Polymer-supported syntheses of cyclic oligodepsipeptides

Polymer-supported syntheses of oxo-crown ethers and derivatives containing α-amino-acid residues

“…In preliminary experiments the cyclic products were contaminated with significant amounts of linear products and it soon became clear that with this particular PS hydroxy-ester the beads, catalyst and solvent all needed to be dried carefully before use. Presumably, unlike the previous PS hydroxy-esters [10,11], the PS hydroxy-ester derived from hydroxy-acid 4 tends to be significantly hygroscopic and in the presence of the catalyst the traces of moisture serve as nucleophiles resulting in detachment of the linear chains.…”

“…k By the gain in weight of the beads PS hydroxy-amide 15 obtained in 52% yield. l Loading of amino acid 0.98 mmol/g based on elemental analyses for N and Cl [11]. By the gain in weight of the beads PS hydroxy-amide 16 obtained in 73% yield.…”

“…The use of these new hydroxy-esters is of interest as the cyclic oligomers produced are oxo-crown ethers, or their derivatives, and they are expected to have interesting recognition properties [22,23]. Moreover, they are expected to be more soluble in polar solvents than their hydrocarbon chain counterparts [10,11]. Thus, for potential recognition purposes the present type of macrocycles are more interesting than those prepared previously by this PS method.…”

“…Thus, filtering off the beads at the end of a cyclo-oligomerization affords a solution of an homologous family of macrocyclic oligomers. Whilst the mechanism of the catalysis by di-nbutyltin oxide is not completely clear [11], since linear chains remain attached to the beads it appears that the ester carbonyl group is only subjected to nucleophilic attack after the di-n-butyltin oxide, or a derivative generated in situ, binds to the carbonyl group and/or reacts with 1381-5148/$ -see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.reactfunctpolym.2008.06.003 the terminal hydroxyl group.…”

“…Another attractive feature of the present method is that it lends itself to the synthesis of the required hydroxy-esters on the beads. Thus, PS hydroxy-esters 1 and 2 [10] and hydroxyacylpeptides 3 [11] have all been prepared on the beads and then cyclo-oligomerized.…”