5′-Benzoyl-2′α-bromo-3′-O-methanesulfonylthymidine: A superior nucleoside for the synthesis of the anti-AIDS drug D4T (Stavudine)

Chen, Bang‐Chi; Quinlan, S. L.; Stark, Derron R.; Reid, Joyce A.; Audia, Vicki H.; George, J. G.; Eisenreich, Emerich; Brundidge, S. P.; Racha, Saibaba; Spector, Richard H.

doi:10.1016/0040-4039(95)01752-4

Cited by 25 publications

(7 citation statements)

References 20 publications

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“…The ARVs stavudine (d4T) and zidovudine (AZT) can both be prepared from 5-methyluridine (5-MU) (Chen et al, 1995a(Chen et al, ,b,1998Shiragami et al, 1996). Preparation of 5-methyluridine and derivatives by chemical routes, for example from silylated thymine and protected 1-O-acetylribofuranosides, suffers from several disadvantages.…”

Section: Introductionmentioning

confidence: 99%

Defining a process operating window for the synthesis of 5-methyluridine by transglycosylation of guanosine and thymine

Gordon

Visser

Brady

et al. 2011

Journal of Biotechnology

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Section: Introductionmentioning

confidence: 99%

Defining a process operating window for the synthesis of 5-methyluridine by transglycosylation of guanosine and thymine

Gordon

Visser

Brady

et al. 2011

Journal of Biotechnology

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“…For synthesis of the left-hand nucleoside partner, advantage was taken of the elegant Bristol-Myers Squibb process for converting 5-methyluridine into d4T23 based on seminal work by Fox involving uridine 24. This methodology could be carried out efficiently on a several-grm-scale with a single clean-up chromatography step at the end and was superior to other methodologies25 such as that using acetyl bromide 26.…”

Section: Chemistrymentioning

confidence: 99%

[d4U]-Spacer-[HI-236] double-drug inhibitors of HIV-1 reverse-transcriptase

Younis

Hunter

Muhanji

et al. 2010

Bioorganic & Medicinal Chemistry

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Four double-drug HIV NRTI / NNRTI inhibitors 15a-d of the type [d4U]-spacer- in which the spacer is varied as 1-butynyl (15a), propargyl-1-PEG (15b), propargyl-2-PEG (15c) and propargyl-4-PEG (15d) have been synthesized and biologically evaluated as RT inhibitors against HIV-1. The key step in their synthesis involved a Sonogashira coupling of 5-iodo d4U's benzoate with an alkynylated tethered HI-236 precursor followed by introduction of the HI-236 thiourea functionality. Biological evaluation in both cell-culture (MT-2 cells) as well as using an in vitro RT assay revealed 15a-c to be all more active than d4T. However, overall the results indicate the derivatives are acting as chain-extended NNRTIs in which for 15b-d the nucleoside component is likely situated outside of the pocket but with no evidence for any synergistic double binding between the NRTI and NNRTI sites. This is attributed, in part, to the lack of phosphorylation of the nucleoside component of the double drug as a result of kinase recognition failure, which is not improved upon with the phosphoramidate of 15d incorporating a 4-PEG spacer.

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“…Another development to circumvent the problem of glycosidic bond cleavage during the reduction step with zinc was reported by Chen et al using a sulfonyl group in the 3'position of 5-methyluridine (15) instead of an acetyl group [96,97]. Starting from 5-methyluridine (15) the cis bromosulfonate 32 was obtained in three steps.…”

Section: Synthesis Of 2'3'-didehydro-2'3'-dideoxynucleosidesmentioning

confidence: 99%

Synthesis of 2,3-Didehydro-2,3-dideoxynucleosides via Nucleoside Route.

Len¹,

Postel²

2006

COS

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2',3'-Didehydro-and 2',3'-dideoxynucleosides are both potent antiviral agents. In particular, they are Nucleoside Reverse Transcriptase Inhibitors and hence active against HIV, the ethiological agent of AIDS. They are also intermediates for the synthesis of antiviral 2',3'-dideoxynucleosides. Various aspects of synthetic routes to 2',3'-unsaturated nucleosides are reviewed with examples being chosen from work published between 1966 and 2003.

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5′-Benzoyl-2′α-bromo-3′-O-methanesulfonylthymidine: A superior nucleoside for the synthesis of the anti-AIDS drug D4T (Stavudine)

Cited by 25 publications

References 20 publications

Defining a process operating window for the synthesis of 5-methyluridine by transglycosylation of guanosine and thymine

Defining a process operating window for the synthesis of 5-methyluridine by transglycosylation of guanosine and thymine

[d4U]-Spacer-[HI-236] double-drug inhibitors of HIV-1 reverse-transcriptase

Synthesis of 2,3-Didehydro-2,3-dideoxynucleosides via Nucleoside Route.

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