L,2:5,6-dianhydro-D-mannitol

Wiggins45 synthesized 1,2,5,6-tetrachloro-tetradesoxy-D-mannitol by an unequivocal route and found it to be identical with the tetrachloro-tetradesoxy-D-mannitol actually obtained from isomannide. Thus isomannide must be l,4 3,6-dianhydro D-mannitol (LI). 

The dimethyl derivative of isomannide was synthesized by Wiggins as follows. l,6-Dichloro-l,6-didesoxy-3,4-isopropylidene-D-mannitol was converted i nto 1,6-dichloro-l, 6-didesoxy-2,5-dimethyl-3,4-isopr opylidene-D-mannitol (LVI). This on mild acid hydrolysis gave 1,6-dichloro-l,6-didesoxy-2,5-dimethyl-D-mannitol (LVII) which with cold sodium methoxide furnished 2,5-dimethyl-l,4 3,6-dianhydro-D-mannitol (LVIII), identical with the product of methylation of isomannide itself. Further... 

Overend, Montgomery and Wiggins60 noted an interesting reaction between isomannide and phosphorus tribromide. None of the expected 2,5-dibromo-2,5-didesoxy-l,4 3,6-dianhydro-D-mannitol (LIX) was isolated instead, ring scission took place and l,6-dibromo-l,6-didesoxy-D-mannitol (LX) was formed. Since no such ring scission occurs with hydrobromic acid under similar conditions it was probable that the phosphorus tribromide itself had effected the ring breakdown by direct attack on the oxide rings. 

The acetates of the l,4 3,6-dianhydrohexitols may also be useful as plasticizers both 2,5-diacetyl-l,4 3,6-dianhydro-D-mannitol and the analogous D-sorbitol derivative have been described.97... 

The hexitol anhydrides also have medicinal uses.97 Carr and Krantz98 found that l,4 3,6-dianhydro-D-mannitol was quite non-toxic to man and was a valuable diuretic. The dinitrates of both isomannide and isosorbide" have possible uses as agents for lowering blood pressure, though Burn and Stephenson100 found that the D-sorbitol derivative was twice as active as the D-mannitol derivative in this respect. 2,5-Diam-ino-2,5-didesoxy-l,4 3,6-dianhydro-D-mannitol and -D-sorbitol have been prepared and their sulfanilamido derivatives obtained.101 These however showed no outstanding bacteriostatic activity. 

The 2,5-diamino-2,5-dideoxy derivatives of l,4 3,6-dianhydro-D-mannitol and -D-glucitol gave, on deamination, the same product, namely, l,4 3,6-dianhydro-L-iditol, in unspecified yield.176 The product presumably arose from carbonium-ion intermediates, which reacted predominantly with solvent on the less hindered, exo sides of the V-shaped molecule. 

Dianhydro-D-fructose (26), a viscous sirup, was obtained during the catalytic oxidation of l,4 3,6-dianhydro-D-mannitol (25) to the corresponding diketone (27). A reaction time of 20 hours at room temper-... 

The direct displacement of secondary sulfonyloxy groups of sugar derivatives by sulfur nucleophiles has received Umited study. Attempted displacement of p-tolylsulfonyloxy groups in methyl 4,6-0-benzylidene-3-O-methyl-2-O-p-tolylsulfonyl-a-D-altropyranoside or 1,2 5,6-di-0-isopro-pylidene-3-O-p-tolylsulfonyl-a-D-glucofuranose, by alkanethiolate anion in an alcohol medium, removed the p-tolylsuKonyl substituent and failed to give any (identifiable) thio sugar product. However, the 2,5-di-methanesulfonate of l,4 3,6-dianhydro-D-mannitol (64) reacted with... 

The acrylate 383, derived from l,4 3,6-dianhydro-D-glucitol, undergoes Diels Alder reactions with cyclopentadiene giving >99% endo products, with a 92% selectivity in favour of the S-endo product 384. The analogous reaction of the l,4 3,6-dianhydro-D-mannitol-derived ester, catalysed by ethylaluminium dichloride, also gives >99% endo products, but with a 90% diastereoselectivity in favour of the R-endo product. 

The 2,5-di-O-sulphonyl esters of l,4 3,6-dianhydro-D-mannitol (11) underwent exchange with sodium iodide to yield a 1 1 mixture of the 2,5-dideoxy-2,5-di-iodo-D-glucitol and o-iditol derivatives (12) and (13) respectively, the 2-deoxy-2-iodo-5-0-methanesulphonyl D-glucitol (14) and o-mannitol (15)... 

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