Lactides stereoisomers

Due to its stereogenic center, lactic acid exists in two enantiomeric forms (d- and L-lactic acid), leading to three different lactide stereoisomers (d-, l- and mesolactide). Depending on the relative amounts of the different stereoisomers in the final polyester, the crystallinity of the resulting PLA is heavily influenced and this way the properties of the polymer can be adjusted to satisfy the needs of different applications [18-20]. 

Homodecoupled NMR spectra can be used to quantitatively determine the composition of D-lactide and meso-lactide stereoisomer impurities in polylactide containing predominantly L-lactide [5]. 

Fig. 3.9 Stereoisomerism of lactide and poly(lactic acid), a The three lactide stereoisomers D-lactide, L-lactide, and meso-lactide. b Stereosequences of poly(lactic acid) (Reproduced from Dove et al. [44] with permission of The Royal Society of Chemistry)...

Many investigators have studied the in vivo degradation kinetics of lactide/glycolide materials (5,35-39). There has been some confusion in the interpretation of results primarily because of lack of consistency in nomenclature and careful attention in describing the specific stereoisomers evaluated. Nevertheless, the overall degradation kinetics are fairly well established for the entire family of homopolymers and copolymers. At the present, this common knowledge of the in vivo lifetimes of various lactide/glycolide polymers is a primary reason for their popularity. 

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... 

Besides the investigation of stereoisomers, the degradation of copolymers with E-caprolactone [24, 28, 29], 5-valerolactone [24, 28, 29], y-butyrolacton [30] and D,L-lactide [31] were also studied. The trends are found to be independent of the co-monomer. Co-monomer units within the polymer lead to an increase of degradation rate up to ten times that of natural PHB. The reason for this finding is the change of crystallinity within in the synthetic material, which could by proved by various DSC measurements of different copolymers and compositions. 

Three possible stereoisomers of lactide (LA) exist d-, l- and me o-lactide (Figure 1). A racemic mixture of d- and L-lactide is referred to as rac-lactide (rac-LA)."° The stereochemistry of these monomers, when incorporated into a polymer chain, creates material with a certain stereocomplexity or tacticity. " The tacticity of a given PLA sample may be defined by two parameters P [probability of forming adjacent stereocenters with the same chirality or a meso (m) linkage] and P [probability of... 

Monomers Figure3.8 shows a small selection of cyclic monomers suitable for ROP [43]. Additionally, three different stereoisomers of lactide exist as a consequence of the presence of two stereocenters per monomer unit, namely meso-, L- and d-lactide, see Fig. 3.9. Further, racemic mixture of L- and D-lactide are commercially available. While ROP of either pure l- and D-lactide enables synthesis of highly crystalline poly(L-lactic acid) or poly(D-lactic acid), ROP of rac- or wcj< -lactide with adequate catalysts allows the synthesis of stereoblock copolymers, heterotactic and syndiotactic poly(lactic acid). Notably, stereoregular PLAs display much lower rates of degradation than the amorphous atactic polymer. 

Over the past several decades, polylactide - i.e. poly(lactic acid) (PLA) - and its copolymers have attracted significant attention in environmental, biomedical, and pharmaceutical applications as well as alternatives to petro-based polymers [1-18], Plant-derived carbohydrates such as glucose, which is derived from corn, are most frequently used as raw materials of PLA. Among their applications as alternatives to petro-based polymers, packaging applications are the primary ones. Poly(lactic acid)s can be synthesized either by direct polycondensation of lactic acid (lUPAC name 2-hydroxypropanoic acid) or by ring-opening polymerization (ROP) of lactide (LA) (lUPAC name 3,6-dimethyl-l,4-dioxane-2,5-dione). Lactic acid is optically active and has two enantiomeric forms, that is, L- and D- (S- and R-). Lactide is a cyclic dimer of lactic acid that has three possible stereoisomers (i) L-lactide (LLA), which is composed of two L-lactic acids, (ii) D-lactide (DLA), which is composed of two D-lactic acids, and (iii) meso-lactide (MLA), which is composed of an L-lactic acid and a D-lactic acid. Due to the two enantiomeric forms of lactic acids, their homopolymers are stereoisomeric and their crystallizability, physical properties, and processability depend on their tacticity, optical purity, and molecular weight the latter two are dominant factors. 

Figure 4.1 Stereoisomers of lactide monomers (reproduced with Elsevier s permission from Ref. 9).

The stereocopolymers of lactic acid, prepared by the polymerization of various stereoisomers, are discussed in a subsequent section in this book and will not be discussed here. Typical comonomers that have been used for lactic acid or lactide copolymerization are glycolic acid or glycolide (GA) [11-17], poly (ethylene glycol) (PEG) or poly(ethylene oxide) (PEG) [15 3], poly(propylene oxide) (PPO) [16-18], (7 )- 3-butyrolactone (BL), 6-valerolactone (VL) [44-46], E-caprolactone (CL) [47-54], 1,5-dioxepan-2-one (DXO) [55-60], trimethylene carbonate (TMC) [61],... 

Both L- and o-lactic acid stereoisomers are naturally occurring however, most of the lactic acid in nature is L-type or sometimes racemic. The fact that lactic acid that is produced in the human body is in the L-enantiomeric form and the interest in the biomedical applications of this polymer have led both research and production to concentrate on L-lactide or OL-lactide polymers [16-18]. The o-isomer does not have many applications, except for use in particular medicinal chemicals. 

As already described, PLA can be manufactured to give a wide range of properties because of the chiral nature of lactide. The mechanical characteristics of PLA are known to depend on the choice and distribution of stereoisomers within the polymer chains. High-purity l- and D-lactide form stereoregular isotactic PLLA and PDLA, respectively, with equivalent physicochemical and mechanical properties. These are semicrystalline polymers with a high around 175-180°C and a Tg in the 60-70°C range. The racemic d,l-lactide and mc o-lactide, on the other hand, form atactic POLL A and mcio-poly(lactide), which are amorphous materials [30-32]. 

Caimcross et al. [16] studied moisture sorption and transport in three different PLA films (high percentage l-lactide, a mixture of lactic acid stereoisomers, and a 50 50 blend of PLLA and PDLA) exposed to RH changes from 0 to approximately 25% at 40°C using a quartz crystal microbal-ance/heat conduction calorimeter (QCM/HCC). In addition, moisture transport, crystallization, and degradation in PLA... 

When the vine-twining polymerization was conducted using optically active polyesters, poly(lactide)s (PLAs), which had three kinds of the stereoisomers, i.e., poly(L-lactide) (PLLA), poly(D-lactide) (PDLA), and poly(DL-lactide) (PLDLA), as guest polymers, the author found that amylose, produced by the enzymatic polymerization, perfectly recognized the chirality in PLAs on complexation and... 

However, ring-opening polymerisation of the lactide, as practised by Cargill, appears more advantageous. The latter is polymerised in the presence of tin/zirconium or titanium catalysts (this technique is also used to polymerise lactones, e.g. caprolactone on the large scale). Lactide, rather like lactic acid, but now possessing two asymmetric carbon atoms within its structure can exist as three stereoisomers L-lactide, D-lactide, and the meso-lactide (see Figure 10.9). 

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