Cyclitols conformation

The application of conformational analysis9 has been of considerable value in understanding some reactions of cyclitols it will, therefore, be... 

At first glance inositol appears to be a relatively simple molecule - on closer examination, a host of sophisticated stereochemical issues, chiral, prochiral, and conformational reveal themselves (Parthasarathy and Eisenberg, 1986, 1990 Postemak, 1965). In fact, the complexity of stereochemical issues in cyclitols, namely cyclohexanes with one hydroxyl group on three or more ring atoms, is well recognized (IUPAC, 1976 Postemak, 1965) inositol can serve as a good model for a sophisticated discussion of various forms of isomerism. 

The Pd-catalyzed carbocyclization affects good control on the orientation of the newly formed OH group [192] (O Scheme 49). Thus, 225 and 227 afford the corresponding cyclitols with almost complete selectivity. In the rearrangement of 227, the stereoselectivity is controlled by the bulky silyl ether-protecting group, which effects the conformational change. 

P2i/c Z = 4 Dx = 1795 R = 0.045 for 1,680 intensities. The molecule has a chair conformation, with the ester group axially attached, and ring torsion-angles of 55 to 60°. The orientation of the phosphate group is asymmetric with respect to the m symmetry of the cyclitol moiety, with a C-1-C-2-0-2-P torsion angle of —124°. 

The cyclopentane cyclitols have been characterized by nuclear magnetic resonance. The conformational analysis of cyclopentene and of poly-substituted cyclopentanes has been discussed. 

For many cyclitols, a convenient, short-cut version of the Whiffen-Brewster calculations may be used, namely (1) consider the most stable chair conformation of the molecule, for which purpose, Dreiding stereomodels are helpful (2) then assume that each ee or ea —CHOH—CHOH— grouping contributes -t-45 if it is in the front-left conformation (149), and —45° if it is in the front-right conformation (143). Each diaxial —CHOH—CHOH— grouping, and each isolated asymmetric center, makes a contribution of zero. The sum of the numbers is then equal to the molecular rotation predicted (for water and the d line of sodium). 

Less ambiguous results have been obtained by examination of the electrophoretic behavior of cyclitols. With these, the possibility of complex-formation with open-chain and with five-membered ring structures, as in the case of aldoses and ketoses, does not arise. The complex-forming compounds of this group all possess a m-m-1,2,3-triol system. Their rates of migration have been related to the instability factors of their conformations possessing this triol system as in (13). 

The first such approach to the interpretation of optical rotation in terms of the conformational properties of carbohydrates was made by Whifien in 1956. He proposed that the observed rotation of an optically active molecule can be regarded as an algebraic summation of partial rotatory contributions of various conformational elements of asymmetry. For these contributions, empirical values were determined that allowed estimation of the net rotations of various cyclic sugars and cyclitols with fair accuracy. A more extensive treatment was presented by Brewster,and it was applied to a wide range of optically active, acyclic and cyclic compounds. The best correlations between the calculated and the experimental values were obtained with compounds that do not absorb in the near-ultraviolet and have predictable, fixed conformations, or for which the conformational populations can be reliably estimated. In the carbohydrate field, the calculations are quite simple for the poly-hydroxycyclohexanes, - and differences between the calculated and observed values for the rotation have been interpreted in terms of conformational equilibria. Similar comparisons have been made for the methyl D-aldopyranosides, although the lack of precision in the correlation does not allow a detailed treatment in terms of conformational populations. 

A number of branched chain nitro-cyclitols have been prepared by Michael addition of lithium dithiane to unsaturated nitrosugars followed by cyclization (Scheme 4) conformational effects in the 6-nitro-a/de/iydo-sugar on the stereo-... 

The good yields obtained in the cyclization of appropriate radical precursors show that this is a convenient method for the synthesis of branched-chain cyclitols from carbohydrates. In addition, an interesting stereoelectronic effect in the cyclization of these acychc sugar derivatives is demonstrated the stabilizing effect of electron-attracting groups vicinal to carbon-centered radicals determines the preferred conformation in the transition state and the stereochemical outcome of the reaction. 

Figure 13.8 Cyclitol epoxides and aziridine may feature ideal conformational behavior for retaining p-exoglucosidases inhibition.

Photoconversion of 118 into cyclitols 119 and 120 has been observed.However only product 119 is formed when 118 is treated with 3-dehydroquinate synthase prompting the question does the enzyme catalyse 118 to 119 or just provide a conformational tmplate to prevent formation of 120 ... 

Cyclitols do not form alkylidene derivatives with the same ease as acyclic carbohydrates. However, the technique of Dangschat and Fischer, wherein zinc chloride catalysis is used, enables the formation of isopropylidene derivatives. They made brilliant use of this reaction in their elucidation of the structures of shikimic acid, quinic acid, conduritol, and mj/o-inositol (see above). The structures of the naturally occurring methyl ethers, pinitol and quebrachitol, were determined with the aid of this reaction (7, ISa, b), L-Inositol and cpi-inositol can be converted to triisopropylidene derivatives (7). This requires acetonation of trans hydroxyl groups. A chair conformation of the ring does allow vicinal trans hydroxyl groups in the equatorial plane to approach one another closely (7). 

Studies on the conformational and stereochemical aspects of the Ferrier reaction leading to cyclitols and azido cyclitols as an extension of earlier work (Vol. 19, p. 173) have been reported. The synthesis of racemic 6-acetamido-l,2-anhydro-6-deoxy-ffiyo-inositol as a tight binding inhibitor and pseudosubstrate for A/ -acetyl-p-D-glucosaminidase has appeared starting from racemic tetra-O-acetylconduritol. ... 

The cyclitol derivatives (27) and (28) (see Chapter 18) were found to adopt in solution the "inverted" conformations shown, with the benzyloxymethyl groups axially disposed. ... 

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