MECHANISTIC STUDIES AND SYNTHETIC APPLICATIONOF MONOHYDROLYSIS OF SYMMETRIC DIESTERS

The hydrolysis of esters is among the most common and useful reactions in organic chemistry. The monohydrolysis of symmetric diesters can produce half esters, which form intermediates for total syntheses of various important compounds. However, the efficiency for the monohydrolysis of symmetric diesters is low by classical saponification. In order to obtain high yields of products of monohydrolysis from symmetric diesters, enzymes are used in total syntheses. However, because mechanisms of enzyme reactions are not well understood, they often require extensive screening with no clue for the mononhydrolysis of symmetric diesters. Due to these reasons, a new method has been proposed and developed, which can produce a very high yield up to 99% for the mononhydrolysis of symmetric diesters. In this research, we studied co-solvent effects for the reaction rate in the monohydrolysis reaction. Moreover, we expanded the research result of the co-solvent system from organic-aqueous systems to polar-less polar systems, which are used for the drug conjugation, pegylation and coupling reaction. The product of the mononhydrolysis of symmetric dimethyl bicyclo[2.2.1] hept-2,5-diene-2,3-dicarboxylate was used as the starting material for the total synthesis of CMP-New5AC mimics and an important intermediate for the syntheses of natural products with the methylene-bicylo[2.2.1] heptane framework. Asymmetric monohydrolysis of dimethyl bicyclo[2.2.1] Texas Tech University, Hezhen Wang, December 2010 viii hept-2,5-diene-2,3-dicarboxylate was studied without enzymes. In addition, chiral phase transfer catalysts, chiral bases, chiral ionic liquids and chiral catalysts were examined for the asymmetric reaction.