2 ,3 -didehydro-3 -deoxythymidine

Separation of 2, 3 -didehydro-3 -deoxythymidine 5 -(methoxyalaninyl phosphate) triethylammonium salt... 

Yajima, T., Juni, K., Saneyoshi, M., et al. Direct transport of 2, 3 -didehydro-3 -deoxythymidine (D4T) and its ester derivatives to the cerebrospinal fluid via the nasal mucous membrane in rats. Biol. Pharm. Bull. 21 272-277, 1998. 

In general, thermodynamically stable trans olefins are formed, while cis olefins are obtained in the case of 1,2-dixanthates derived from cycloalkan-l,2-diols. Here, instead of the Bu3SnH/AIBN system, environmentally benign Ph4Si2H2/AIBN, Ph2SiH2/AIBN, and Af-ethylpiperidine hypophosphite/AIBN systems can also be used. As a typically useful method, preparation of D4T (2/,3/-didehydro-3/-deoxythymidine) analogue, which has the same potent anti-HIV activity as AZT, is shown in eq. 7.16. In practice, D2C (2/,3/-dideoxycytidine) and D4C (2/,3/-didehydro-2/,3/-dideoxycytidine) were also prepared by this method [39, 40]. 

In the past, various serendipitous discoveries have capitalized on the differential expression of enzymes by host and viral infected cells. For example, the prodrug Acyclovir, used widely for the treatment of herpes simplex and herpes zoster infections, is selectively activated through phosphorylation by viral thymidine kinase to acyclovir monophosphate which is then converted to the triphosphate, which inhibits DNA polymerase, by host cellular enzymes. Similarly several 2, 3 -dideoxynucleoside analogs such as Zidovudine (azidothymidine, AZT) and 2, 3 -didehydro-3 -deoxythymidine (D4T) have potent antiviral activity against human immunodeficiency vims (HIV). These compounds are selectively phosphoiylated intracellularly to the 5 -triphosphate derivatives which inhibit the viral reverse transcriptase. 

Reverse Transcriptase - 3 -Azido-2 3 -dideoxythymidine (AZT), when converted to the corresonding 5 triphosphate in cells, is an inhibitor of the HIV reverse transcriptase enzyme, which is responsible for making viral DNA from viral RNA. Other nucleoside analogs, such as 2 3 -dideoxycytidine (ddC), 2 3 -dideoxyinosine (ddl), and 2 3 -didehydro-3 -deoxythymidine (d4T) (see here) are also converted to triphosphates and act by blocking DNA chain elongation after they are incorporated into DNA. 

Several 2, 3 -dideoxynucleosides are given to patients with HIV. These analogs include 3 -azido-2, 3 -dideoxythymidine (zidovudine, AZT), 2, 3 -dideoxycytidine (zalcitabine, ddC), 2, 3 -dideoxyinosine (didanosine, ddl), 2, 3 -didehydro-3 -deoxythymidine (stavudine, d4T), and (-)-2 -deoxy-3 -thiacytidine (lamivudine, 3TC). A related molecule is abacavir (ABC), which contains a cyclopentene-methanol moiety instead of the dideoxyribose moiety of the above-mentioned... 

Didehydro-3 -deoxythymidine, 9CI. l-(2,3-Dideoxy-l3-D-g yceio-pent-2-enofur-anosyl) thymine, SCI. 3 -Deoxy-2, 3 -dide-hydrothymidine. Zerit. D4T. BMY27857 [3056-17-5]... 

Stavudine and its 2, 3 -didehydro-3 -deoxythymidine metabolite were isolated from plasma and urine and analyzed on a Cig column (2 — 266 nm) using a 97/3/1 water (10 mM KH2PO4 to pH 2.5 with H3P04)/acetonitrile/triethylamine mobile phase [1608]. Peaks eluted before 10 min and were well resolved. Standards from 0.025 to 25 pg/mL (plasma) and 2 to 150 pg/mL (urine) were utilized. A limit of detection of 12 ng/mL was reported. 

Elimination. The formation of olefins from the vic-diols via 1,2-dixanthates is very important, especially after the discovery of anti-HIV nuclosides such as D4C (2, 3 -didehydro-2, 3 -dideoxycytidine) and D4T (2, 3 -didehydro-3 -deoxythymidine). Treatment of adenosine 1,2-dixanthates with the TPDS-AIBN method under refluxing conditions in ethyl acetate generates the corresponding 2, 3 -dideoxygenated adenosine nucleoside in quite good yield as shown in eq 7. ... 

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