Chiral, Macrocyclic Oligothiazolines

Significance

An efficient, iterative protocol for the preparation of chiral, macrocyclic oligothiazolines is reported. The thiazolidinone ring system proved highly useful as a protecting group for the β-amino thiol moiety in this synthetic sequence. Head-to-tail oligomerization of intermediate 1 was carried out using the coupling agent BOP-Cl, resulting in a 1.8:1 mixture of cyclic dimer and tri­mer. These species were elaborated to octathia­zoline 2 and dodecathiazoline 3. In contrast, attempts to prepare 2 by cyclization of a hepta­thiazoline precursor failed, most likely due to the conformational inflexibility of the substrate. The authors allude to preliminary results involving the application of these chiral hosts for the recognition of α-hydroxycarboxylic acids.