Isotope chirality

Phosphate esters, particularly AMP, ADP and ATP, have vital biological functions and this fact has generated intense interest in their reaction mechanisms. Subtle stereochemical experiments, such as the use of isotopically chiral compounds, have been important and, since all biological phosphorylation reactions appear to involve metal ion catalysis, the stereochemistry of phosphate ion coordination has also been subject to much attention.229,230 Apart from its biological significance, this work has revealed some interesting contrasts with the stereochemistry of ligand systems in which saturated carbon units link the donor atoms. 

Asymmetric Autocatalysis Initiated by Isotopically Chiral Primary Alcohols... 

We investigated highly enantioselective asymmetric autocatalysis of a chiral compound induced by the isotopic enantiomer of a primary alcohol-a-d (Scheme 22) [118]. The correlation between the absolute configurations of the obtained pyrimidyl alkanol and the isotopic chiral compound is reproducible, thus the small isotope chirality can be recognized by asymmetric autocatalysis. 

That Robinson s and Ewins compounds did in fact have the trimer structures 1 and 2, respectively, was only established 50 years later by the works of Lindsey [3], Erdtman et al. [4], and Goldup et al. [5], The name cyclotriveratrylene (CTV) was given by Lindsey to 1, which was shown by NMR to adopt the locked crown conformation shown on the stereoformula and later evidenced by X-ray crystallography (Fig. 1) [6, 7], More recently [8], the inversion barrier of the crown in 1 was found to be ca. 26.5 kcal mol 1 from the racemization rate of the isotopically chiral C3-cyclotriveratrylene-d9 (3) relatively uniform values (AG 26.5 to 27.2 kcal/mol) were found [9] for a variety of chiral cyclotriveratrylenes, including the parent compound 4, C3-cyclotribenzylene-d3. Thus, in these compounds, the half-life of a crown conformer in solution is around one month at 20 °C, a few minutes at 100 °C and less than 0.1 second at 200 °C. 

The Baeyer-Villiger reaction occurs with retention of stereochemistry at die migrating center. This stereoselectivity has been utilized in a practical method for the preparation of isotopically chiral metiiyl acetic acid (5) ftom [2- H]cyclohexanone (4) prepared by enzyme-catalyzed stereoselective exchange of the pro-R a -proton and enantioconvergent exchange of the a-proton with deuterium (Scheme 2). As a cautionary note, prior epimerization of an acyl group prior to oxidation has been observed. ... 

Poly(alkyl isocyanate) with isotopic chirality (the uniform chiral field concept) (Green)... 

A sensitive probe applied to understand the nature of the reaction mechanism of group transfer is the stereochemistry of the overall reaction. The reaction at a phosphoryl center normally is a degenerate question, since a monosubstituted phosphate ester or anhydride is proprochiral at the phosphate center. Phosphate centers at a diester or disubstituted anhydride are prochiral. Two related methods to analyze the stereochemistry at a phosphate center have been developed by the generation of chirality at the phosphorus center. The first approach was developed by Usher et al. (24) and gave rise to the formation of isotopi-cally chiral [ 0, 0]thiophosphate esters and anhydrides (I). Isotopically chiral [ 0, 0, 0]phosphates (II) have also been synthesized and the absolute configurations determined. Two primary problems must first be addressed with respect to both of the methods that have been developed the synthesis of the isotopically pure chiral thiophosphates and phosphates and the analysis of the isotopic chirality of the products. An example of the chiral starting substrates, as developed for ATP, is schematically demonstrated. Ad = adenosine. 

Enantiomers of phenyl-[ H5]phenylmethanol were separated by reversed-phase HPLC based on the isotopic chirality using cellulose tribenzoate-coated silica as a stationary phase and 2-propanol/hexane (5 95, v/v) mixture as a mobile phase. The stationary phase showed preferential retention of R)- — enantiomer with a separation factor of 1.008. Complete separation was achieved by a recycle column system after 65 cycles. 

Kimata K, Hosoya K, Araki T, and Tanaka N (1997) Direct chromatographic separation of racemates on the basis of isotopic chirality. Analytical Chemistry 69 2610-2612. 

Keywords Amplification of ee Asymmetric autocatalysis Automultiplication Chiral discrimination Circularly polarized light Quartz Isotope chirality Origin of chirality Pyrimidyl alkanol Spontaneous absolute asymmetric synthesis... 

Carbon-isotope chirality is experimentally difficult to discriminate because the chirality originates from the very small difference between the carbon-12 and carbon-13. Therefore, it has been a question whether isotopically substituted carbon chiral compounds can induce chirality in some enantioselective reactions. To address this problem, we performed asymmetric autocatalysis triggered by a chiral compound arising solely from carbon-isotope substitution. 

This is the first example of the chiral effect, that is, asymmetric induction by carbon isotopically chiral compounds. The neglected carbon-isotope chirality of... 

Scheme 14 Asymmetric autocatalysis triggered by carbon isotopically chiral diphenylmethanol...

Kawasaki T, Shimizu M, Nishiyama D, Ito M, Ozawa H, Soai K (2009) Asymmetric autocatalysis induced by meteoritic amino acids with hydrogen isotope chirality. Chem Commun 4396 398. doi 10.1039/b908754k... 

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. 

---