The synthesis of 4-alkylsulphonyl-5-amino- and 5-amino-4-phosphono- imidazole nucleosides as potential inhibitors of purine biosynthesis

J. Grant Buchanan, Avril E. McCaig, Richard H. Wightman

Research output: Contribution to journalArticle

Abstract

Conversion of 4(5)-methylthio-5(4)-nitroimidazole (11) into its silyl derivative and subsequent condensation with 1-O-acetyl-2,3,5-tri-O-benzoyl- ß-D-ribofuranose (9) in the presence of trimethylsilyl trifluoromethanesulphonate for a short reaction time gave 4-methylthio-5-nitro- 1-(2,3,5-tri-O-benzoyl-ß-D-ribofuranosyl)imidazole (15) with high regioselectivity; use of longer reaction times gave predominantly the 5-methylthio-4-nitro-isomer (14). 5-Amino-4-methylsulphonyl-1-ß-D- ribofuranosyl)imidazole (7) was obtained from (15) in three steps. Similar chemistry was used to prepare 5-amino-4-[(carboxarnido)methyl]sulphonyl-1- ß-D-ribofuranosylimidazole (8), 5-[(diethylphosphono)methyl]thio-4-nitro-1- (2,3,5-tri-O-benzoyl-ß-D-ribofuranosyl)imidazole (26), and 4-{[2,3-bis(methoxycarbonyl)propyl]thio}-5-nitro-1 -(2,3,5-tri-O-benzoyl-ß- D-ribofuranosyl)imidazole (29). Desulphurization of 3',5'-di-O-t- butyldimethylsilyl-ß-D-arabinofurano[1',2':4,5] oxazolidine-2-thione (33) and subsequent interaction with diethyl a-amino-cyanomethyl phosphonate (32) gave, after desilylation, 5-amino-4-diethylpnosphono-1 -(ß-D-arabinofuranosyl)imidazole (36).

Original languageEnglish
Pages (from-to)955-963
Number of pages9
JournalJournal of the Chemical Society, Perkin Transactions 1
Issue number4
Publication statusPublished - 1990

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Biosynthesis
Nucleosides
Thiones
Regioselectivity
Organophosphonates
Isomers
Condensation
imidazole
purine
Derivatives

Cite this

@article{6e2d644dd50e4682bde7475865440bdb,
title = "The synthesis of 4-alkylsulphonyl-5-amino- and 5-amino-4-phosphono- imidazole nucleosides as potential inhibitors of purine biosynthesis",
abstract = "Conversion of 4(5)-methylthio-5(4)-nitroimidazole (11) into its silyl derivative and subsequent condensation with 1-O-acetyl-2,3,5-tri-O-benzoyl- {\ss}-D-ribofuranose (9) in the presence of trimethylsilyl trifluoromethanesulphonate for a short reaction time gave 4-methylthio-5-nitro- 1-(2,3,5-tri-O-benzoyl-{\ss}-D-ribofuranosyl)imidazole (15) with high regioselectivity; use of longer reaction times gave predominantly the 5-methylthio-4-nitro-isomer (14). 5-Amino-4-methylsulphonyl-1-{\ss}-D- ribofuranosyl)imidazole (7) was obtained from (15) in three steps. Similar chemistry was used to prepare 5-amino-4-[(carboxarnido)methyl]sulphonyl-1- {\ss}-D-ribofuranosylimidazole (8), 5-[(diethylphosphono)methyl]thio-4-nitro-1- (2,3,5-tri-O-benzoyl-{\ss}-D-ribofuranosyl)imidazole (26), and 4-{[2,3-bis(methoxycarbonyl)propyl]thio}-5-nitro-1 -(2,3,5-tri-O-benzoyl-{\ss}- D-ribofuranosyl)imidazole (29). Desulphurization of 3',5'-di-O-t- butyldimethylsilyl-{\ss}-D-arabinofurano[1',2':4,5] oxazolidine-2-thione (33) and subsequent interaction with diethyl a-amino-cyanomethyl phosphonate (32) gave, after desilylation, 5-amino-4-diethylpnosphono-1 -({\ss}-D-arabinofuranosyl)imidazole (36).",
author = "Buchanan, {J. Grant} and McCaig, {Avril E.} and Wightman, {Richard H.}",
year = "1990",
language = "English",
pages = "955--963",
journal = "Journal of the Chemical Society, Perkin Transactions 1",
issn = "1472-7781",
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}

The synthesis of 4-alkylsulphonyl-5-amino- and 5-amino-4-phosphono- imidazole nucleosides as potential inhibitors of purine biosynthesis. / Buchanan, J. Grant; McCaig, Avril E.; Wightman, Richard H.

In: Journal of the Chemical Society, Perkin Transactions 1, No. 4, 1990, p. 955-963.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The synthesis of 4-alkylsulphonyl-5-amino- and 5-amino-4-phosphono- imidazole nucleosides as potential inhibitors of purine biosynthesis

AU - Buchanan, J. Grant

AU - McCaig, Avril E.

AU - Wightman, Richard H.

PY - 1990

Y1 - 1990

N2 - Conversion of 4(5)-methylthio-5(4)-nitroimidazole (11) into its silyl derivative and subsequent condensation with 1-O-acetyl-2,3,5-tri-O-benzoyl- ß-D-ribofuranose (9) in the presence of trimethylsilyl trifluoromethanesulphonate for a short reaction time gave 4-methylthio-5-nitro- 1-(2,3,5-tri-O-benzoyl-ß-D-ribofuranosyl)imidazole (15) with high regioselectivity; use of longer reaction times gave predominantly the 5-methylthio-4-nitro-isomer (14). 5-Amino-4-methylsulphonyl-1-ß-D- ribofuranosyl)imidazole (7) was obtained from (15) in three steps. Similar chemistry was used to prepare 5-amino-4-[(carboxarnido)methyl]sulphonyl-1- ß-D-ribofuranosylimidazole (8), 5-[(diethylphosphono)methyl]thio-4-nitro-1- (2,3,5-tri-O-benzoyl-ß-D-ribofuranosyl)imidazole (26), and 4-{[2,3-bis(methoxycarbonyl)propyl]thio}-5-nitro-1 -(2,3,5-tri-O-benzoyl-ß- D-ribofuranosyl)imidazole (29). Desulphurization of 3',5'-di-O-t- butyldimethylsilyl-ß-D-arabinofurano[1',2':4,5] oxazolidine-2-thione (33) and subsequent interaction with diethyl a-amino-cyanomethyl phosphonate (32) gave, after desilylation, 5-amino-4-diethylpnosphono-1 -(ß-D-arabinofuranosyl)imidazole (36).

AB - Conversion of 4(5)-methylthio-5(4)-nitroimidazole (11) into its silyl derivative and subsequent condensation with 1-O-acetyl-2,3,5-tri-O-benzoyl- ß-D-ribofuranose (9) in the presence of trimethylsilyl trifluoromethanesulphonate for a short reaction time gave 4-methylthio-5-nitro- 1-(2,3,5-tri-O-benzoyl-ß-D-ribofuranosyl)imidazole (15) with high regioselectivity; use of longer reaction times gave predominantly the 5-methylthio-4-nitro-isomer (14). 5-Amino-4-methylsulphonyl-1-ß-D- ribofuranosyl)imidazole (7) was obtained from (15) in three steps. Similar chemistry was used to prepare 5-amino-4-[(carboxarnido)methyl]sulphonyl-1- ß-D-ribofuranosylimidazole (8), 5-[(diethylphosphono)methyl]thio-4-nitro-1- (2,3,5-tri-O-benzoyl-ß-D-ribofuranosyl)imidazole (26), and 4-{[2,3-bis(methoxycarbonyl)propyl]thio}-5-nitro-1 -(2,3,5-tri-O-benzoyl-ß- D-ribofuranosyl)imidazole (29). Desulphurization of 3',5'-di-O-t- butyldimethylsilyl-ß-D-arabinofurano[1',2':4,5] oxazolidine-2-thione (33) and subsequent interaction with diethyl a-amino-cyanomethyl phosphonate (32) gave, after desilylation, 5-amino-4-diethylpnosphono-1 -(ß-D-arabinofuranosyl)imidazole (36).

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EP - 963

JO - Journal of the Chemical Society, Perkin Transactions 1

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SN - 1472-7781

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