Lactides racemic

Oxazolones (azlactones) are a form of activated lactones, so they are included in this section. CAL-B is an effective catalyst for the DKR of various racemic four-substituted-5 (4H)-oxazolones, in the presence of an alcohol, yielding optically active N-benzoyl amino acid esters as illustrated in Figure 6.24 [40]. Enantioselective biotransformations of lactides [72,73] and thiolactones ]74] have also been reported. 

The racemic poly(DL-lactide) DL-PLA is less crystalline and lower uelting than the two stereoregular polymers, D-PLA and L-PLA. Further, the copolymers of lactide and glycolide are less crystalline than the two homopolymers of the two monomers. In addition, the lactic acid polymer, because of the methyl group, is more hydrophobic than the glycolide polymer. 

Lactide (LA), the cyclic diester of lactic acid, has two stereogenic centers and hence exists as three stereoisomers L-lactide (S,S), D-lactide (R,R), and meso-lactide (R,S). In addition, rac-lactide, a commercially available racemic mixture of the (R,R) and (S,S) forms, is also frequently studied. PLA may exhibit several stereoregular architectures (in addition to the non-stereoregular atactic form), namely isotactic, syndiotactic, and heterotactic (Scheme 15). The purely isotactic form may be readily prepared from the ROP of L-LA (or D-LA), assuming that epimerization does not occur during ring opening. The physical properties, and hence medical uses, of the different stereoisomers of PLA and their copolymers vary widely and the reader is directed to several recent reviews for more information.736 740-743... 

Ag(carbene)2][AgCl2] (carbene = l,3-dimesitylimidazol-2-ylidene) Was also reported for use as a pre-catalyst for the polymerization of L-lactide with low PDI and in the absence of monomer racemization.69... 

Similarly, a turn-over frequency (TON) of 227 of the polymerization process was distinctly low for 77d with [M]/[I] = 350, at 110 °C for 6 h, using in the melt polymerization conditions. Biocompatible calcium complex 77a used as catalyst at 110 °C produced in 30 min PLAs with high molecular weight (65,000-110,600) and narrow polydispersities (1.02-1.05) using [M]/[I] = 350-700. It is worthy of note that complex 77a displayed a notable heteroselectivity (probability of racemic linkages between monomers, = 0.73, see Sect. 4.2) in polymerization of rac-lactide in THF at 33 °C. Data on the aforementioned calcium initiators and their lactide polymerization are listed in Table 4. 

Spassky and coworkers discovered a remarkable stereocontrol of an enantiomerically pure A1 complex (7 )-161a for the ROP of rac-lactide resulting in a tapered stereoblock PLA microstructure with high melting point =187 °C) (Fig. 26) [160]. Structurally analogous, racemic salen-Al complex 162 resulted in highly isotactic PLA [161]. Feijen s enantiopure chiral complex (RJ )-163 (Fig. 26) exhibited an excellent reverse stereocontrol by preferential polymerization of L-lactide over D-lactide monomer (Kss/Krr = 14) that resulted in PLA with... 

Three cyclic initiators from dibutyltin oxide and 1,2-ethanediol, 2-mer-captoethanol, and 1,2-dimercaptoethane as indicated in Fig. 43 were prepared. Polymerizations of L-lactide and racemic D,L-lactide were conducted... 

Monomers like glycolide or lactide are prepared by heating the corresponding acids under controlled conditions [53]. For example, lactide is prepared by heating lactic acid at 120 °C until water ceases to distill. The temperature is then increased to 140 °C and the pressure is reduced to 10 torn After heating for several hours at this temperature, the pressure is reduced further and the temperature increased until lactide begins to distill. Dilactide (3,6-dimethyl-l, 4-dioxan-2,5-dione) contains two asymmetric centers and therefore exists as L-lactide, D-lac-tide, meso-lactide, and the racemic mixture D,L-lactide and gives polymers with different properties. 

ROP of lactones and lactides using lanthanide alkoxide-based initiators is a relatively recent discovery. The first example of lactone polymerization by lanthanide alkoxide complexes was reported in a DuPont patent written by McLain and Drysdale in 1991 [89]. In general, the activity of these catalysts is much higher than that determined for aluminum alkoxides, especially in lactide polymerization [90-92]. Polymers of relatively high molecular weight and narrow MWD are formed. The negative side-reactions such as macrocycle formation, transesterification, and racemization are absent. 

Coates and co-workers reported polymerizations using both the enantiomerically pure (7) and the racemic (8) Ao-propoxide analogues [21], Complex 8 polymerized rac-lactide iso-selectively producing stereoblock PLA (P = 0.96). The isoselectivity was achieved due to the high selectivity of 7 for RR-lactide and corresponding S -enantiomer for S S -lactide. Further studies of the aluminium-salen system have led to the proposal that several factors influence the polymerization... 

Chiral catalyst 171 was used to effect kinetic resolution of the racemic lactide in the polymerization of the racemic lactide [216]. At low conversion high enantiomeric enrichment in the polymer was observed (Scheme 6.169). The stereochemistry of the catalyst overrides the tendency for syndiotactic placements that are typically favored by chain-end control. At higher conversions, the ee in the polymer decreases. 

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