Solid-phase synthesis of a library of linear oligoester ion-channels

Abstract

A solid-phase synthesis protocol was used to prepare fifteen new linear tetra-, and penta-esters structurally related to an active lead compound. The structures were assembled from three types of hydroxyl protected building blocks: monoalkyl esters of hydroxyglutaric acid, omega-hydroxyacids, and alpha-hydroxymethylalkanoic acids. The standard methodology gave acceptable quantities of material free of small molecule impurities. Mass spectrometric analysis revealed the presence of deletions due to incomplete coupling, as well as additions and macrolactones due to partial acidic rearrangement on release from the solid-support. The amount of these impurities could be estimated from the (1)H NMR spectra, and their implications for subsequent activity analysis are discussed.

Planar-bilayer activities of linear oligoester bolaamphiphiles

“…The solid-phase synthesis of the alkyl oligoesters was previously reported [14]. The phthalate compounds were prepared by a modular methodology (Scheme 2), beginning by reacting terephthaloyl chloride or compound 9 (prepared by a method adapted from [15]) with α,ω-bromoalcohols prepared by mono-brominating the corresponding diols as described [16].…”

Recent synthetic transport systems

“…13). [119][120][121] An elegant solid-phase synthesis approach was conceived to rapidly produce large libraries. As most active members of a small collection, dimer 199 showed high activity in vesicles.…”

Synthesis and ion transport activity of oligoesters containing an environment-sensitive fluorophore

“…† Once in hand, the Trip scaffold was extended into dimeric or trimeric oligoesters by utilizing the ester coupling and deprotection reactions previously developed for the Dip compounds. 25 The alkyl 'tails' appended to the hydroxyl terminus of 6 under the standard conditions were either known from previous work (compounds 9 and 11), 23 or easily synthesized from commercially-available starting materials (compound 7). †In all three cases, the ester coupling reactions between the protected alkyl tails and the Trip scaffold 6 were fairly good yielding; 71% for the reaction yielding 8, 73% for 10, and ~60% for each of the 2 steps leading to 14, via 12 and 13.…”

“…Recent efforts from our own lab have involved a series of oligoester ion channels containing both fully-saturated alkyl chains, [22][23][24] as well as a modified diphenylacetylene or 'Dip' moiety. 25 The Dip molecules exhibit environment-sensitive fluorescence due to the diphenylacetylene chromophore, [26][27][28] this allowed direct detection of partitioning dynamics which in turn lent support to a proposed mechanism based on rate-limiting aqueous phase aggregation.…”