e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

Fluorinated sugar analogs of potential anti-HIV-1 nucleosides

…, LC Chen, L Wang, MH Kim, JA Warshaw…

Index: Huang; Chen; Wang; Kim; Warshaw; Armstrong; Zhu; Chou; Watanabe; Matulic-Adamic; Su; Fox; Polsky; Baron; Gold; Hardy; Zuckerman Journal of Medicinal Chemistry, 1991 , vol. 34, # 5 p. 1640 - 1646

Full Text: HTML

Citation Number: 53

Abstract

In order to obtain agenta with therapeutic indices superior to those of AZT, FLT, or D4T, several analogues of anti-HIV-1 nucleosides were synthesized. These include 2', 3'-dideoxy- 2', 3'-difluoro-5-methyluridine (13), ita arabino analogue 19, arabino-5-methylcytosine analogue 21, 3'-deoxy-2', 3'-didehydro-2'-fluorothymidine (25), Y-azido-2', 3'-dideoxy-2'- fluoro-5-methyluridine (29), 2'-azido-3'-fluoro-2', 3'-dideoxy-5-methyluridine (31), and 2', 3' ...

Ethanoic anhydride Structure

Ethanoic anhydride

[(2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl methanesulfonate Structure

[(2R,3S,5R)-3-f...

~58%

[(2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl acetate Structure

[(2R,3S,5R)-3-f...

2,3'-ANHYDRO-1-(2'-DEOXY-5'-O-METHYLSULFONYL-β-D-THREO-PENTOFURANOSYL)-THYMINE Structure

2,3'-ANHYDRO-1-...

~%

[(2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl acetate Structure

[(2R,3S,5R)-3-f...

1-[(2R,3S,4R,5R)-3,4-difluoro-5-(trityloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3S,4R,5R...

~48%

1-[(2R,3S,4R,5R)-3,4-difluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3S,4R,5R...

Triphenylmethyl Chloride Structure

Triphenylmethyl...

Methanesulfonyl chloride Structure

Methanesulfonyl...

5-Methyluridine Structure

5-Methyluridine

~%

[(2R,3R,4R,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-methylsulfonyloxy-2-(trityloxymethyl)oxolan-3-yl] methanesulfonate Structure

[(2R,3R,4R,5R)-...

5-methyl-1-[(2R,4R)-4-(trityloxymethyl)-3,6-dioxabicyclo[3.1.0]hexan-2-yl]pyrimidine-2,4-dione Structure

5-methyl-1-[(2R...

~%

1-[(2R,3S,4R,5R)-3,4-difluoro-5-(trityloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3S,4R,5R...

Anhydro nucleoside Structure

Anhydro nucleoside

~43%

[(2R,3R,4R,5R)-3,4-difluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl benzoate Structure

[(2R,3R,4R,5R)-...

Benzoyl chloride Structure

Benzoyl chloride

~%

[(2R,3R,4R,5R)-3,4-difluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl benzoate Structure

[(2R,3R,4R,5R)-...

2'-Fluoro-5-methylarabinosyluracil Structure

2'-Fluoro-5-met...

~%

[(2R,3R,4R,5R)-3,4-difluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl benzoate Structure

[(2R,3R,4R,5R)-...

Methanesulfonic acid Structure

Methanesulfonic acid

2,3'-ANHYDRO-1-(2'-DEOXY-5'-O-METHYLSULFONYL-β-D-THREO-PENTOFURANOSYL)-THYMINE Structure

2,3'-ANHYDRO-1-...

~50%

3',5'-di-o-mesylthymidine Structure

3',5'-di-o-mesy...

1-[(2R,3S,4S,5S)-4-azido-3-hydroxy-5-(trityloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3S,4S,5S...

~%

1-[(2R,3R,4R,5S)-4-azido-3-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3R,4R,5S...

5-methyl-1-[(2R,4R)-4-(trityloxymethyl)-3,6-dioxabicyclo[3.1.0]hexan-2-yl]pyrimidine-2,4-dione Structure

5-methyl-1-[(2R...

~%

1-[(2R,3R,4R,5S)-4-azido-3-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3R,4R,5S...

[(2R,3R,4R,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-methylsulfonyloxy-2-(trityloxymethyl)oxolan-3-yl] methanesulfonate Structure

[(2R,3R,4R,5R)-...

~%

1-[(2R,3R,4R,5S)-4-azido-3-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3R,4R,5S...

5-Methyluridine Structure

5-Methyluridine

~%

1-[(2R,3R,4R,5S)-4-azido-3-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3R,4R,5S...

Benzoyl chloride Structure

Benzoyl chloride

~%

Anhydro nucleoside Structure

Anhydro nucleoside

2'-Fluoro-5-methylarabinosyluracil Structure

2'-Fluoro-5-met...

~%

Anhydro nucleoside Structure

Anhydro nucleoside

5-methyl-1-[(2R,4R)-4-(trityloxymethyl)-3,6-dioxabicyclo[3.1.0]hexan-2-yl]pyrimidine-2,4-dione Structure

5-methyl-1-[(2R...

~20%

1-[(2R,3R,4R,5R)-3-azido-4-hydroxy-5-(trityloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3R,4R,5R...

1-[(2R,3S,4S,5S)-4-azido-3-hydroxy-5-(trityloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3S,4S,5S...

Triphenylmethyl Chloride Structure

Triphenylmethyl...

~%

1-[(2R,3R,4R,5R)-3-azido-4-hydroxy-5-(trityloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3R,4R,5R...

[(2R,3R,4R,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-methylsulfonyloxy-2-(trityloxymethyl)oxolan-3-yl] methanesulfonate Structure

[(2R,3R,4R,5R)-...

~%

1-[(2R,3R,4R,5R)-3-azido-4-hydroxy-5-(trityloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3R,4R,5R...

5-Methyluridine Structure

5-Methyluridine

~%

1-[(2R,3R,4R,5R)-3-azido-4-hydroxy-5-(trityloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3R,4R,5R...

1-[(2R,3S,4S,5R)-3-azido-4-fluoro-5-(trityloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3S,4S,5R...

~60%

1-[(2R,3S,4S,5R)-3-azido-4-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3S,4S,5R...

5-methyl-1-[(2R,4R)-4-(trityloxymethyl)-3,6-dioxabicyclo[3.1.0]hexan-2-yl]pyrimidine-2,4-dione Structure

5-methyl-1-[(2R...

~%

1-[(2R,3S,4S,5R)-3-azido-4-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3S,4S,5R...

1-[(2R,3R,4R,5R)-3-azido-4-hydroxy-5-(trityloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3R,4R,5R...

~%

1-[(2R,3S,4S,5R)-3-azido-4-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3S,4S,5R...

[(2R,3R,4R,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-methylsulfonyloxy-2-(trityloxymethyl)oxolan-3-yl] methanesulfonate Structure

[(2R,3R,4R,5R)-...

~%

1-[(2R,3S,4S,5R)-3-azido-4-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3S,4S,5R...

5-Methyluridine Structure

5-Methyluridine

~%

1-[(2R,3S,4S,5R)-3-azido-4-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Structure

1-[(2R,3S,4S,5R...

An efficient synthesis of 3′-fluoro-3′-deoxythymidene (FLT)

[Hager, Michael W.; Liotta, Dennis C. Tetrahedron Letters, 1992 , vol. 33, # 47 p. 7083 - 7086]