Candida polymers

In polyester synthesis via ring-opening polymerizations, metal catalysts are often used. For medical applications of polyesters, however, there has been concern about harmful effects of the metallic residues. Enzymatic synthesis of a metal-free polyester was demonstrated by the polymerization of l,4-dioxan-2-one using Candida antarctica lipase (lipase CA). Under appropriate reaction conditions, the high molecular weight polymer (molecular weight = 4.1 x 10" ) was obtained. 

The multipolymer enzymatic resolution of soluble polymer-supported alcohols 42 and 43 was achieved using an immobilised lipase from Candida Antarctica (Novozym 435). The R-alcohol was obtained in enantiomerically pure form (>99% ee) after its cleavage from the poly(ethylene) glycol (PEG) scaffold . The achiral hydantoin- and isoxazoline-substituted dispirocyclobutanoids 47 were produced using both solution and solid-phase synthesis <00JOC3520, OOCC1835>. 

Chemoenzymatic polymerizations have the potential to further increase macro-molecular complexity by overcoming these limitations. Their combination with other polymerization techniques can give access to such structures. Depending on the mutual compatibility, multistep reactions as well as cascade reactions have been reported for the synthesis of polymer architectures and will be reviewed in the first part of this article. A unique feature of enzymes is their selectivity, such as regio-, chemo-, and in particular enantioselectivity. This offers oppormnities to synthesize novel chiral polymers and polymer architectures when combined with chemical catalysis. This will be discussed in the second part of this article. Generally, we will focus on the developments of the last 5-8 years. Unless otherwise noted, the term enzyme or lipase in this chapter refers to Candida antarctica Lipase B (CALB) or Novozym 435 (CALB immobilized on macroporous resin). 

Recent studies in the pharmaceutical field using MBR technology are related to optical resolution of racemic mixtures or esters synthesis. The kinetic resolution of (R,S)-naproxen methyl esters to produce (S)-naproxen in emulsion enzyme membrane reactors (E-EMRs) where emulsion is produced by crossflow membrane emulsification [38, 39], and of racemic ibuprofen ester [40] were developed. The esters synthesis, like for example butyl laurate, by a covalent attachment of Candida antarctica lipase B (CALB) onto a ceramic support previously coated by polymers was recently described [41]. An enzymatic membrane reactor based on the immobilization of lipase on a ceramic support was used to perform interesterification between castor oil triglycerides and methyl oleate, reducing the viscosity of the substrate by injecting supercritical CO2 [42],... 

Williams et al.[13] used a combination of a polymer-bound phosphonium bromide and a cross-linked lipase from Candida rugosa for a resolution process of an -bromo ester (Scheme 5). 

These enzymes can be used to make polyesters, polyacrylates, polysaccharides, polyphenols, and other polymers. An example of such an application was acknowledged with the 2003 Academic Green Chemistry Award to Richard A. Gross for a broad range of lipase-catalyzed polyester syntheses (see Ritter, 2003). The reaction shown in Figure 12.9 occurs under mild conditions and high selectivity using the immobilized lipase B, harvested from the bacterium Candida antarctica. 

The sulfa drug A -[4-sulfamido-A -(5-methyl-3-isoxazolyl)phenyl]maleimide 610, prepared from maleic anhydride and 4-amino-A -(5-methyl-3-isoxazolyl)benzensulfonamide, was polymerized using benzoyl peroxide as a free radical initiator. The polymer showed significant antifungal activity toward both Candida albicans and A. niger <2002EPJ551>. 

Five-membered unsubstituted lactone, y-butyro-lactone (y-BL), is not polymerized by conventional chemical catalysts. However, oligomer formation from y-BL was observed by using PPL or Pseudomonas sp. lipase as catalyst.1523 157 d-Valerolactone (<3-VL, six-membered) was polymerized by various lipases of different origin to give the polymer with Mn of several thousands.148 Another six-membered lactone, l,4-dioxan-2-one, was polymerized by Candida antarctica lipase (lipase CA) to give the polymer with Mw higher than 4 x 104.158 The resulting polymer is expected as a metal-free polymeric material for medical applications. 

The single enantiomer of 45 is produced by enantioselective acylation with vinyl acetate catalysed by Novozym 435, an immobilised lipase from Candida antarctica containing about 1% w/w enzyme on a macroporous polypropylic resin. You will appreciate that as both substrate and catalyst are on polymers, one at least must be soluble in the reaction mixture. The polymer is stripped from the substrate 45 with HF. 

Enzyme-catalysed condensation polymerization of 11-hydroxyundecanoic add with lipase from Candida cylindracea. Polymer, 35 (16), 3576-3578. 

Many of the polymerizations presented in this book proceed in organic solvents. To enhance the stability of enzymes in these solvent systems and to ensure efficient recovery of the biocatalysts the enzymes are commonly immobilized. Chapter 2 reviews some of the new trends of enzyme immobilization on nanoscale materials, while Chapter 3 sheds light on some new approaches to improve the commercial immobilization of Candida antarctica lipase B - the biocatalyst most often employed in enzymatic polymer synthesis. 

Various immobilized lipases were tested in the transesterification of 1-O-octyl a-D-glucopyranoside (1) with ethyl acrylate, using the latter compound both as reactant and solvent. By far the best results were obtained with lipase preparations of the Candida antarctica type (see Table 1). Acylation occurred mainly at the 6-0 position, in line with the usual preference of lipases for primary alcohol functions. The resulting 6-O-acryl ester may serve as a starting material for specialty polymers. Acylation at the 2-O-position was the main side-reaction. The selectivity and rate of the C. antarctica lipase catalyzed reaction could be improved substantially by adding zeolite CaA which selectively adsorbs water and ethanol . ... 

Vaidya, A. Xie, W. Gao, W. Bohling, J.C. Miller, M.E. Gross, R. A. Enzyme immobilization without a support Candida antartica lipase B (CALB) Self-crosslinked aggregates ACS Polymer Preprints, 2006, 47(2), 236. 

Candida antarctica Lipase B (CALB) is atfracting increasing attention as a biocatalyst for the synthesis of low molar mass and polymeric molecules. Almost all publications on immobilized CALB use the commercially available catalyst Novozym 435, which consists of CALB physically adsorbed onto a macroporous acrylic polymer resin (Lewatit VP OC 1600, Bayer). Primarily, commercial uses of CALB are limited to production of high-priced specialty chemicals because of the high cost of commercially available CALB preparations Novozym 435 (Novozymes A/S) and Chirazyme (Roche Molecular Biochemicals). Studies to better correlate enzyme activity to support parameters will lead to improved catalysts that have acceptable price-performance characteristics for an expanded range of industrial processes. 

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