Elsevier

Journal of Biotechnology

Volume 168, Issue 2, 20 October 2013, Pages 201-207
Journal of Biotechnology

Lipase-catalyzed enantioselective synthesis of (R,R)-lactide from alkyl lactate to produce PDLA (poly D-lactic acid) and stereocomplex PLA (poly lactic acid)

https://doi.org/10.1016/j.jbiotec.2013.06.021Get rights and content

Highlights

  • Among many tested lipases and proteases only CALB catalyzed the synthesis of D-lactide from alkyl lactate.

  • Enatiopurity of produced D-lactide was over 99.5%.

  • Removal of methanol using molecular sieve was critical to increase the yield of D-lactide.

Abstract

R-lactide, a pivotal monomer for the production of poly (D-lactic acid) (PDLA) or stereocomplex poly (lactic acid) (PLA) was synthesized from alkyl (R)-lactate through a lipase-catalyzed reaction without racemization. From among several types of lipase, only lipase B from Candida antarctica (Novozym 435; CAL-B) was effective in the reaction that synthesized (R,R)-lactide. Enantiopure (R,R)-lactide, which consisted of over 99% enantiomeric excess, was synthesized from methyl (R)-lactate through CAL-B catalysis. Removal of the methanol by-product was critical to obtain a high level of lactide conversion. The (R,R)-lactide yield was 56% in a reaction containing 100 mg of Novozym 435, 10 mM methyl (R)-lactate and 1500 mg of molecular sieve 5 A in methyl tert-butyl ether (MTBE). The important monomer (R,R)-lactide that is required for the production of the widely recognized bio-plastic PDLA and the PLA stereocomplex can be obtained using this novel synthetic method.

Introduction

Lactide is a cyclic dimer composed of two lactic acid molecules and is used as a monomer for poly (lactic acid) (PLA) synthesis through ring-opening polymerization (Chuma et al., 2008, Du et al., 2007). Two chiral carbon centers of lactic acid induce three different enantiomeric forms of lactide: (R)-lactide, (S)-lactide and (meso)-lactide. The demand for environmentally friendly plastics such as PLA has recently rapidly increased because PLA can be produced from renewable resources and can be biodegraded to H2O and CO2 when it is discharged as waste (Agarwal et al., 1998, Ishida et al., 2005).

In commercial processes, lactide is synthesized by the depolymerization of PLA oligomer using high temperature thermal catalysis and chemical catalysts, such as stannous 2-ethylhexanoate (Sn(oct)2), Sb2O3 and other types of metal alkoxides (Noda and Okuyama, 1999, Ajioka et al., 1995). Because enantiopure PLA exhibits superior characteristics, such as a higher melting temperature and higher impact strength than racemic PLA, several methods, including the enantioselective polymerization of PLA using chemical catalysts, have been suggested for producing chirally pure PLA (Spasski et al., 1996). However, a relatively low molecular weight PLA was obtained, which limited its applications. Commercially adapted processes use enantiopure lactide to yield enantiopure PLA, which requires very pure lactide as a monomer (Fukushima and Kimura, 2006). However, depolymerization at a high temperature to produce lactide may cause significant epimerization of lactide, thereby necessitating further complex purification steps, such as crystallization or column separation to obtain enantiopure lactide (Tsukegi et al., 2007). The strong demands for chirally pure R-lactide have recently increased because the stereocomplex formed between equimolar poly (L-lactic acid) (PLLA) and poly (D-lactic acid) (PDLA) exhibits greatly improved properties, such as a high melting temperature and high mechanical strength (Tsuji, 2005, Radano et al., 2000). In this study, the lipase-catalyzed synthesis of enantiopure lactide was proposed to provide the pivotal monomer (R,R)-lactide required for the production of both enantiopure PDLA and stereocomplex PLA.

Whereas traditional chemical processes require harsh reaction conditions, the lipase-catalyzed reaction can be achieved under mild reaction conditions with excellent selectivity (Jacobsen et al., 2003, Leonard et al., 2007, Kim et al., 2007).

Section snippets

Enzymes and regents

Amano lipase A, M, AK, G, PS, and F-AP15 were acquired from Amano Enzyme Inc. (Nagoya, Japan). Lipozyme RMIM, Lipozyme TLIM, and Novozym 435 were purchased from Novozymes A/S (Badsvaerd, Denmark). Lipase GLC, Lipase PLG, and Lipase TL were sourced from Meito Sangyo (Nagoya, Japan). The other enzymes were purchased from Sigma–Aldrich (St. Louis, MO, USA). All of the organic compounds were dried using molecular sieve 3A. Molecular sieves 4A and 5A were obtained from Acros Organics (Geel,

Screening of lipases for the synthesis of (R,R)-lactide

The newly developed method to synthesize enantiopure (R,R)-lactide from alkyl lactate is depicted in Fig. 1. Many lipases and proteases were tested for the synthesis of (R,R)-lactide (Table 1). Among the various lipases tested, lipase B from Candida antarctica (CAL-B; Novozym 435) and lipase from Rhizomucor miehei (Lipozyme RMIM), but not other lipases, were able to catalyze the synthesis of (R,R)-lactide. Because the amount of (R,R)-lactide catalyzed by Lipozyme RMIM was negligible compared

Conclusion

Enantiopure (R,R)-lactide was obtained through an enzyme-catalyzed reaction. This novel synthetic method can supply the important monomer, (R,R)-lactide, that is required for the production of the widely recognized bioplastic PDLA and stereocomplex PLA.

Acknowledgements

We gratefully acknowledge the support of the Ministry of Knowledge Economy, Converging Research Center Program NRF (Grant No. 2011K000661) and Kwangwoon University 2013 Research Grant.

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