Iodide 5 -deoxy-5 -

Benzoyl-6-deoxy-6-iodo-2,3-0-isopropylidene-a-i, - xylohexulofura-nose (47). A solution of 15 grams (31.3 mmole) of 46 in butanone (200 ml.) containing dry sodium iodide (9.3 grams, 62 mmole) was refluxed for 24 hours. The reaction mixture was cooled, the sodium tosylate removed by filtration, and the filtrate concentrated to dryness. The residue was partitioned between water (50 ml.) and chloroform (2 X 50 ml.) the combined chloroform solutions were washed with water, dried over sodium sulfate and concentrated to a colorless sirup which spontaneously crystallized. Recrystallization from aqueous methanol afforded pure material in two crops (11.6 grams, 85%), m.p. 115°-117°C, [ ]D24 + 36.0° (c, 5.3). Anal Calcd. for C16H1906 C, 44.2 H, 4.4 I, 29.3. Found C, 44.3 H, 4.5 I, 29.4. 

Perhaps the earliest report of the replacement of a sulfonate ester attached to a secondary carbon atom in a sugar derivative was that of Helferich (53). Under quite drastic conditions (sodium iodide in acetone, 105°C., 72 hours, sealed system) the 4-mesylate derivative 9 was converted into a crystalline 4-deoxy-4-iodo sugar derivative 10 in 46% yield. Although the position of the iodine atom was established, the configuration at C-4 was not known. 

No quantitative data were available on the reactivity at C-4 in hexose sulfonates until the studies of Stevens and co-workers (95). It was shown that when methyl 6-deoxy-2,3-di-0-benzyl-4-0-methylsulfonyl-a-D-gluco-pyranoside (31) was allowed to react with sodium iodide in pentane-... 

Attempted selective displacement (96) of the primary tosylate function in 34 with sodium iodide in refluxing 2-butanone led to the 6-deoxy-6-iodo derivative 35 in 32% yield only, while the di-iodo derivative 36 was formed in 45% yield. These results are to be compared with those reported by Owen and Ragg (85) who observed no reaction with either potassium thiolacetate or potassium thiocyanate in the corresponding / -series. 

The D-gluco analog 37 reacted with sodium iodide in refluxing 2-butanone to give the crystalline 6-deoxy-6-iodo derivative 38 in 82% yield (97). Only 11% of the mixed di-iodo derivative 39 was formed in this case, which reflects on the higher order of reactivity at C-4 in 34 compared to 37. 

In a similar way, 5-O-acetylthymidine was converted into the 3-deoxy-3-iodo derivative 72 in 55% yield. In this case, the replacement of the hydroxyl group by iodine was presumed to have taken place by retention of the configuration at C-3. The first intermediate in the reaction was proposed to be the phosphonate (70) which rapidly collapses to an O-3-cyclonucleoside (71) and the latter is subsequently attacked by iodide ion to give the product 72. It was also observed (106) that treatment of nucleosides containing a cis vicinal diol grouping such as 5-0-acetyluridine with triphenylphosphite methiodide failed to provide iodinated products but gave phosphonate derivatives instead. 

The synthesis of halodeoxy sugars has also been achieved by reaction of sugar phosphorodiamido and phosphonamido derivatives with alkyl halides (83). Heating equimolar amounts of 6-(tetraethylphosphoro-diamido)-l,2 3,4-di-0 isopropylidene-D-galactose with methyl iodide (and benzyl bromide) at 140°C. for 4 hours afforded the 6-deoxy-6-iodo (74b) (75%) and 6-bromo-6-deoxy (74c) (56%) derivatives, respectively. 

Methyl- C]thymine ([ C]FMAU) could be obtained in modest radiochemical yields via cross-coupling of [ CJmethyl iodide with l-(2 -deoxy-2 -fluoro-/3-D-arabinofuranosyl)-5-(trimethylstannyl)uracil. Optimal power was found to be 70W, since an increase to 100 W as well as a decrease to SOW resulted in lower radiochemical yields (Scheme 6). 

As for the synthesis of 5-e/j/-KDG, compound 6 seemed to be a suitable precursor of the methyl ester of 5-deoxy-KDG 20 since only the C-5 hydroxyl was unprotected. In this case the key step was not the epimerization but the removal of that hydroxyl. Our attempts of radicalar deoxygenation of 6 were unsuccessful because the intermediate radical was intramolecularly trappy by the C-2.C-3 double bound. Therefore we first reduced the double bond and then converted the resulting diastereoisomeric alcohols 14 into the corresponding triflates 15 which were submitted to the action of sodium iodide. Finally the iodides 16 Aus obtained were hydrogenolyzed in the presence of diisopropylethylamin to give 17. 

C[ 1h17n o3+ I- h2o 5 -Deoxy-5 -(methylammonium)adenosine iodide, mono- MAADIM10 30 462... 

Complete confirmation of the structures assigned to the ribonucleosides has been provided by a study of their 5-0- p -tolylsulfonyl derivatives. Whereas 2,3-O-isopropylideneuridine and 2,3-O-isopropylideneinosine give 5-p-tolylsulfonyl derivatives which, with sodium iodide, are converted to 5-deoxy-5-iodo compounds,30 31 the corresponding adenosine and cytidine... 

Selective replacement of primary hydroxyl groups in carbohydrates by iodine atoms has been achieved by using the Rydon reagent, namely, methyltriphenoxyphosphonium iodide.368 Treatment of methyl 3,4-O-isopropylidene-jS-D-galactopyranoside with the phosphonium salt in benzene for 48 hours at room temperature yielded 60% of the 6-deoxy-6-iodo derivative,369 and reaction of thymidine, uridine, and 2,2 -anhydrouridine in N,N-dimethylformamide afforded 5 -deoxy-5 -iodo derivatives in yields of 63, 65, and 31%, respectively.370... 

Sn2 reactions of glycosyl iodides have proven especially advantageous in the synthesis of 2-deoxy P-O-aryl-D-glycosides. This is a challenging linkage to make, as there is no neighboring group to participate. Sometimes, stereochemistry is... 

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