Hakomori reaction, methylation

The modified Hakomori reaction consists of dissolving approximately 1 mg of sample in 100 1 of a 1M solution of NaH in dimethyl sulfoxide. Approximately 35 /rl of methyl iodide is added, the reaction vessel is capped and agitated for 60-75 s, and reaction is immediately quenched by addition of 250 /il of water and 250 il of chloroform. The chloroform layer is removed, washed repeatedly with water and evaporated to yield the permethyl derivative. 

Methylatiott. Hakomori reported that glycosides of polysaccharides can bt rapidly permethylated by treatment with dimsylsodium in DMSO followed by reaction with methyl iodide ... 

The most important development in methylation technique is due to Hakomori, who used as the base methylsulfinyl carbanion, formed by reaction of methyl sulfoxide with sodium hydride, and thus extended to carbohydrates the reaction developed by Corey and Chaykovsky/ In certain cases, completely methylated polysaccharide may be obtained in high yield by one treatment within an hour. This method was used by Sandford and Conrad in a re-examination of the polysaccharide from Aerobacter aerogenes, and their paper should be consulted for the excellent experimental details contained therein. These authors showed that this polysaccharide has a simple, repeating structure, and previous suggestions that it is complicated and highly branched arose from interpretation based on products of incomplete methylation. 

NRRL B-742 dextran may be artifactual structures, resulting from incomplete methylation of this highly branched polysaccharide. Dextrans have been methylated most frequently by the Haworth method, " and by procedures that employ sodium and methyl iodide in liquid ammonia. " " Rapid methylation of dextrans has been achieved " through the use of the Hakomori procedure, which utilizes methyl sulfoxide as solvent for the dextran. Careful control of the reaction temperature would, however, appear to be essential when a dextran is methylated in this solvent, as hot methyl sulfoxide has been reported to depolymerize native dextrans." ... 

The Hakomori method has also been used extensively in the methylation of carbohydrates however, yields were typically low and non-sugar products were observed. Subsequent studies by Ciucanu and Kerek [40] led to the conclusion that OH and H were more effective bases than the methylsulfinyl carbanion. These authors developed a new method for the permethylation of carbohydrates using CH3I and solid NaOH in DMSO. This reaction is relatively clean, proceeds to completion in about 6-7 min, and gives very high yields ( 98%). The derivatization may also be performed with KOH, NaH (excess) and sodium t-butoxide. Ciucanu and Kerek have extensively reviewed the experimental parameters and have published a table of procedures, reagents, reaction times and yeilds for various other versions of Ihe permethylation reaction [40]. 

Substitution reactions at secondary hydroxyls are generally performed either for analysis of structure or to serve a protective function during other reactions. Etherification of the nonanomeric hydroxyls was an important structural tool in the analysis of oligosaccharide and polysaccharide structure. Methyl ethers have been employed for structural determination for more than 75 years. Thus, methyl ether formation in a polysaccharide results in substitution only at free hydroxyls. Subsequent analysis of the methylated derivatives reveals positions previously occupied in glycosidic linkage. Reagents used for this purpose have evolved from dimethylsulfate to the commonly employed method of Hakomori using sodium hydride and dimethylsulfoxide. 

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