Optical activity sugars

The formulas in Sections II-VI usually represent, for simplicity, molecules belonging to the D configurational series, although they actually refer to racemic mixtures. Section VII deals with the preparation of optically active sugars in this Section, the formulas indicate the true configuration of the molecules. 

For the synthesis of optically active sugars, a number of natural compounds has been successfully employed. The rather obvious prerequisite of such syntheses is the retention of configuration of chiral centers during all operations that are involved in conversion of the substrate into the desired sugar. Some readily available, natural products as, for the example, tartaric and amino acids have particularly often been used for that purpose. 

Stereospeclflc reactions leading to optically active sugar derivatives. The cadmium salt of the 2-allyloxybenzimidazole derivative reacts with various aldehydes to afford adduct in high regio- and stereoselectivity. Adducts lb are subsequently transformed into trans-vinyloxirane 17... 

The formulas of racemic products in this chapter are shown in the D form for reasons of simplicity. When optically active sugars are obtained, their formulas reflect their real configuration. 

In recent years the discovery of novel methods of asymmetric synthesis has greatly increased the ability of organic chemists to synthesize optically active sugars. For example, the asymmetric epoxidation reaction discovered by Katsuki and Sharpless [142] was recently used as the key step in a synthesis of D-oleandrose 118 from divinyl carbinol 119 by Hatakeyama et al. [143]. An alternative approach to asymmetric synthesis of oleandrose was taken by Danishefsky et al. [144,32] in their synthesis of avermectin which is the first, and currently the only, reported total synthesis of an avermectin. The key step of this synthesis was a cyclocondensation reaction of optically active diene 121 with acetaldehyde catalyzed by the optically active Lewis acid (-h)-Eu(hfc)3 [145]. The resulting chiral pyrone was then elaborated to methyl-L-oleandroside 113. This was further converted to the disaccharide glycal 122 by a 4 step sequence in which glycoside formation was accomplished by iV-iodosuccinimide mediated addition of the alcohol to a glycal followed by tributyltin hydride... 

Cyclodextrins exhibit chiral recognition characteristics, because the cavities inside are formed from optically active sugars. Cyclodextrins have been introduced as ligands in NPLC as early as 1989 for the separation of sugar alcohols and various saccharides [35]. Risley and Strege [36] used such a stationary phase for the separation of polar chiral compounds, which could not be resolved under nonaqueous NP conditions. 

Some idea of the very wide range of molecules which have been coupled to proteins can be gained from a few examples. In some instances the protein-coupled complexes have interesting clinical and pharmacolo cal properties. The variable or R portion of all these complexes has in neral been attached to the para position in the diazonium salt, though in specific instances ortho and meta positions have been used. The R may be simple aliphatic or aromatic acids, ethers, alcohols, etc. (1), cationic or anionic radicals (335), or they may be such substances as morphine or strychnine (336), amino acids (337), polypeptides (338), cholesterol (339), androstanediol (340),histamine (341,342),adrenalin (343),aspirin (344), quinine (345), thyroxine (346), optically active sugars (347), and even type-specific pol3r8aeeharides of some of the pneumococci capsules (348). 

Isolates from Indian tobacco Q obelia inflata L.), as a cmde mixture of bases, have been recognized as expectorants. The same (or similar) fractions were also used both in the treatment of asthma and as emetics. The principal alkaloid in T. inflata is lobeline (49), an optically active tertiary amine which, unusual among alkaloids, is reported to readily undergo mutarotation, a process normally associated with sugars. Interestingly, it appears that the aryl-bearing side chains in (49) are derived from phenylalanine (25, R = H) (40). 

Polarimetric determination of the sucrose concentration of a solution is vaUd when sucrose is the only optically active constituent of the sample. In practice, sugar solutions are almost never pure, but contain other optically active substances, most notably the products of sucrose inversion, fmctose and glucose, and sometimes also the microbial polysaccharide dextran, which is dextrorotatory. Corrections can be made for the presence of impurities, such as invert, moisture, and ash. The advantage of polarization is that it is rapid, easy, and very reproducible, having a precision of 0.001°. 

In the second method, which can be applied to compounds with an optically active center near the potentially tautomeric portion of the molecule, the effect of the isomerization on the optical activity is measured. In favorable cases both the rate of racemization and the equilibrium position can be determined. This method has been used extensively to study the isomerization of sugars and their derivatives (cf. reference 75). It has not been used much to study heteroaromatic compounds, although the very fact that certain compounds have been obtained optically active determines their tautomeric form. For example, oxazol-5-ones have thus been shown to exist in the CH form (see Volume 2, Section II,D,1, of article IV by Katritzky and Lagowski). 

Extensive work has been done by using buta-l,3-dienyl-glycosides of unprotected sugar to study aqueous Diels-Alder reactions and to prepare optically active oligosaccharides [20]. 

As 29 had been recognized as the most accessible starting-material for the synthesis of racemic carba-sugars, its resolution was successfully achieved with optically active a-methylbenzylamine as chiral reagent. Reaction of 29 with (-l-)-a-methylbenzylamine gave a mixture of two diastereoisomeric salts [(+)-amine, (—)-29 and (+)-amine, (-l-)-29], which were well separated, and the former salt was converted into (—)-29, [a] -111.8° (ethanol). Analogously, (+)-29, [a] +110.7° (ethanol), was obtained. ... 

All sixteen of the racemic carba-sugars predicted are known, as well as fifteen of the enantiomers. The most accessible starting-material for the synthesis of racemic carba-sugars is the Diels-Alder adduct of furan and acrylic acid, namely, e i o7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylicacid (29). Furthermore, adduct 29 is readily resolved into the antipodes, (—)-29 and (+)-29, by use of optically active a-methylbenzylamine as the resolution agent. The antipodes were used for the synthesis of enantiomeric carba-sugars by reactions analogous to those adopted in the preparation of the racemates. 

Among other carba-sugar derivatives, the most important compounds are amino carba-sugars having an amino group at C-1. They are known as validamine, valiolamine, hydroxyvalidamine, and valienamine, and are found in validamycin antibiotics as unique components they have been synthesized in dl forms and also in optically active forms. 

The presence of asymmetric carbon atoms also confers optical activity on the compound. When a beam of plane-polarized hght is passed through a solution of an optical isomer, it will be rotated either to the right, dextrorotatory (+) or to the left, levorotatory (—). The direction of rotation is independent of the stereochemistry of the sugar, so it may be designated d(—), d(+), l(—), or l(+). For example, the naturally occurring form of fructose is the d(—) isomer. 

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