SYNTHESIS OF A SERIES OF PURINE 2',3'-DIDEOXY-L-NUCLEOSIDE ANALOGUES AS POTENTIAL ANTIVIRAL AGENTS

Abstract Various 2′,3′-dideoxy-L-nucleoside analogues, 6-amino-9-(2,3-dideoxy-β-L-ribofuranosyl) purine (19), 2-chloro-6-amino-9-(2,3-dideoxy-β-L-ribofuranosyl)-purine (20), 2-chloro-6-amino-9-(2,3-dideoxy-4-thio-β-L-ribofuranosyl) purine (21), 2,6-diamino-9-(2,3-dideoxy-β-L-ribofuranosyl) purine (26), 2,6-diamino-9-(2,3-dideoxy-β-thio-β-L-ribofuranosyl)-purine (27), 2-amino-6-chloro-9-(2,3-dideoxy-β-L-ribofuranosyl) purine (28), 6-chloro-9-(2,3-dideoxy-4-thio-β-L-ribofuranosyl) purine (29), and 6-amino-9-(2,3-dideoxy-4-thio-β-L-ribofuran-osyl) purine (30) have been synthesized by coupling of the sodium salt of 2-amino-6-chloropurine (1), 6-chloropurine (2), and 2,6-dichloropurine (3) with 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (4) or 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-4-thio-L-ribofuranose (5) in anhydrous MeCN in the presence of either EtAlCl2 or Et2AlCl followed by separation of the α/β-anomers and deprotection of the blocking groups. However, the synthesi...

[1]  G. Dutschman,et al.  Studies of the Pharmacokinetics and Toxicology of 2′,3′-Dideoxy-β-L-5-fluorocytidine (β-L-FddC) and 2′,3′-Dideoxy-β-L-cytidine (β-L-ddC) In Vivo; and Synthesis and Antiviral Evaluations of 2′,3′-Dideoxy-β-L-5-azacytidine , 1995 .

[2]  M. Luo,et al.  Synthesis of several pyrimidine l-nucleoside analogues as potential antiviral agents , 1995 .

[3]  G. Koszalka,et al.  Synthesis and biological evaluation of pyrimidine and purine α-L-2',3'-dideoxy nucleosides , 1994 .

[4]  Tai-shun Lin,et al.  Synthesis of 1-β-L-Arabinofuranosylcytosine (β-L-Ara-C) and 2′-Deoxy-2′-methylene-β-L-cytidine (β-L-DMDC) as Potential Antineoplastic Agents , 1994 .

[5]  R. Schinazi,et al.  Pure nucleoside enantiomers of beta-2',3'-dideoxycytidine analogs are selective inhibitors of hepatitis B virus in vitro , 1994, Antimicrobial Agents and Chemotherapy.

[6]  R. Schinazi,et al.  Anti-human immunodeficiency virus activities of the beta-L enantiomer of 2',3'-dideoxycytidine and its 5-fluoro derivative in vitro , 1994, Antimicrobial Agents and Chemotherapy.

[7]  M. Luo,et al.  A stereospecific synthesis of 2',3'-dideoxy-β-L-cytidine (β-L-ddC), a potent inhibitor against human hepatitis B virus (HBV) and human immunodeficiency virus (HIV) , 1994 .

[8]  Y. Cheng,et al.  Synthesis and biological evaluation of 2',3'-dideoxy-L-pyrimidine nucleosides as potential antiviral agents against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). , 1994, Journal of medicinal chemistry.

[9]  G. Dutschman,et al.  Antiviral activity of 2′,3′-dideoxy-β-L-5-fluorocytidine (β-L-FddC) and 2′,3′-dideoxy-β-L-cytidine (β-L-ddC) against hepatitis B virus and human immunodeficiency virus type 1 in vitro , 1994 .

[10]  J. Montgomery,et al.  The Synthesis and Biological Activity of 1-(2-Deoxy-4-Thio-α;-L-Threo-Pentofuranosyl)Thymine , 1993 .

[11]  L W Frick,et al.  The anti-hepatitis B virus activities, cytotoxicities, and anabolic profiles of the (-) and (+) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine , 1992, Antimicrobial Agents and Chemotherapy.

[12]  R F Schinazi,et al.  Selective inhibition of human immunodeficiency viruses by racemates and enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine , 1992, Antimicrobial Agents and Chemotherapy.

[13]  G. Maga,et al.  L-thymidine is phosphorylated by herpes simplex virus type 1 thymidine kinase and inhibits viral growth. , 1992, Journal of medicinal chemistry.

[14]  R. Schinazi,et al.  Deoxycytidine deaminase-resistant stereoisomer is the active form of (+/-)-2',3'-dideoxy-3'-thiacytidine in the inhibition of hepatitis B virus replication. , 1992, The Journal of biological chemistry.

[15]  J. Gerin,et al.  Use of a standardized cell culture assay to assess activities of nucleoside analogs against hepatitis B virus replication. , 1992, Antiviral research.

[16]  R. Schinazi,et al.  Activities of the four optical isomers of 2',3'-dideoxy-3'-thiacytidine (BCH-189) against human immunodeficiency virus type 1 in human lymphocytes , 1992, Antimicrobial Agents and Chemotherapy.

[17]  J. Montgomery,et al.  Synthesis and anti-HIV activity of 4'-thio-2',3'-dideoxynucleosides. , 1992, Journal of medicinal chemistry.

[18]  J. Cameron,et al.  The separated enantiomers of 2'-deoxy-3'-thiacytidine (BCH 189) both inhibit human immunodeficiency virus replication in vitro , 1992, Antimicrobial Agents and Chemotherapy.

[19]  R. Schinazi,et al.  Inhibition of the replication of hepatitis B virus in vitro by 2',3'-dideoxy-3'-thiacytidine and related analogues. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. T. Walker,et al.  The synthesis and antiviral activity of some 4'-thio-2'-deoxy nucleoside analogues. , 1991, Journal of medicinal chemistry.

[21]  M. Wainberg,et al.  Anti-human immunodeficiency virus type 1 activity and in vitro toxicity of 2'-deoxy-3'-thiacytidine (BCH-189), a novel heterocyclic nucleoside analog , 1991, Antimicrobial Agents and Chemotherapy.

[22]  J. Starrett,et al.  Preparation of the geometric isomers of DDC, DDA, D4C and D4T as potential anti-HIV agents , 1991 .

[23]  R. Schinazi,et al.  Synthesis and structure-activity relationships of 6-substituted 2',3'-dideoxypurine nucleosides as potential anti-human immunodeficiency virus agents. , 1990, Journal of medicinal chemistry.

[24]  S. Broder,et al.  Factors determining the activity of 2',3'-dideoxynucleosides in suppressing human immunodeficiency virus in vitro. , 1988, Molecular pharmacology.

[25]  M. Okabe,et al.  Synthesis of the dideoxynucleosides "ddC" and "CNT" from glutamic acid, ribonolactone, and pyrimidine bases , 1988 .

[26]  A. Holý,et al.  Metabolism of pyrimidine L-nucleosides. , 1976, Nucleic acids research.

[27]  U. Niedballa,et al.  Synthesis of nucleosides. 9. General synthesis of N-glycosides. I. Synthesis of pyrimidine nucleosides , 1974 .

[28]  R. Whistler,et al.  Preparation and activity of the 4'-thio derivatives of some 6-substituted purine nucleosides. , 1970, Journal of medicinal chemistry.