2-Deoxythymidine, structure

The first drug to be approved for clinical use was AZT, a structural analog of deoxythymidine. AZT was first synthesized in 1964 by Jerome P. Horwitz. It failed as an anticancer drug (the purpose for which it was made), but in 1985 it was found to be a useful treatment for AIDS. AZT is taken up by T lymphocytes, immune system cells that are particularly vulnerable... 

Write the structures of (a) deoxythymidine and (b) ribothymidine (occurs as a minor constituent in some forms of RNA). 

A similar approach started with (45)-(2 )-5-acetoxy-4-formyloxy-2-pentenal (11) or the de-formylated (4S)-(2 )-5-acetoxy-4-hydroxy-2-pentenal (12), which were prepared from tri-O-acetyl-D-glucal55. Both aldehydes added hydrazoic acid to afford, after acidic cyclization and alkylation, an almost 1 1 mixture of the 3-azido-2,3-dideoxypentoses 13 in 79% total yield from 12 and 31 % total yield from 11. The structures of the products are confirmed by their NMR spectra and by further conversion to 3 -azido-3 -deoxythymidine (AZT) and its stereoisomers, the absolute configurations of which are known. 

The use of fluoroarene derivatives as structural mimetics of nucleobases has been studied extensively [47, 48]. In pioneering work in this field, Kool and co-workers reported the structural similarity between natural 2 -deoxythymidine (dT) and l, 2 -dideoxy-l -(2,4-difluoro-5-methylphenyl)- 3-D-ribofuranoside 92 (dF) (see Figure 10.9) [49, 50]. 

The primary structure of DNA is the way in which the DNA building blocks are linked together. Whereas proteins have over twenty building blocks to choose from, DNA has only four—the nucleosides deoxyadenosine, deoxyguanosine, deoxycytidine, and deoxythymidine (Fig. 6.1). 

Solid-state NMR has been used extensively for characterizing the structures of N-desmethylnefopam HC1 (38), patellin (39), erythromycin A dihydrate (40), and the amorphous nature of ursodeoxycholic acid (41). The conformations of 3 -amino-3 -deoxythymidine (42), gramicidin A (43), and amiodarone HC1 (44) have been confirmed by solid-state NMR. 

Comparison ot the structures of the normal nucleoside, 2 -deoxythymidine, and the nucleoside analog, 3 -azido-2, 3 -dideoxjdhymidine. 

The X-ray crystal structure of an oligonucleotide containing four 4 -thio-2 -deoxythymidine nucleotides has been solved. The modification confers nuclease resistance to oligodeoxynucleotides. 

An exceptional case of an acylphosphonate in which nucleophiles react at the phosphorus rather than at the carbonyl is that of the mixed anhydride of pivalic acid and pivaloylphosphonyl monoester of 5 0-DMT-2 -deoxythymidine (equation 54). In this compound the keto function is especially unreactive, because of steric hindrance, while the phosphorus is unusually electrophilic, being both a mixed anhydride and an acylphos-phonyl function at the same time. As a consequence of these structural features, this compound reacts at the phosphorus with nucleophiles, such as water, ethanol or pyridine, to give products resulting from P—O bond cleavage (equation 54). 

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