An efficient stereoselective total synthesis of 3'-azido-3'-deoxythymidine (AZT) and 3'-azido-2',3'-dideoxyuridine (AZDDU, CS-87) from readily available and inexpensive starting material, D-mannitol has been achieved.
3'-Azido-3'-deoxythymidine (AZT) has been found to be a potent antiviral agent against human immunodeficiency virus type 1 (HIV-l) in vitro l-5 and found to decrease the mortality -and opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS)6.
Currently, AZT is the only chemotherapeutic agent available for AIDS patients. 3'-Aaido-2',3'-dideoxyuridine (AZDDU, CS-87) has also been found to be a potent antiviral agent against HIV-l in vitro7'8 and is presently undergoing preclinical toxicology.
AZT was originally synthesized from thymidine by Horwita and his coworkers'. AZDDU (CS-87) has also been synthesized from 2'-deoxyuridine by a similar approach""'. Short supplies of AZT, due to the high demand for the drug as well as the expensive starting material (thymidine and 2'-deoxyuridine) required for the synthesis of both AZT and AZDDU prompts us to develop an efficient general method for these compounds.
Recently, total synthesis of AZT by the condensation of thymine with a preformed 3azido-2-deoxyribofuranose derivative has been reported 12,13