𝔖 Bobbio Scriptorium
✦   LIBER   ✦

3′-Substituted and 2′,3′-Unsaturated 7-Deazaguanine 2′,3′-Dideoxynucleosides: Syntheses and Inhibition of HIV-1 Reverse Transcriptase

✍ Scribed by Frank Seela; Heinz-Peter Muth

Publisher
John Wiley and Sons
Year
1991
Tongue
German
Weight
659 KB
Volume
74
Category
Article
ISSN
0018-019X

No coin nor oath required. For personal study only.

✦ Synopsis

The syntheses of 2',3'-dideoxy-2',3'-didehydro-~-o-ribofuranoside 1 and 2',3'-dideoxy-3'-fluoro-p-~-ribofuranoside 5 of 7-deazaguanine as well as 7-deaza-2'-deoxyxyloguanosine (3) are described. The corresponding 2,4-diamino compounds 2 and 4 were also prepared. Thus, silylation of 2-amino-4-chloro-7-(2-deoxy-~-~-erythropentofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine (6) afforded 7, which gave the 0x0-nucleoside 13 after oxidation with 00,. NaBH, reduction yielded 14 which, upon deprotection (Bu,NF) and nucleophilic displacement, afforded 3 and 4. On the other hand, the N2-formyl derivative of 7 was mesylated (+ lo), treated with Bu,NF, and deprotected with NH, yielding the 2',3'-dideoxy-2',3'-didehydro-nucleoside 12. Nucleophilic displacement reactions on 12 yielded 1 and 2. The fluoro-nucleoside 5 was obtained from 14 after methoxytritylation of the NH, group (-+ 16), fluorination with DAST (+ 17), and treatment with 2M NaOH. The 5'-triphosphates of 5 and other pyrrolo[2,3-d]pyrimidine 2',3'-dideoxy-3'-fluoro-nucleosides were found to be highly active inhibitors of HIV-1 reverse transcriptase, similar to those of 1 and 2.

Purine and pyrimidine 2',3'-dideoxyribonucleosides including those with a double bond between C(2') and C(3') or carrying an F-substituent at C(3'), with 3',4'-erythroconfiguration, show antiviral activity, in particular against retro viruses such as HIV-1 [l]. The activity is reduced, if the 3'-substituent is in thveo-configuration [2]. On the other 2 3

📜 SIMILAR VOLUMES

1,7-Dideaza-2′,3′-dideoxyadenosine: Synt
1,7-Dideaza-2′,3′-dideoxyadenosine: Syntheses of Pyrrolo[2,3-b]pyndine 2′,3′-Dideoxyribofuranosides and Participation of Purine N(1) during HIV-1 Reverse Transcriptase Inhibition
✍ Frank Seela; Rainer Gumbiowski 📂 Article 📅 1991 🏛 John Wiley and Sons 🌐 German ⚖ 720 KB

## Abstract The syntheses of 1,7‐dideaza‐2′,3′‐dideoxyadenosine (1) and related pyrrolo[2,3‐__b__]pyridine 2′,3′‐dideoxyribi and 2′,3′‐didehydro‐2′,3′‐dideoxyribonucleosides (see 2–5) are described. As starting materials, 2′‐deoxyribo‐nucleosides 6 or 7 were used. The 3′‐OH group was removed by __B

Syntheses of Pyrrolo[2,3-d]pyrimidine 2′
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
✍ Frank Seela; Heinz-Peter Muth; Angelika Röling 📂 Article 📅 1991 🏛 John Wiley and Sons 🌐 German ⚖ 720 KB

## ~~~~~ ~ ~ ~ The synthesis of 4-chloropyrrolo[2,3-d]pyrimidine and 2-amino-4-chloropyrrolo[2,3-d]pyrimidine a -D-and ~-~-2',3'-dideoxyribonucleosides 6a, b and 7a, b is described (Scheme 1). Glycosylation of the pyrrolo[2,3-d]pyrimidinyl anions of la, b with in situ prepared 2,3-dideoxy-a /B-D-g

Syntheses and Reactions of 1′,2′-Unsatur
Syntheses and Reactions of 1′,2′-Unsaturated 2′,3′-Seconucleoside Analogues
✍ Valerije Vrček; Vesna Čaplar 📂 Article 📅 1995 🏛 John Wiley and Sons 🌐 German ⚖ 612 KB

The 1',2'-unsaturated 2',3'-secoadenosine and 2',3'-secouridine analogues were synthesized by the regioselective elimination of the corresponding 2',3'-ditosylates, 2 and 18, respectively, under basic conditions. The observed regioselectivity may be explained by the higher acidity and, hence, prefer

New syntheses of 7-substituted-2-aminoth
New syntheses of 7-substituted-2-aminothieno- and furo[3,2-d]pyrimidines
✍ Philip E. Morris Jr.; Arthur J. Elliott; John A. Montgomery 📂 Article 📅 1999 🏛 Journal of Heterocyclic Chemistry 🌐 English ⚖ 406 KB

## Abstract In a recent publication, we have the described the synthesis of 7‐substituted‐2‐amino‐1,5‐dihydro‐4__H__‐pyrrolo[3,2‐__d__]pyrimidin‐4‐ones which are potent inhibitors of the enzyme Purine Nucleoside Phosphorylase from the corresponding 3‐aminopyrroIe‐2‐carboxylate esters. A key step in