Chiral Phosphate Groups

Mikami and Yoshida extended the scope of this method considerably by using propargyl phosphates and chiral proton sources [94], The propargylic phosphates thereby have been found to be advantageous owing to their high reactivity towards palladium and the extremely low nudeophilicity of the phosphate group [95]. In some cases, it was even possible to obtain allenes from primary substrates, e.g. ester 194 (Scheme 2.60) [96]. A notable application of this transformation is the synthesis of the allenic isocarbacydin derivative 197 from its precursor 196 [97]. 

After having proven that BINOL phosphates serve as organocatalysts for asymmetric Mannich reactions, Akiyama and Terada et al. reasoned that the concept of electrophilic activation of imines by means of chiral phosphoric acids might be applicable to further asymmetric transformations. Other groups recognized the potential of these organocatalysts as well. They showed that various nucleophiles can be used. Subsequently, chiral phosphates were found to activate not only imines, but also other substrates. 

Evidence for an in-line SN2-like mechanism of most enzymatic phospho group transfer reactions comes largely from study of chiral phospho groups.663/692-695 A chiral phosphate can be introduced at either the a or (3 phosphorus of ATP by substitution of one of the oxygen atoms by sulfur. A chiral phospho group in the P position can be formed by substituting one oxygen by S and a second by lsO. 

Fig. 7 Schematic view of the different approaches used to model the chiral interactions between DNA double helices, (a) DNA duplexes are viewed as clean cylinders with charged helical patterns of negative phosphates and positive adsorbed counterions. Reproduced with permission from [18], (b) Duplexes interact via steric interlocking of backbone and grooves and through electrostatic repulsion of the phosphate groups. Reproduced with permission from [14]...

The reaction of the tetrabutylammonium salt of cAMP with 4-(bromo-methyl)-2Jf-chromen-2-one yields two products which result from axial and equatorial attack of the phosphate group. What is the isomeric relationship between the two products Determine the configuration of all the chirality centres in both products. 

The first chiral phosphates to be used for stereochemical analyses were chiral phosphorothioates, which were used to determine the stereochemical courses of ribonuclease, UDP-glucose pyrophosphorylase, adenylate kinase and several other kinases and synthetases. The chiral phosphorothioates either had sulfur in place of an oxygen at an otherwise prochiral center of a phosphodiester or phosphoanhydride or stereospecifically placed sulfur and 180 (or nO) in a terminal phosphoryl group. The syntheses and configurational analyses of the most important of these compounds are outlined in the following. 

J.R. Knowles and associates have devised two methods for analyzing the configurations of the chirally enriched phosphate group in (S)- 1,2-propanediol-1 -[l6Ot l70, lsO]phosphate [58,59], They have described their methods in detail elsewhere [5], so the present discussion has been abridged, with the intention of conveying the principles upon which the analyses are based, while avoiding an extended discussion of factors which complicate them. 

If the phosphorotropic rearrangement is combined with selective electrophilic substitution of free phenolic units (e.g. bromination) and hydrolysis of ester or phosphate groups a variety of inherently chiral calixarenes becomes available,130 as demonstrated by the examples in Figure 15. 

A -oxides) In sulfones, the sulfur bonds with a tetrahedral array, but since two of the groups are always oxygen, no chirality normally results. However, the preparation of an optically active sulfone (2) in which one oxygen is and the other illustrates the point that slight differences in groups are all that is necessary. This has been taken even further with the preparation of the ester 3, both enantiomers of which have been prepared. Optically active chiral phosphates 4 have similarly been made. ... 

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