SYNTHESES OF PYRROLO[2,3-D]PYRIMIDINE 2',3'-DIDEOXYRIBONUCLEOSIDES RELATED TO 2',3'-DIDEOXYADENOSINE AND 2',3'-DIDEOXYGUANOSINE AND INHIBITORY ACTIVITY OF 5'-TRIPHOSPHATES ON HIV-1 REVERSE-TRANSCRIPTASE

Autor(en): SEELA, F
MUTH, HP
ROLING, A
Stichwörter: 2',3'-DIDEOXYNUCLEOSIDES; 2'-DEOXYRIBOFURANOSIDES; 3'-AZIDO-3'-DEOXYTHYMIDINE; ANALOGS; Chemistry; Chemistry, Multidisciplinary; DEOXYGENATION; LIQUID; NUCLEOSIDES; PHASE-TRANSFER GLYCOSYLATION; TRIPHOSPHATE; TUBERCIDIN
Erscheinungsdatum: 1991
Herausgeber: NEW SWISS CHEMICAL SOC
Journal: HELVETICA CHIMICA ACTA
Volumen: 74
Ausgabe: 3
Startseite: 554
Seitenende: 564
Zusammenfassung: 
The synthesis of 4-chloropyrrolo[2,3-d]pyrimidine and 2-amino-4-chloropyrrolo[2,3-d]pyrimidine alpha-D- and beta-D-2',3'-dideoxyribonucleosides 6a, b and 7a, b is described (Scheme 1). Glycosylation of the pyrrolo[2,3-d]-pyrimidinyl anions of 1a, b with in situ prepared 2,3-dideoxy-alpha/beta-D-glycero-pentofuranosyl chloride (2) was regioselective but afforded anomeric mixtures of the 2',3'-dideoxyribonucleosides 3a/4a and 3b/4b, respectively. The glycosylation products were deprotected and subjected to nucleophilic displacement yielding various pyrrolo[2,3-d]pyrimidine 2'3'-deoxyribonucleosides related to 2',3'-dideoxyadenosine and 2',3'-dideoxyguanosine. One-pot phosphorylation gave the corresponding triphosphates. Some of them are strong inhibitors of HIV-1 reverse transcriptase, similar to corresponding purine 2',3'-dideoxynucleotides, but exhibit a better selectivity index in comparison to DNA polymerases. According to that, the N(7) of the purine moiety is not an essential binding position of ddATP or ddGTP at the active centre of HIV-1 reverse transcriptase.
ISSN: 0018019X
DOI: 10.1002/hlca.19910740312

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