Cyclic esters and cyclodepsipeptides derived from lactide and 2,5-morpholinediones

Abstract

The reaction between Bu n Li in benzene and the solid polystyrene support PS-C 6H4CH2NH2 leads to a lithiated species that can be represented as PS-C 6H4CH2NHLi(LiBu)x, where x ϳ 4, which is active in the ring-opening of the cyclic esters L-lactide, rac-lactide, and 2,5-morpholinediones. With Ϸ10 eq of these monomeric six-membered rings and with heating, cyclic esters (MeCHC ( dynamic combinatorial library ͉ ring enlarging T he ring-opening polymerization of cyclic esters such as lactides (LA) is a well established procedure for the production of polyesters (1). This is commonly brought about by the use of metal catalyst precursors, although organic catalysis is possible by employing a nucleophilic base such as 4-dimethyl aminopyridine or an N-heterocyclic carbene with alcohol initiators (2-5). It is now generally accepted that metal-alkoxide species are the key reactive intermediates in the propagation steps and, furthermore, that these, too, play a role in the competing side reactions of transesterification and chain transfer (6). These reactions are collectively shown in Scheme 1.Transesterification is normally a deleterious side reaction because it leads to a loss of control of molecular mass in a living polymerization and, because in a stereoselective ring-opening polymerization, transesterification scrambles the stereocenters along a chain. As shown in Scheme 1, transesterification can occur by a bimolecular mechanism or a reaction involving a single chain. The latter reaction, intrachain transesterification leads to cycles. Previously, we found that the polymerization of lactide by Ph 2 SnX 2 initiators, where X ϭ OPr i or NMe 2 , gave different ratios of chains to cycles with the cycles being significantly more prominent for X ϭ NMe 2 . This apparently arises because of the favorable chelation of the SnOCHMeC(O)NMe 2 groups (7).Prompted by these observations, we set out to explore a synthetic route for cyclic oligoesters derived from LA and we describe herein our findings. It is worthy of mention that others have synthesized cyclic esters and carbonates principally as a route for the formation of polyesters and polycarbonates (8). Brunelle and coworkers (9) at GE Corporate Research andDevelopment specifically developed high-yielding syntheses of cyclic esters derived from 1,4-aromatic acyl chlorides and diols. These ringed compounds melt to yield low viscous media, which by a thermo-neutral ring-opening polymerization give polyesters with no elimination products. This chemistry forms the technology platform of Cyclics Corporation. 2. Kricheldorf and coworkers (10, 11) have used principally tin(IV) diolates as initiators for the ring-opening polymerization and the reaction with dicarboxylic acid chlorides to cleave the cyclic esters. 3. Hodge and coworkers (12) used a solid support and step growth polymerization to produce a polyester chain followed by treatment with a metal catalyst, most often Bu n 2 SnO, to affect intrachain transesterification and release of the cyclic esters to the solution phase. 4....

Synthesis of a Regular 24-membered Cyclodepsipeptide by Direct Amide Cyclization

“…The inverted configuration may promote a different conformation that is more suitable for the attack of the ω-hydroxy group onto the oxazolone moiety. A comparable observation was reported recently [25]: The base-catalyzed cyclooligomerization of (3S,6S)-3-isopropyl-6-methylmorpholine-2,5-dione led to cyclic di-, tri-, and tetramers, i. e., cyclic depsipeptides with alternating lactic acid and valine units, with extensive epimerization. For example, one of the isomeric 24-membered rings was obtained in crystalline form, and the X-ray crystal structure determination established the (R,R,R,S,R,R,R,S)-configuration with only two valine residues showing the original (S)-configuration.…”

Zwitterionic ring opening polymerization of lactide by metal free catalysts: Production of cyclic polymers

“…46,47 Cyclic PLA with 3 (20 repeating units has been found to be an important antitumor agent. 44,45 In addition, cyclic PLA could be used as macromonomer to prepare high molecular weight linear PLA homopolymers and copolymers by ring opening polymerization. Since these polymers are produced by metal free catalysts they can be used in medical and microelectronic applications.…”

“…43 Low molecular weight cyclic PLA was previously prepared by using lithium alkyls. 44,45 The synthesis of high molecular weight macrocyclic polymers is a great challenge in polymer chemistry. Cyclic poly (lactide) is a kind of large-ring macromolecule which is a structurally constrained compared with linear PLA.…”

Percolation of Trace Amounts of Linear Polymers in Melts of Cyclic Polymers

“…[1][2][3][4][5] The anomalous dynamic behavior of a melt of CPs is also an important long-standing problem in polymer physics. As McLeish [6] notes in a recent commentary, ''[new ideas] are being stimulated by one polymer architecture that still eludes a quantitative model of any kind: the ring.…”