Isohexide nitrates

The infrared spectra (benzene solution) of the isohexide nitrates, as well as of their mixed nitric and p-toluenesulfonic esters, are well established. The positions of the v and the bands for the nitrato group are remarkably constant, at 1645 3 cm-1 and 1282 1 -1 (endo), and 1274 1 cm-1... 

For isohexide nitrates gas-liquid chromatographic separation methods using OF-1 (Ref. 52), OV-101 (Refs. 53-59), OV-17 (Ref 60), or OV-210 (Ref 61) columns have been reported. Most of the methods described are used to detect traces of nitrates, as well as of their metabolites, in urine and plasma probes.62-69 All known isohexide nitrates can be measured in mixtures by using a DB-5 capillary column.70-71 Electron-capture detection was applied for the g.l.c. determination of isosorbide dinitrate71 and its metabo-lites.7,b... 

Other methods have also been used for quantitative determination of isohexide nitrates, including colorimetry,73-75 infrared spectroscopy,20 n.m.r. spectroscopy,76 and polarography.47-77-80... 

With this intent, the acetates (R = COCH3, 78a), carbamates (R = CONH2, 78b), sulfamates (R = S02NH2, 78c), and ethyl ethers (R = C2H5,78d) of isosorbide 2- and 5-nitrate were investigated, and found to be similar in activity to the parent compounds.146 Several isohexide nitrates further substituted by purine bases 154 were prepared as potential cardiovascular agents.143... 

An oxidized stage of isohexide nitrates, wherein the remaining hydroxyl group is transformed into the ketone, gives rise to a number of derivatives 161, such as oximes, semicarbazones, acyclic and cyclic acetals, and hydra-zones.154 Among them, 3-amino-2-hydroxypropyl-substituted oxime ethers... 

Isohexide mono- (10-13), as well as di-, nitrates (14-16) show a weak, positive dichroic band at 265 nm (n— D transition) and a second, stronger one near 228 nm, which is positive for endo-R-nitrato and negative for exo-S-nitrato groups. For isosorbide dinitrate (14), both dichroic bands are positive.12,13... 

Four X-ray investigations of isohexide derivatives have been published.39-42 The oldest of them gave very little information about structural details. Two crystallographically independent molecules of 1,4 3,6-dianhydro-2-0-(p-bromophenylsulfonyl)-D-glucitol 5-nitrate (30), having the same conformation, are in the asymmetric unit. 

From among the known isohexides (see Section II), isosorbide (3) is that of the highest importance, not least because of the pharmaceutical use of its nitrates and the good solvent properties of its dimethyl ether. 

Epoxides 72 may also act as starting materials for hybrid structures 77 containing an isohexide and a glyceryl moiety, with nitric ester functions at different positions.172 Additional monoethers of isosorbide 2- and 5-nitrate 78 were synthesized by reaction of the free hydroxyl group with any of several alkyl iodides in the presence of freshly prepared silver oxide. The yields were low, as usual.146 Amongst a larger series of different alcohol... 

Nitroxide radical-forming agents, for example, all seven isohexide mono-and di-nitrates, were claimed as ingredients in topical formulations for stimulation of hair growth.2250... 

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