Bifunctional Bisamphiphilic Transmembrane Building Blocks for Artificial ­Signal Transduction

Abstract

A convergent modular total synthesis is described which affords bisamphiphilic bifunctional transmembrane building blocks useful for artificial signal transduction across membranes. The concept relies on direct Glaser-Hay coupling of lithocholic or cholenic acid propargyl esters, carrying recognition or signaling units on their opposite hydroxy functionalities. For catechol recognition, a 2-(aminomethyl)phenylboronic acid was introduced, while the ammonium alcohol was targeted by a bisphosphonate dianion. Signaling units comprised an N-protected cysteine (thiol nucleophile) and an N-protected cysteine/pyridine disulfide, respectively (disulfide substrate). All these polar headgroups were connected to the hydroxy of the lipid core by ester formation.