SYNTHETIC METHODS FOR ESTER BOND FORMATION AND CONFORMATIONAL ANALYSIS OF ESTER-CONTAINING CARBOHYDRATES

Author

Sven Hackbusch, University of the Pacific

Date of Award

2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Chemistry

First Advisor

Andreas Franz

First Committee Member

Vyacheslav V. Samoshin

Second Committee Member

Liang Xue

Third Committee Member

Jianhua Ren

Fourth Committee Member

Wade A. Russu

Abstract

This dissertation encompasses work related to synthetic methods for the formation of ester linkages in organic compounds, as well as the investigation of the conformational influence of the ester functional group on the flexibility of inter-saccharide linkages, specifically, and the solution phase structure of ester-containing carbohydrate derivatives, in general.

Stereoselective reactions are an important part of the field of asymmetric synthesis and an understanding of their underlying mechanistic principles is essential for rational method development. Here, the exploration of a diastereoselective O-acylation reaction on a trans-2-substituted cyclohexanol scaffold is presented, along with possible reasons for the observed reversal of stereoselectivity dependent on the presence or absence of an achiral amine catalyst. In particular, this work establishes a structureactivity relationship with regard to the trans-2-substituent and its role as a chiral auxiliary in the reversal of diastereoselectivity.

In the second part, the synthesis of various ester-linked carbohydrate derivatives, and their conformational analysis is presented. Using multidimensional NMR experiments and computational methods, the compounds’ solution-phase structures were established and the effect of the ester functional group on the molecules’ flexibility and three-dimensional (3D) structure was investigated and compared to ether or glycosidic linkages. To aid in this, a novel Karplus equation for the C(sp2)OCH angle in esterlinked carbohydrates was developed on the basis of a model ester-linked carbohydrate. This equation describes the sinusoidal relationship between the C(sp2)OCH dihedral angle and the corresponding 3JCH coupling constant that can be determined from a JHMBC NMR experiment. The insights from this research will be useful in describing the 3D structure of naturally occurring and lab-made ester-linked derivatives of carbohydrates, as well as guiding the de novo-design of carbohydrate based compounds with specific shape constraints for its use as enzyme inhibitors or similar targets.

In addition, the above project led to the development of a methodology for the synthesis of symmetrical ester molecules from primary alcohols using a mild oxidative esterification reaction, which proceeds in hydrous solvents using a nitrosyl radical catalyst. The reaction could be performed with a variety of alcohols and the resulting compounds are of interest in the fragrance and flavor industries.

Pages

430

Recommended Citation

Hackbusch, Sven. (2017). SYNTHETIC METHODS FOR ESTER BOND FORMATION AND CONFORMATIONAL ANALYSIS OF ESTER-CONTAINING CARBOHYDRATES. University of the Pacific, Dissertation. https://scholarlycommons.pacific.edu/uop_etds/4164