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

• Published in: Chemistry : a European journal 2004-07, Vol.10 (14), p.3543-3547
• Main Authors: Ahn, Young-Hoon, Chang, Young-Tae
• Format: Article
• Language: English
• Subjects: boronic acid selector; dynamic combinatorial library; intramolecular acyl migration; molecular amplification; molecular evolution
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200400234

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)Bz3 (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). A molecular evolution model based on a carbohydrate molecule was demonstrated by combining intramolecular acyl migration and kinetic/thermodynamic selectors. Base treatment of myo‐inositol tribenzoate (4) formed a dynamic combinatorial library composed of 12 regioisomers (1–12) in which only one isomer was amplified up to 94 % by the boric acid selector. More interestingly, phenyl boronic acid temporarily amplified the other isomer up to 82 % as a kinetic trap (see scheme).