Deoxy derivatives halogens

In contrast to uridine,389 cytidine does not yield a 5 -chloro-5 -deoxy derivative on reaction with N,N-dimethyl(chlorometh-animinium) chloride instead 2,2 -anhydrocytidine is formed.395 However, thionyl chloride or bromide in hexamethylphosphor-amide at room temperature achieves this selective replacement of the primary hydroxyl group of halogen in cytidine, and also in adenosine, in respective yields of 80 and 75% for the chloro compounds, and 55 and 30% for the bromo analogs.396... 

Other stable diazoalkanes, such as diazoketones, can also be converted into halogen derivatives, as illustrated by the conversion of 3,4-di-O-benzoyl-l-deoxy-l-diazo-D-g/t/cero-tetrulose into the 1-bromo- and 1-chloro-deoxy derivatives by the action of hydrogen bromide and hydrogen chloride, respectively.196... 

Deoxysugars, nucleosides and related molecules have also been prepared from hydroxy-protected, halogenated precursors using tributyltin hydride 55,58,. Thus in one example, the key step of the preparation of a 3 -deoxy derivative of S-formycinyl-L-homocysteine was the reduction of a halide precursor (equation 7)62. 

From study of the action of invertase on derivatives of sucrose and methyl jS-D-fructofuranoside, it was concluded that small changes at positions 1, or 6 cause loss of enzymic acitivity various azido-, deoxy, and halogenated-derivatives were examined. " ... 

The reaction is quite susceptible to steric effects since hindered secondary hydroxyl groups were found to be unreactive. The method can therefore be used to selectively replace a primary hydroxyl group by halogen in the presence of more hindered secondary hydroxyl groups in the same molecule. An example (70) is the reaction of 52 with triphenylphosphite methiodide which affords the 6-deoxy-6-iodo derivative 53 (60%) in which the C-2 hydroxyl group remains intact. 

Regioselective deacylation has also been observed189 in the acid-catalyzed transesterification of some 3, 5 -di-0-acetyl-2 -deoxy-2 -halo-uridines in methanol to give the corresponding 3 -0-acetyl derivatives in yields of 36-66%. The presence of the 2-halogen substituent seems essential for the selectivity in the case of 2, 3, 5 -tri-0-acetyl-uridine, no significant differences in the reaction rates of the acetyl groups towards transesterification were apparent. 

Halogen atoms have been placed at C-6 of substituted 6-deoxy-hexoses by a variety of interesting ways, and the products provide potential routes to 6-deoxyhexoses. Helferich and coworkers 4 reported a low yield of methyl 6-chloro-6-deoxy-a-D-glucoside which they prepared by reaction of the (suitably protected) corresponding 6-trityl ether with phosphorus pentachloride. Sinclair 44 has provided a convenient procedure for the preparation of the 6-chloro derivative in yields of 30-35% by allowing methyl a-D-glucopyranoside to react with sulfur monochloride, SjClj, in N,/V-dimethylformamide. A much better yield (73%) of the 6-bromo derivative was reported1 in the reaction of methyl 2,3,4-tri-O-benzoyl-6-O-trityl-a-D-altroside with phosphorus tribromide and bromine. 

A reaction, that does not involve the enediol takes place on halogenation. Treatment of 138 with hydrogen bromide-acetic acid affords 5-0-acetyl-6-bromo-6-deoxy-L-ascorbic acid (166).360 Compound 166 was used for the synthesis of 6-substituted derivatives of 138, via the 5,6-anhydro derivative.361... 

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