Synthesis of the dideoxynucleosides "ddC" and "CNT" from glutamic acid, ribonolactone, and pyrimidine bases

Okabe, Masami; Sun, Ruen-Chu; Tam, Steve; Todaro, Louis J.; Coffen, David L.

doi:10.1021/jo00255a021

Cited by 171 publications

(52 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The amorphous residue was purified on a column of SiO 2 (15 g) using first CHCl 3 and then CHCl 3 MeOH (99:1) as eluents. [1,3,4]thiadiazolimino)thymidine (11). From 4a (0.55 g).…”

Section: Methodsmentioning

confidence: 99%

“…Dideoxy-3 -(2,5-dihydro-5,5-dimethyl-[1,3,4]-thiadiazolimino)thymidine (12). [1,3,4]thiadiazolimino)-thymidine (15). -3 -(6,7,8,9-tetrahydro-5H-1,2,4-triazolo [1,5-a]azepin-2-yl)thymidine (27).…”

Section: General Procedures For Preparation Of the Freementioning

confidence: 99%

“…Herdewijin et al [13] and Hirota et al [14] have reported the synthesis of compounds, in which the azide group of AZT is transformed to a triazole ring 3, but these compounds did not show appreciable activity against HIV. Our work here is concerned with the synthesis of new 3 -azole analogues from the cycloaddition of 5 -acetyl-3 -deoxy-3 -isothiocyanatothymidine 9 and 3 -cyano-analogue 19, prepared from the antiviral nucleoside CNT [4,5], with some reactive cumulenes. In our recent work, these cumulenes have been used in the synthesis of new types of 1,2,4-triazole compounds such as C-ribonucleosides [15,16], acyclic C-nucleosides and homo-C-analogues [17], (D-manno-pentitol-1-yl)-anaslogues [18], as well as those 1,2,4-triazoles attached to thymine [19], phthalimide [20], indole [21], quinolone [21], and benzotriazole [22].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis of 3′‐1,2,4‐triazolo‐ and 3′‐1,3,4‐thiadiazoliminothymidines

Al‐Soud

Al‐Masoudi

2003

Heteroatom Chemistry

View full text Add to dashboard Cite

show abstract

“…The amorphous residue was purified on a column of SiO 2 (15 g) using first CHCl 3 and then CHCl 3 MeOH (99:1) as eluents. [1,3,4]thiadiazolimino)thymidine (11). From 4a (0.55 g).…”

Section: Methodsmentioning

confidence: 99%

Section: General Procedures For Preparation Of the Freementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of 3′‐1,2,4‐triazolo‐ and 3′‐1,3,4‐thiadiazoliminothymidines

Al‐Soud

Al‐Masoudi

2003

Heteroatom Chemistry

View full text Add to dashboard Cite

show abstract

“…The natural D-ddNs such as ddC, ddA, and 2Ј,3Ј-dideoxyguanosine (ddG) were first synthesized in the 1960s (25,34,68,73), and various reviews of their syntheses have appeared (23,35). The activities of ddNs with respect to HIV were first realized in 1986 (3, 4, 13, 22, 48-50, 69, 81) (Table 1).…”

Section: Normal D-and L-ddnsmentioning

confidence: 99%

Antiviral activities of isometric dideoxynucleosides of D- and L-related stereochemistry

Nair

Jahnke

1995

Antimicrob Agents Chemother

145

View full text Add to dashboard Cite

In summary, many isomeric analogs of ddNs of both D-related and L-related absolute stereochemistries have been synthesized and evaluated in vitro for their antiviral activities. A few of these compounds exhibit potent antiviral activity and, interestingly, belong to both the D and L families. The synthetic methodologies developed will allow accessibility to many more novel modified nucleosides. While some structure-activity relationships are emerging from this work, it is clear that these chiral isomeric nucleosides have opened a new chapter in the field of antiviral nucleosides.

show abstract

“…Thus, on the one hand, synthetic ,B-L-thymidine has been shown to be selectively phosphorylated by herpes simplex virus type 1 thymidine kinase and to markedly reduce herpes simplex type 1 replication in HeLa cells (41). Although initially reported as having no antiviral activity (24), P-L-2',3'-dideoxycytidine, the mirror image of 2',3'-dideoxycytidine (DDC; or zalcitabine or Hivid), was shown by Mansuri et al (22) (2,5,16,34) enantiomers exhibited more potent anti-HIV activities than the corresponding racemates or D isomers provides a strong rationale for studying the mirror images of other previously described D enantiomers. Among them are L-DDC and 13-L-2',3'-dideoxy-5-fluorocytidine (L-FDDC), since studies of the structure-activity relationship of pyrimidine nucleosides modified at the 5 position indicated that their potencies can be preserved or increased by having this position modified with a halogen.…”

mentioning

confidence: 99%

Anti-human immunodeficiency virus activities of the beta-L enantiomer of 2',3'-dideoxycytidine and its 5-fluoro derivative in vitro

Gosselin

Schinazi

Sommadossi

et al. 1994

Antimicrob Agents Chemother

131

View full text Add to dashboard Cite

The L enantiomer of 2',3'-dideoxycytidine (DDC) was recently shown to inhibit selectively human immunodeficiency virus type 1 (HIV-1) in vitro. In the current study, the potent anti-HIV activity of L-DDC was confirmed and extended to several HIV-1 and HIV-2 strains in various cell culture systems, including primary human lymphocytes and macrophages. Furthermore, its 5-fluoro congener, beta-L-2',3'-dideoxy-5-fluorocytidine (L-FDDC), was found to have more potent anti-HIV activity and a higher therapeutic index in acutely infected human peripheral blood mononuclear cells. These compounds had no marked activity against HIV-1 isolates resistant to the oxathiolane pyrimidine nucleosides (-)-beta-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC] and (-)-beta-L-2',3'-dideoxy-3'-thiacytidine, but 3'-azido-3'-deoxythymidine (AZT)-resistant viruses were susceptible to L-DDC and L-FDDC. Cytotoxicity studies with human myeloid progenitor cells indicated that L-DDC and L-FDDC had median inhibitory concentrations comparable to those of AZT, DDC, and FDDC, but L-DDC and L-FDDC were significantly less toxic than AZT, DDC, and FDDC when erythroid progenitor cells were used. L-FDDC had the highest selectivity indices (6,000 and 9,000 for erythroid and myeloid progenitor cells, respectively) of all the compounds evaluated. Further preclinical development of L-FDDC is warranted in order to determine its potential usefulness in the treatment of HIV infections.

show abstract

Synthesis of the dideoxynucleosides "ddC" and "CNT" from glutamic acid, ribonolactone, and pyrimidine bases

Cited by 171 publications

References 4 publications

Synthesis of 3′‐1,2,4‐triazolo‐ and 3′‐1,3,4‐thiadiazoliminothymidines

Synthesis of 3′‐1,2,4‐triazolo‐ and 3′‐1,3,4‐thiadiazoliminothymidines

Antiviral activities of isometric dideoxynucleosides of D- and L-related stereochemistry

Anti-human immunodeficiency virus activities of the beta-L enantiomer of 2',3'-dideoxycytidine and its 5-fluoro derivative in vitro

Contact Info

Product

Resources

About