Molecular Evolution Using Intramolecular Acyl Migration on myo‐Inositol Benzoates with Thermodynamic and Kinetic Selectors

Abstract

A molecular evolution model was successfully demonstrated by combining the intramolecular acyl migration on inositol tribenzoates and boron selectors. The addition of boric acid to 12 members of DCL (dynamic combinatorial library) induced the dramatic amplification of myo-I(2,4,6)Bz(3) (1) with up to 94 % under thermodynamic (see Figure 1 c) control while a portion of phenyl boronic acid caused two significant different distributions: under kinetic control, the pre-equilibrium of DCL shifted to induce the exclusive amplification of 1,4,6-tribenzoyl myo-inositol (7) with decrease of other members up to 82 % from the mixture (see Figure 2 b), and changed gradually to form 2,4,6-tribenzoyl myo-inositol (1) with up to 96 % under thermodynamic control (Figure 2 c).

Mechanisms of Stereodirecting Participation and Ester Migration from Near and Far in Glycosylation and Related Reactions

“…For myo -inositol, the same authors also demonstrated that different boranes could yield different products . Starting from 1,4,5-tri- O -benzoyl- myo -inositol, a 94% yield of 2,4,6-tri- O -benzoyl- myo -inositol was obtained by use of boronic acid as additive.…”

“…For myo-inositol, the same authors also demonstrated that different boranes could yield different products. 335 Starting from 1,4,5-tri-O-benzoyl-myo-inositol, a 94% yield of 2,4,6-tri-Obenzoyl-myo-inositol was obtained by use of boronic acid as additive. With phenylboronic acid, however, 1,4,6-tri-Obenzoyl-myo-inositol was first obtained as the main product in 82% yield, but after 7 h, 2,4,6-tri-O-benzoyl-myo-inositol was the main product in 96% yield (Scheme 54).…”

The Dynamic Covalent Chemistry of Esters, Acetals and Orthoesters

“…Addition of a bidentate pyridyl ligand as a template led to a significant amplification of the dimeric product (sixfold increase). Chang and co‐workers investigated the acyl migration on myo ‐Inositol benzoates under basic conditions (Scheme , b) . When 1,4,5– 3 was treated with DBU (1,8‐diazabicyclo[5.4.0]undec‐7‐ene) in anhydrous acetonitrile, a dynamic library of twelve isomers was obtained.…”

“…a) Palladium‐catalyzed transesterification of allylic esters (Sanders, 2000) . b) Dynamic evolution of an inositol ester library (Chang, 2004) …”

Chemical Genetics

“…When a template or ligand is used to amplify the concentration of a member of the library, so-called “survival of the fittest”, the Darwinian implications of this often lead it to being referred to as “molecular evolution”. In a molecular evolution system, the fittest binder is amplified with each successive round of screening, whereas the poor binders' concentration will either be unaffected or decrease. ,, Though widely applied for many other purposes, DCLs have also been used to identify protein ligands, which makes them a promising tool for library development in chemical genetics. − …”