Configurational analysis, stereochemical

A. Structure, Bonding, and Nomenclature — Lewis structures, orbital hybridization, configuration and stereochemical notation, conformational analysis, systematic IUPAC nomenclature, spectroscopy (IR and 3H and 13 C NMR)... 

The recent development in the stereochemical study of these reactions has already been covered by several reviews (16,17,101-108). The aim of this survey is to provide a general view of the synthesis and configurational analysis of chiral phosphates, and of the significance of stereochemical results in enzyme mechanisms. 

The mechanism of an actual hydrolysis reaction catalyzed by this prototype phosphomonoesterase has never been studied stereochemically. This apparent omission is presumably explained by the very low catalytic efficiency of the enzyme toward phosphorothioate monoesters as compared to phosphate monoesters (75) certainly, chiral [ O, 0]phosphorothioate 0-ester substrates already exist, and methodology is available for the configurational analysis of the chiral [ 0, 0, 0]thiophosphate that would be produced if the chiral substrate were hydrolyzed in H2. In fact, the low catalytic reactivity of phosphorothioate O-esters and the high reactivity of phosphorothioate S-esters has been explained by the enzyme utilizing nucleophilic catalysis (an associate mechanism) to achieve hydrolysis of the phosphate ester bond 40). 

The stereochemical experiment employing the Rp diastereomer of cyclic [ 0, 0]dAMP as substrate was reported in 1981 by Gerlt and co-workers (20). This substrate was also synthesized from a precursor phosphoroanilidate by reaction with C 02. The hydrolysis reaction was performed in H2 0 to generate one of the diastereomers of [ 0, 0, 0]dAMP as product. The configurational analysis of this material was performed with very high stereochemical integrity by first using adenylate kinase, pyruvate kinase, a trace of ATP, and... 

Matsumori, N., Kanono, D., Murata, M., Nakamura, H., and Tachibana, K. (1999). Stereochemical determination of acyclic structures based on carbon-proton spin-coupling constants. A method of configuration analysis for natural products. J. Org. Chem. 64, 866-876. 

Of particular interest is calycinine, which possesses a meta substitution pattern in ring D, and fuseine, which is the first simple lactam known in the aporphine series. A complete X-ray analysis was carried out on the 7V,0-diacetyl derivative of 4-hydroxynornantenine to confirm its stereochemistry and absolute configuration. " The stereochemical assignments for all 4-hydroxylated apor-phines are, therefore, predicated upon this X-ray study. 

It has been indicated by Rusakov et al that the experimental Vnse couplings measured for sterically crowded phenylselanylalkenes can be applied in configurational analysis of these compounds only in combination with detailed theoretical calculations. As follows from the analysis performed by the authors, the typical Karplus dependence of Juse be strongly afiected by the orientation of the terminal substituent bearing selenium atom. Another paper has been devoted by these authors to stereochemical behaviour of Vnse > HSe couplings in five pyrazolyl-1,-3-diselenanes and 1,2-diselenolane. 

Infrared and Raman spectroscopy (considered together) Molecular identification determination of chemical functionality chain and sequence length quantitative analysis stereochemical configuration chain conformation. (d,e)... 

Potter, B. V. L., Connolly, B. A, and Eckstein, F. (1983) Synthesis and configurational analysis of a dinucleoside phosphate isotopically chiral at phosphorus Stereochemical course of penicillium citrum nuclease PI reaction Biochemistry 1369-1377. 

To illustrate the application and configurational analysis of chiral [> 0, 0, 0]thiophosphate, we describe the stereochemical study of 5 -nu-... 

By such a P-NMR analysis, Webb and Trentham have also elucidated the stereochemical course of a number of nucleoside triphosphatases (Webb, 1982). The P-NMR analysis based on the combined effects of and 0 is the only method available for configurational analysis of chiral [ 0, 0, 0]Psi, and is also a commonly used method for configurational analysis of chiral [ 0, 0, 0]phosphomonoesters, which are covered by Gerlt (Chapter 7.)... 

Rather than providing a comprehensive description of all the stereochemical studies that have utilized P-NMR methods of configurational analysis, three examples that demonstrate the techniques described in Section III are given. These are chosen from the studies carried out in the author s laboratory. 

Stereochemical analysis can add detail to the mechanistic picture of the Sj l substitution reaction. The ionization mechanism results in foimation of a caibocation intermediate which is planar because of its hybridization. If the caibocation is sufficiently long-lived under the reaction conditions to diffirse away from the leaving group, it becomes symmetrically solvated and gives racemic product. If this condition is not met, the solvation is dissymmetric, and product with net retention or inversion of configuration may be obtained, even though an achiral caibocation is formed. The extent of inversion or retention depends upon the details of the system. Examples of this effect will be discussed in later sections of the chapter. 

Stabilization of a carbocation intermediate by benzylic conjugation, as in the 1-phenylethyl system shown in entry 8, leads to substitution with diminished stereosped-ficity. A thorough analysis of stereochemical, kinetic, and isotope effect data on solvolysis reactions of 1-phenylethyl chloride has been carried out. The system has been analyzed in terms of the fate of the intimate ion-pair and solvent-separated ion-pair intermediates. From this analysis, it has been estimated that for every 100 molecules of 1-phenylethyl chloride that undergo ionization to an intimate ion pair (in trifluoroethanol), 80 return to starting material of retained configuration, 7 return to inverted starting material, and 13 go on to the solvent-separated ion pair. 

Compounds of types i, 2, and 3 were deduced to have planar, trigonal configurations from kinetic and stereochemical observations71 however, confirmation of this postulate was provided only a few years ago by the X-ray structure analysis of (bistrimethylsilyl)aminobis(trimethylsilylimino)phosphorane8). The P/N(imine) bonds were found to be relatively short, which was attributed to a high rc-bonding component in the planar system of coordinatively unsaturated phosphorus. 

---