A New Generation of "Cholaphanes": Steroid-Derived Macrocyclic Hosts with Enhanced Solubility and Controlled Flexibility

Khadga M. Bhattarai, Anthony P. Davis*, Justin J. Perry, Christopher J. Walter, Stephan Menzer, David J. Williams

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

The macrocyclic "cholaphanes" 3a - c were synthesized from the inexpensive steroid cholic acid. Like earlier relatives they feature substantial cavities with inward-directed hydroxyl groups, suitable for binding polar molecules such as carbohydrates in nonpolar media. New features are the externally directed alkyl chains, promoting solubility in organic solvents, and (in the case of 3b/c) reduced conformational freedom resulting from truncation of the steroidal side-chain. In particular, modeling shows that the smallest macrocycle 3c possesses very little flexibility, preferring an open conformation which is also revealed in the X-ray crystal structure of its pentahydrate. NMR studies indicated that all three cholaphanes form 1:1 complexes with octyl β-D-glucoside in CDCl3, with Ka = 600-1560 M-1. Cholaphanes 3b/c proved able to extract methyl β-D-glucoside from aqueous solutions into CHCl3. The transport of methyl β-D-glucoside across a chloroform barrier was also demonstrated for 3c.

Original languageEnglish
Pages (from-to)8463-8473
Number of pages11
JournalJournal of Organic Chemistry
Volume62
Issue number24
DOIs
Publication statusPublished - 28 Nov 1997
Externally publishedYes

Fingerprint

Dive into the research topics of 'A New Generation of "Cholaphanes": Steroid-Derived Macrocyclic Hosts with Enhanced Solubility and Controlled Flexibility'. Together they form a unique fingerprint.

Cite this