-inosine (9b). Mesylation of 4-chloro-7-{2-deoxy-5-O-[(tert-butyl)diphenylsilyl]-β-D-threo-pentofuranosyl}-7H-pyrrolo[2,3-d]-pyrimidine (8), treatment with Bu4NF (→12a) and 4-halogene displacement gave 2′, 3′-didehydro-2′, 3′-dideoxy-tubercidin (3) as well as 2′, 3′-didehydro-2′, 3′-dideoxy-7-deazainosne (12c). On the other hand, 2′, 3′-dideoxy-3′-fluorotubercidin (2) resulted from 8 by treatment with diethylamino sulfurtrifluoride (→10a), subsequent 5′-de-protection with Bu4NF (→10b), and Cl/NH2 displacement. 1H-NOE difference spectroscopy in combination with force-field calculations on the sugar-modified tubercidin derivatives 1b, 2, and 3 revealed a transition of the sugar puckering from the 3′T2′ conformation for 1b via a planar furanose ring for 3 to the usual 2′T3′ conformation for 2.
Additional Material:
5 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19890720527
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