152419-70-0Relevant articles and documents
Inverting Small Molecule–Protein Recognition by the Fluorine Gauche Effect: Selectivity Regulated by Multiple H→F Bioisosterism
Bentler, Patrick,Bergander, Klaus,Daniliuc, Constantin G.,Mück-Lichtenfeld, Christian,Jumde, Ravindra P.,Hirsch, Anna K. H.,Gilmour, Ryan
, p. 10990 - 10994 (2019/07/12)
Fluorinated motifs have a venerable history in drug discovery, but as C(sp3)?F-rich 3D scaffolds appear with increasing frequency, the effect of multiple bioisosteric changes on molecular recognition requires elucidation. Herein we demonstrate that installation of a 1,3,5-stereotriad, in the substrate for a commonly used lipase from Pseudomonas fluorescens does not inhibit recognition, but inverts stereoselectivity. This provides facile access to optically active, stereochemically well-defined organofluorine compounds (up to 98 % ee). Whilst orthogonal recognition is observed with fluorine, the trend does not hold for the corresponding chlorinated substrates or mixed halogens. This phenomenon can be placed on a structural basis by considering the stereoelectronic gauche effect inherent to F?C?C?X systems (σ→σ*). Docking reveals that this change in selectivity (H versus F) with a common lipase results from inversion in the orientation of the bound substrate being processed as a consequence of conformation. This contrasts with the stereochemical interpretation of the biogenetic isoprene rule, whereby product divergence from a common starting material is also a consequence of conformation, albeit enforced by two discrete enzymes.
Enzyme-catalyzed desymmetrization of meso-skipped polyols to useful chiral building blocks
Bonini,Racioppi,Viggiani,Righi,Rossi
, p. 793 - 805 (2007/10/02)
The biocatalytic desymmetrization, in presence of different enzymes, of two models of polyfunctionalized diols in a meso form was studied. PFL was found to be the most selective enzyme with excellent results in chemical and optical yield with some of the tested substrates. The obtained chiral building block was utilized for some useful synthetic transformations toward the synthesis of natural products.
