Nucleosides 5 -deoxy-4 -fluoro-5 -iodo-, preparation

D-lyxopyranosyl nucleosides with hydrogen halides to give the 3 -bromo- or 3 -chloro-3 -deoxy-nucleosides (406), or a mixture of the 2 - and 3 -fluoro-deoxy-nucleosides (407). 9-(3-Deoxy-3-iodo-)3-D-xylofuranosyl)hypoxanthine has been synthesized and converted into 3 -amino-3 -deoxy- and 3, 4 -unsatu-rated nucleosides as shown in Scheme 138. Both l-(2-deoxy-2-fluoro- and 2-chloro-2-deoxy-j8-D-arabinofuranosyl)cytidine have been prepared from the corresponding halogeno-sugar derivatives by standard methods (see Schemes 43 and 46). ... 

Many 5-alkyl-, 5-alkenyl-, and 5-alkynyl-l-(2-deoxy-2-fluoro- 5-D-arabin-ofuranosyl)pyrimidines (750 - 752 and 765 - 767) were prepared - " by condensation of 742 (or the equivalent, such as 743) with C-5-substituted pyrimidine derivatives, or by attachment of a C-fragment to C-5 of the existing nucleosides through their 5-iodo or 5-chloromercuri derivatives, or by further conversion of the attached C-5 substituent into another one. ... 

The synthesis of a series of 2 -fluoro-5-substituted arabinofuran-osyl-cytosines and -uracils has been described. 5-Methyluracil and 5-iodocytosine derivatives were the most effective against herpes simplex virus. The arabino configuration was essential for antibiotic activity, and corresponding chloro and bromo analogues were less effective.5 -Bromo-, 5 -fluoro-, and 5 -iodo-deriv-atives of 5-fluorouracil have been prepared conventionally. The a-anomer of 5 -fluoro-5 -deoxyuridine has been synthesized from a 1,2-oxazoline derivative of 5-deoxy-5-fluoro-D-ribose, in turn prepared by a sulphonate displacement using pyridinium fluoride. Treatment of 1-(o-D-arabinofuranosyl)-uracil with diphenylcarbonate yielded the 1,4-oxazin derivative (23) which yielded the 2 -chloro-2 -deoxy-arabino-a-nucleoside (24) on chlorination this was then reduced to the 2 -deoxy analogue (25). 5-Fluorouridine has been... 

The anticancer nucleoside Gemcitabine as its monophosphate derivative (3) has been modified by conjugation of squalene at the N4-position. Using a combination of cryo-EM and SAXS it was shown that the squalenoyl derivative exists as a unilamellar liposome, and that the nanoassembly exhibited enhanced activity compared with Gemcitabine in a resistant cell line." Various C6-modified 2 -deoxy-2 -fluoro-dUMP derivatives have been prepared as potential inhibitors of orotidine 5 -monophosphate decarboxylase (ODCase) of these, the most potent analogue was the 6-iodo-derivative which was found to covalently inhibit ODCase. Aminoacyl-tRNAs... 

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