Ribose 2-deoxy-2-fluoro-, derivatives

Oligonucleotides containing 2 -deoxy-2 -fluoro-D-arabinose or -D-ribose form stable, triple-heUcal complexes stabilized by the intermolecular 2 -OH phosphate contacts and sugar puckering these derivatives have promoted interest in relation to compounds synthesized for DNA targeting in vivo Fig. 6 [31]. 

Modified Oligonucleotides with Ability to Activate RNase H. Uniformly 2 -modified oligonucleotides are not capable of activating RNase H in an oligonucleotide/RNA hybrid. However, recent reports show that hybrids of RNA and arabinonucleic acids [the 2 -stereoisomer of RNA based on o-arabinose instead of the natural o-ribose (2 -arabino-OH, ANA) and 2 -deoxy-2 -fluoro-D-arabinonucleic acid (2 F-ANA)] are substrates of RNase H (358,359) (Fig. 5.9). However, ANA/RNA hybrids had a lower value, compared to that of the control DNA/RNA hybrids. This destabilization (AT, = -1.0°C/modification) is presumed to derive from steric interference by the -C2 -OH group, which is oriented into the... 

L-Xylose has been converted into a 2-deoxy-2-fluoro-P-L-arabinofuranose derivative, by way of a fluoride ion displacement of an imidazolylsulfonate, and then into a range of pyrimidine nucleosides. Displacement of another imidazolylsulfonate with Et3N.3HF initially formed the corresponding sulfonyl fluoride which was subsequently displaced by fluoride ion. Methyl 2,3-dideoxy-3-fluoro-5-0-(4-methylbenzoyl)-a-D-ribofuranoside, an intermediate for the syntheses of some anti-HIV nucleosides, has been synthesized from 2-deoxy-D-ribose in five steps and in 24% yield. ... 

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... 

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