Chlorodeoxy

The potential utility of this method in the synthesis of chlorodeoxy sugars cannot be fully appraised at the present time owing to the lack of sufficient examples. 

The Preparation of Chlorodeoxy Sugars by Reaction with Sulfuryl Chloride... 

An attractive feature in this reaction is the possibility of direct substitution and formation of unblocked sugar derivatives containing one or more chlorodeoxy function in essentially two steps. Another facet is the formation of methyl 4,6-dichloro-4,6-dideoxy-hexosides from certain methyl glycosides in one step. Such compounds could be valuable intermediates in the synthesis of dideoxy and diamino sugars of biological importance. 

For 49, the reaction was highly successful in that a 3-O-formate ester (127) was indeed formed in a reaction period of 1 to 2 hours at room temperature with 121 followed by usual processing. Refluxing the solution for 3 to 4 hours afforded a chlorodeoxy sugar in 69-71% yield which proved to be 120 rather than the expected 3-chloro derivative (d-alio). 

It would be reasonable to expect that the decomposition of the N,N-dimethylimino ester chlorides proceeds via a bimolecular mechanism already demonstrated for the thermal decomposition of simple imino ester salts (79). In the carbohydrate series, where an isolated secondary hydroxyl group is involved, such a process would result in chlorodeoxy sugar derivatives with overall inversion of configuration, provided that the approach of the chloride ion is not sterically hindered. Further experiments are in progress in this laboratory utilizing additional model substance to establish the scope and stereochemical course of the chlorination reaction. 

Chlorodeoxy sugars by thermal decomposition of O-imino ester chlorides, synthesis of. .. 192 N-( 2-Chloro-l,l,2-trifluoroethyl) -... 

The relationship between structure and enhancement of sweetness in chlorodeoxysucroses was studied by Hough and Khan. Examination of a range of mono-, di-, tri-, and tetra-chlorodeoxy derivatives of sucrose and galacto-sucTOse suggested that C-4, C-1, and C-6 appear to be important in the enhancement of sweetness when substituted with chloro substituents. The increase in sweetness is substantial if a combination of two of these hydroxyl groups is replaced for example, the 4,l -dichloride (55) and the r,6 -dichloride (56) were reported to be respectively 120 and 76 times... 

Hirota Y, Yoshioka A, Tanaka S, et al. Imbalance of deoxyribonucleoside triphosphates, DNA doublestrand breaks and cell death caused by 2-chlorodeoxy adenosine in mouse FM3 A cells. Cancer Res 1989 49 915-919. 

J. K. N. Jones and his colleagues have extensively studied the reaction of sulfuryl chloride with carbohydrates.21-29 This work has elucidated the stereochemical principles involved in the various transformations, and has made available a convenient and effective procedure for the preparation of chlorodeoxy sugars. Several examples of the utility of such derivatives, obtained by way of a reaction with sulfuryl chloride, in the synthesis of other rare sugars are discussed in Section III (see p. 281). In the present Section, the studies on the reaction itself are surveyed. 

Deoxyhalogeno sugars are susceptible to nucleophilic attack, leading either to displacement, elimination, or anhydro-ring formation. The ease of displacement decreases in the order I > Br> Cl > F the iodo and bromo derivatives have, therefore, been especially utilized in such reactions, although several reactions with chlorodeoxy sugars have now been reported as a result of the increased availability of these compounds. The approach delineated in Section 11,1 (see p. 227) for predicting the reactivity of sulfonic esters can be expected also to be applicable, in an approximate and qualitative way,... 

An investigation of the reduction of chlorodeoxy sugars with lithium aluminum hydride has been reported.68 In one experiment, 3-deuterio-l,2 5,6-di-0-isopropylidene-a-D-allofuranose (197) was prepared, and converted into 3-chloro-3-deoxy-3-deuterio- l,2 5,6-di-0-isopropyl-idene-a-D-glucofuranose (198) by treatment with triphenylphos-phine-carbon tetrachloride reduction with lithium aluminum hydride gave 3-deoxy-3-deuterio-1,2 5,6-di-O-isopropylidene-a-D-r/foo-hexofuranose (199), a result which established that the reduction must have occurred with, retention of configuration at C-3. 

A major part of this chapter is concerned with a discussion of a method for the synthesis of chlorodeoxy sugars by direct replacement of hydroxyl groups by chlorim... 

In Section 11.8 a discussion of the reaction of sulfuryl chloride with carbohydrate derivatives is presented, and in Section III are given some experimental procedures representative of this method for the synthesis of chlorodeoxy sugars and procedures of simple processes for the conversion of the chlorodeoxy sugars into other rare sugars. 

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