Alditols dideoxy

Intramolecular cyclization can also be effected with acyclic intermediates derived from such readily available alditols as D-mannitol. Kuszmann and Vargha63 reported the formation of 2,5-anhydro-l,6-dibromo-l,6-dideoxy-4-0-(methylsulfonyl)-D-glucitol (63), in 73% yield, by boiling 3,5-di-0-acetyl-l,6-dibromo-l,6-dideoxy-2,4-di-0-... 

In addition to these physical studies at the Bureau, Tipson was able to return to his synthetic interests, both alone and in collaboration with other staff members. He was especially pleased to prepare D-talose in crystalline form, an accomplishment that had eluded Emil Fischer. Pursuing his longstanding interest in the reaction of sulfonic esters with iodide and following an earlier observation that the tetratosyl ester of erythritol is converted into butadiene by the action of sodium iodide and zinc, he demonstrated (with A. Cohen) that nonterminal unsaturation may be conveniently introduced into alditol derivatives by reaction of contiguous secondary sulfonates with sodium iodide and zinc dust in boiling A.A-dimethylformamide. This Tipson-Cohen reaction subsequently proved of great utility in other hands for the conversion of more complex carbohydrate structures into vicinal dideoxy derivatives. 

Among them are found the naturally occurring 1-deoxynojirimycin (DNJ) and 1-deoxymannojirimycin (DMJ) [96]. Practical syntheses of DNJ and DMJ start from L-gulono-1,4-lactone (20b) and o-mannono-1,4-lactone (74), respectively [97]. Key intermediates are 2,6-dibromo-2,6-dideoxy-D-alditol derivatives 75a and 75b obtained by 2,6-dibromination of the starting lactones, followed by reduction with NaBH4 [98, 99]. Then a five-step sequence involving selective partial protection, introduction of an amine functionality, and intramolecular N-alkylation, lead to DNJ and DMJ, respectively (Scheme 22). 

Many bacterial polysaccharides have been analyzed as alditol acetates,15-16,18,53,420-431-447 and, for those that contain 3,6-dideoxy sugars,... 

Unless otherwise noted, acetone was the solvent. 6 Yield of monodeoxy-monoiodo-alditol derivative. Yield of dideoxy-diiodo-alditol derivative. d Yield of sodium sulfonate. Free iodine liberated. i Acetonylacetone. Plus sodium bicarbonate to prevent cleavage of the benzylidene group. Acetic anhydride. 

Lithium chloride, preferably dissolved in absolute ethanol, has also been used306 419 420 for preparing alkyl chlorides. Dissolved in absolute ethanol-acetone (1 1, by vol.), it has recently414 found application with alditol sulfonates. Its action on l,4 3,6-dianhydro-2,5-di-0-mesyl-L-iditol, l,4 3,6-dianhydro-2,5-di-0-mesyl-D-mannitol, and l,4 3,6-dian-hydro-2,5-di-0-mesyl- (and -2,5-di-O-tosyl-) sorbitol resembles the action of sodium iodide on these compounds, i.e., the first displays no appreciable reaction, the second gives the 2,5-dichloro-2,5-dideoxy derivative, and the last two afford the respective monochloromonodeoxy-mono-O-sulfonyl derivatives. Treatment of l,4 3,6-dianhydro-2,5-di-0-mesyl-sorbitol during 48 hours at 180-90° gives some of a dianhydro-mono-chloromonodeoxy-sorbitoleen. 

This product was identical with abequose, and its reduction with sodium borohydride gave an alditol identical with abequitol. This alditol had a rotation equal and opposite to that of cohtitol their infrared spectra were indistinguishable. Colititolis, thus, 3,6-dideoxy-L-a 2/lo-hexitol. 

Attempts to use 4,5,7-tri-0-acetyl-2,6-anhydro-l,3-dideoxy-l-iodo-D-giuco-heptitol for x-ray analysis were unsuccessful, because only twinned crystals could be prepared. Use of die deacetylated p-toluenesulfonate, namely, 2,6-anhydro-3-deoxy-l-0-p-tolylsulfonyl-D-gl co-heptitol, and of the parent alditol, 2,6-anhydro-3-deoxy-D-glaco-hepti-tol, was unsuccessful because no atom of sufficient electron density was present. 

SCHEME 13.15 Chemoenzymatic synthesis of l,5-dideoxy-l,5-imino-alditols. 

The Sharpless asymmetric aminohydroxylation [552] of the electron-deficient 2-vinylfuran 469 gives a 7 1 mixture of semi-protected amino-alcohols 470 and 471 (41%). The major product 472 (ee > 86%) was reduced by diisobutylaluminum hydride giving a diol [553] which is then converted into the /3-hydroxyfurylamine derivative 473, an important synthetic building block for various biologically important compounds, including l,5-dideoxy-l,5-imino-alditols such as 474 (O Scheme 110). A less regioselective, but shorter way to intermediate 473 is the direct asymmetric aminohydroxylation of vinylfuran [554,555]. 

Two examples of desulfurization reactions of sugar dithioacetals, in which episulfonium ion formation is postulated, are pertinent here. Treatment of the 3-amino-3,6-dideoxy-D-mannose derivative (324) with Raney nickel gave some of the 1,2,6-trideoxy alditol (326), along with the... 

Alditol derivatives containing non-terminal double bonds have also been reported. Treatment of 1,2 5,6-di-0-isopropylidene-3,4-di-O-p-tolylsul-fonyl-D-mannitol with sodium benzoate in iV,A -dimethylformamide afforded, in addition to saturated products of displacement, 3-deoxy-1,2 5,6-di-0-isopropylidene-4-0-p-tolylsulfonyl-D-(/ireo-hex-3-enitol and the corresponding tetrol formed by hydrolysis of the acetal rings. 1,2 5,6-Di-O-isopropylidene-D-mannitol and -D-altritol have been converted into the trans and cis isomers, respectively, of 1,2 5,6-di-O-isopropylidene-3,4-dideoxy-D-(/irco-hex-3-enitol by the thionocarbonate method. ... 

When D-fl/ ahmo-hexulose phenylosazone (216) was reduced over Raney nickel in 2M alcoholic potassium hydroxide (added to open the chelated ring), the reduction proceeded to the alditol stage and yielded 1,2-diamino-1,2-dideoxy-D-mannilol and -D-glucitol (217 and 218).249,411,412 Similar reductions have been carried out on disaccharide phenylosazones244,393,394,413 and dehydroascorbic acid osazone (Scheme 50).414,415... 

The component in peak A gave a mass spectrum identical with that of the alditol acetate of a 3,6-dideoxy-2,4-di-0-methyIhexose. As tyvelose is the only 3,6-dideoxy-hexose present, the component of the first peak must be the corresponding alditol acetate, methylated at 0-2 and 0-4. The component in peak B gave a mass spectrum characteristic of a mixture of the alditol acetates from a 6-deoxy-2,3-di-0-methylhexose (27) and a 2,3,4,6-tetra-O-methylhexose (28). 

Additional examples of this methodology include the synthesis of 1,1-difluoro-l-iodo alditols 583 [627], 2-azido-l,2-dideoxy-l-iodo-alditols 585 [628,629] and chiral vinyl sulfones 587 [630] by fragmentation of carbohydrate anomeric alkoxy radicals generated from the respective carbohydrates 582, 584 and 586 (Scheme 3.231). 

Acid-catalysed hydrolysis, followed by hydrogenation of the known methyl 4-azido-4,6-dideoxy-2,3-0-isopropylidene-a-L-mannopyranoside gave the 1,4-imino alditol 26, which had L-rhamnosidase inhibitory activity. The corresponding lactam was also made but was devoid of glycosidase activity. ... 

A rapid route to N-substituted trihydroxypiperidines (l,5-dideoxy-l,5-imino-pentitols) by nucleophilic opening of bis-epoxides derived from d- and L-ara-binitol, D-xylitol and related compounds has been reported. The 3-0-benzyl-Zn s-epoxides, generated by tosylation of the primary hydroxyl groups followed by treatment with sodium hydride and benzyl bromide, were treated with primary amines to yield piperidine/pyrrolidine mixtures, whose composition was found to be dependent on the nature of the alditol precursor, the amine and the reaction... 

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