Quantitative structure-activity relationship chirality

The ubiquitous involvement of these materials in chirality induction for the purposes of assaying small molecules, determining enantiomeric purities, quality control, and quantitative structure-activity relationships (QSAR) is reviewed later in this article. The detector that is common to all these applications is CD. 

Because of fhe stereospecifity of biological effects, QSAR (quantitative structure-activity relationships) methods must be capable of taking into account atomic chiralities. Indeed, one of fhe most popular 3D-QSAR methods, CoMFA and other CoMFA-like methods take into account chirality by default, since fhe molecular fields of chiral isomers are different If compounds are highly flexible and no experimental structural information about fhe receptor-ligand complexes is available, CoMFA (and CoMFA-like) methods are not always applicable. Several shortcomings and problems have motivated researchers to consider improvements to these techniques. The first idea for improvement was to modify the conventional 2D descriptors to make them chirahty-sensitive [1]. 

Lehmann, F.P.A. (1987) Stereoselectivity and affinity in molecular pharmacology. Part 12. A quantitative stereo-structure activity relationship analysis of the binding of promiscuous chiral ligands to different receptors. Quantitative Structure-Activity Relationships, 6, 57-65. 

We regard as one the most significant re.su Its of the CSM approach the observation that symmetry and chirality can be used as a predictive structural parameter for biochemical quantitative structure-activity relationship (QSAR) studie.s. An example is the analysis of the correlation between the chirality of the pharmacophores of trypsin inhibitors and their activity. The chirality which was used was the induced one on the side chain of the inhibitor within the active site. A nice, almost linear, correlation was observed between inhibition efficiency and the degree of chirality. ... 

A series of mono- and dialkylated, chiral 1,2-amino-phosphinamide ligands (752) have been successfully applied in the chiral phosphinamide-Zn(ii) catalysed asymmetric Henry reaction between benzaldehyde and nitromethane (Scheme 210). The effects of the N-substituent sizes of chiral ligands (752) on the enantioselectivities in this reaction have been correlated using a predictive quantitative structure-activity relationship (QSAR) mathematical model. A quantitative correlation model has been also established based on subtractive Sterimol parameters. Ligand optimisation based on the QSAR model led to chiral 1,2-amino-phosphinamide ligand (752a), which produced (R)-p-nitroalcohol (753) in excellent yield (99%) and enantioselectivity (92% ee). ... 

Various magnesium oxide crystals [commercial MgO, CM-MgO (SSA 30 m /g), conventionally prepared MgO, NA-MgO (SSA 250 m /g), aerogel prepared MgO, NAP-MgO (SSA 590m /g)] were initially evaluated in the CSC and AE reactions separately in order to understand the relationship between structure and reactivity. All these MgO samples catalyzed both CSC of benzaldehyde with acetophenone to form chalcone quantitatively and selectively, and subsequent AE using (- -)-diethyl tartrate (DET) as a chiral auxiliary to obtain a chiral epoxy ketone in good yield and impressive ee. The nanocrystalline MgO (NAP-MgO) was found to be more active than the NA-MgO and CM-MgO in the condensation and epoxidation reactions (Figure 5.6). 

---