Supramolecular chemistry : A bile acid based approach

Abstract

Chapter 1 Contains three parts: Part A – Describes the design, synthesis, and evaluation of a bile acid-based adenine/biotin receptor. Part B – Discusses the site-specificity of adenine binding observed for aliphatic and aromatic carboxylic acids. Part C – Depicts the construction and assessment of a bile acid-based molecular tweezer possessing guaiazulene moieties for the recognition of electron-deficient aromatic substrates.

Chapter 2 Related to the chemistry of Tröger’s base derivatives and divided into two parts: Part A – Analyzes the effect of spacers on diastereoselection in bile acid-derived template-directed asymmetric synthesis of Tröger’s base analogs. Part B – Describes the synthesis of a novel class of Tröger’s base derivatives.

Chapter 3 Depicts the progress attained in the program to construct bile acid-based hyperbranched molecules.

Chapter 1 Details Part A The receptor 1 bearing a pair of convergent carboxyl groups was designed following molecular modeling and synthesized in a sequence of three simple steps. Receptor 1.1.5 was found to bind 9-butyladenine and biotin methyl ester in CDCl? at 27°C with association constants of 3,500 M?¹ and 1,700 M?¹, respectively.

Part B A carboxylic acid can bind a 9-alkyladenine derivative via the Watson-Crick (WC) mode or the Hoogsteen (HG) mode. 9-butyladenine was titrated with three aromatic and three aliphatic carboxylic acids.

Binding of aromatic carboxylic acids showed exclusive and, in one case, a predominant downfield shift of the 8-H signal. Binding of aliphatic carboxylic acids was accompanied by a predominant upfield shift of the 2-H signal.

These observations were correlated with the preponderance of the HG type of complex for aromatic carboxylic acids and WC type of complexes for aliphatic carboxylic acids.

Part C The first example of a synthetic receptor 1.3.4 comprising an azulene derivative (guaiazulene) was synthesized on the methyl deoxycholate backbone.

Host 1.3.4 showed K? = 5 M?¹ with picric acid and 13 M?¹ with trinitrofluorenone in CDCl? at 27°C. Binding improved considerably in nonpolar media. Following an extraction-based protocol, compound 2 was found to bind picric acid with K? = 55 M?¹ in CCl? and 225 M?¹ in cyclohexane:CCl? (1:1) at 26°C.

Chapter 2 Details Part A The effect of spacer length on diastereoselective coupling of aniline fragments to form Tröger’s base analogs (2.1.8, 2.1.9, 2.1.10 and their diastereomers) was examined. Under cyclization conditions involving trifluoroacetic acid and urotropine, the diastereoselection altered with changing spacers. Part B A new class of Tröger’s base analogs (2.2.1, 2.2.2) containing carboxyl-appended phenyl rings were synthesized. Compounds 2.2.1 and 2.2.2 were found to be almost insoluble in common organic solvents like CHCl?, CH?Cl?, etc. However, in derivative 2.2.15, the insolubility was overcome by design.