A new Synthesis of 1-(2,3-Dideoxy-β-D-Glycero-Pent-2-Enofuranosyl)- Thymine. A Highly Potent and Selective Anti-Hiv Agent
- 1 February 1990
- journal article
- research article
- Published by Taylor & Francis in Nucleosides, Nucleotides and Nucleic Acids
- Vol. 9 (2) , 245-258
- https://doi.org/10.1080/07328319008045136
Abstract
A high yielding, straightforward synthesis of 1-(2,3-dideoxy-β-D-glyceropent-2-enofuranosyl)thymine (d4T) (10) is reported through a simple oxidation step of key intermediates such as, 1-(5-O-pivaloyl-3-deoxy-3(R)-phenylseleno-β-D-glyceropentofuranosyl)thymine (7) [1 → 3 → 5 → 7 → 9 → 10], or 1-(5-O-(4-methoxytrityl)-3-deoxy-3(R)-phenylseleno-β-D-glycero pentofuranosyl)thymine (6) [1 → 2 → 4 → 6 → 8 → 10]. The scope of this synthesis is also demonstrated by a simple preparation of a potential prodrug of d4T, 1-(2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-5-methylcytosine (d4C5me) (15), both from 1-(5-O-MMTr-2,3-dideoxy- β-D-glyceropent-2-enofuranosyl)thymine (8), and 1-(5-O-pivaloyl-2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)thymine (9)., Furthermore, 3′, 5′-dideoxy-3′, 5′-bis(phenylselenyl)thymidine (19) produced only 2-methylene-5-(R)-(thymin-1-yl)-2,5-dihydrofuran (22) through an oxidation followed by mild alkali treatment.This publication has 20 references indexed in Scilit:
- General syntheses of 2',3'-dideoxynucleosides and 2',3'-didehydro-2',3'-dideoxynucleosidesThe Journal of Organic Chemistry, 1989
- The 2′,3′-dideoxyriboside of 2,6-diaminopurine selectively inhibits human immunodeficiency virus (HIV) replication invitroBiochemical and Biophysical Research Communications, 1987
- Synthesis and antiviral activity of various 3'-azido, 3'-amino, 2',3'-unsaturated, and 2',3'-dideoxy analogs of pyrimidine deoxyribonucleosides against retrovirusesJournal of Medicinal Chemistry, 1987
- A Convergent Regiospecific Synthesis of the Lariat-Trinucleotides and A2′p 5′Gand A2′p 5′G3′p 5′Cfrom A O4-2-Nitrophenyl) -Uridine Building BlockNucleosides and Nucleotides, 1987
- Both 2′,3′-dideoxythymidine and its 2′,3′-unsaturated derivative (2′,3′-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitroBiochemical and Biophysical Research Communications, 1987
- Chemotherapeutic approaches to the treatment of the acquired immune deficiency syndrome (AIDS)Journal of Medicinal Chemistry, 1986
- Synthesis of O2'-Methyluridine, O2'-Methylcytidine, N4,O2'-Dimethylcytidine and N4,N4,O2'-Trimethylcytidine from a Common Intermediate.Acta Chemica Scandinavica, 1986
- Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS)Science, 1983
- Halo sugar nucleosides. IV. Synthesis of some 4',5'-unsaturated pyrimidine nucleosidesThe Journal of Organic Chemistry, 1974
- Pyrimidine nucleoside transformations via anhydronucleosidePublished by Walter de Gruyter GmbH ,1969