Synthesis of 1-methyl-5-(3-azido-2,3-dideoxy-ß-D-erythro-pentofuranosyl)uracil and 1-methyl-5-(3-azido-2,3-dideoxy-2-fluoro-ß-D-arabinofuranosyl)uracil. The C-nucleoside isostere of 3'-azido-3'-deoxythymidine and its 2'-"up"-fluoro analogue Journal Article

  

Authors:	Sochacka, E.; Nawrot, B.; Pankiewicz, K. W.; Watanabe, K. A.
Article Title:	Synthesis of 1-methyl-5-(3-azido-2,3-dideoxy-ß-D-erythro-pentofuranosyl)uracil and 1-methyl-5-(3-azido-2,3-dideoxy-2-fluoro-ß-D-arabinofuranosyl)uracil. The C-nucleoside isostere of 3'-azido-3'-deoxythymidine and its 2'-"up"-fluoro analogue
Abstract:	l-Methyl-5-(3-azido-2,3-dideoxy-jft-D-ery£hro-pentofuranosyl)uracil (C-AZT), a C-nucleoside isostere of the potent anti-AIDS nucleoside 3'-azido-3’-deoxythymidine (AZT), was synthesized. 1 - Methyl- 2/-deoxy-5/- O-tri tylpseudouridine (2a) was oxidized with Cr03/pyridine/Ac20 complex to l-methyl-5-(5-0-trityl-/?-D-£fycero-pentofuranos-3-ulosyl)uracil (12a), which was selectively reduced to l-methyl-5-(5-0-trityl-/3-D-£hreo-pentofuranosyl)uracil (13a). Mesylation of 13a to 14a followed by nucleophilic displacement of the mesyloxy group with azide afforded 3'-azido-2',3'-dideoxy-S'-O-trityl-l-methylpseudoridine (15a), which was detritylated to C-AZT. In a similar manner, 1-methyl-5-(2-deoxy-2-fluoro-£-D-arabinofuranosyl)uracil (C-FMAU, a potent antiherpetic nucleoside) was converted into the 3’-azido analogue (3'-azido-C-FMAU). Both C-AZT and S’-azido-C-FMAU, however, did not exhibit any significant inhibitory activity against HIV in H9 cells. © 1990, American Chemical Society. All rights reserved.
Keywords:	unclassified drug; nonhuman; mass spectrometry; cell line; drug structure; drug screening; drug synthesis; structure-activity relationship; cell culture; magnetic resonance spectroscopy; molecular structure; human immunodeficiency virus; nuclear magnetic resonance; hiv; zidovudine; antiviral agents; indicators and reagents; microbial sensitivity tests; human; priority journal; article; spectrum analysis, mass; 5 (3 azido 2,3 dideoxy 2 fluoro beta d arabinofuranosyl) 1 methyluracil; 5 (3 azido 2,3 dideoxy beta d erythro pentofuranosyl) 1 methyluracil
Journal Title:	Journal of Medicinal Chemistry
Volume:	33
Issue:	7
ISSN:	0022-2623
Publisher:	American Chemical Society
Date Published:	1990-07-01
Start Page:	1995
End Page:	1999
Language:	English
DOI:	10.1021/jm00169a030
PUBMED:	2362280
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0025339930&doi=10.1021%2fjm00169a030&partnerID=40&md5=f53900ba3dab2d92e1552cbe1948c315
Notes:	Article -- Export Date: 27 January 2020 -- Source: Scopus

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