Candida lactone

The nature of the product strongly depends on the length of the hydroxy acid generally when the hydroxyl group is remote the yield of lactone drops significantly. For example, 10-hydroxydecanoic acid [1679-53-4] does not produce any decanoUde instead, the reaction proceeds by intermolecular oligomerization, and a complex mixture of di-, tri-, tetra-, and pentalactones results (90). However, when Pseudomonas sp. or Candida iylindracea]i 2Lses are incubated with 16-hydroxyhexadecanoic acid [506-13-8] hexadecanoUde is the predorninant product (91). 

Lipase-catalyzed intermolecular condensation of diacids with diols results in a mixture of macrocycUc lactones and liuear oligomers. Interestingly, the reaction temperature has a strong effect on the product distribution. The condensation of a,(D-diacids with a,(D-dialcohols catalyzed by Candida glindracea or Pseudomonas sp. Upases leads to macrocycUc lactones at temperatures between 55 and 75°C (91), but at lower temperatures (<45°C) the formation of oligomeric esters predorninates. Optically active trimers and pentamers can be produced at room temperature by PPL or Chromobacterium viscosum Upase-catalyzed condensation of bis (2,2,2-trichloroethyl) (+)-3-meth5ladipate and 1,6-hexanediol (92). 

Various cyclic esters have been subjected to hpase-catalyzed ring-opening polymerization. Lipase catalyzed the ring-opening polymerization of 4- to 17-membered non-substituted lactones.In 1993, it was first demonstrated that medium-size lactones, 8-valerolactone (8-VL, six-membered) and e-caprolactone (e-CL, seven-membered), were polymerized by lipases derived from Candida cylindracea, Burkholderia cepacia (lipase BC), Pseudomonas fluorescens (lipase PF), and porcine pancreas (PPL). °... 

Since then, the process has been extended to a wide variety of lactones of different size and to several lipases, as recently reviewed [93-96]. Interestingly, large-membered lactones, which are very difficult to polymerize by usual anionic and coordination polymerizations due to the low ring strain, are successfully polymerized by enzymes. Among the different lipases available, that fi om Candida antarctica (lipase CA, CALB or Novozym 435) is the most widely used due to its high activity. An alcohol can purposely be added to the reaction medium to initiate the polymerization instead of water. The polymerization can be carried out in bulk, in organic solvents, in water, and in ionic liquids. Interestingly, Kobayashi and coworkers reported in 2001 the ROP of lactones by lipase CA in supercritical CO2... 

The biotechnological production of flavour compounds is particularly focused on esters and lactones. Lipase from Mucor miehei is the most widely studied fungal lipase [30-35]. Esters of acids from acetic acid to hexanoic acid and alcohols from methanol to hexanol, geraniol and citronellol have been synthesised using lipases from Mucor miehei, Aspergillus sp., Candida rugosa, Rhizopus arrhizus and Trichosporum fermentans [32-37]. 

Scheme 23.18 a De novo biosynthesis of coconut-like 6-pentyl-a-pyrone by Trichoderma sp. b Production of macrocyclic musk-like lactones by a combination of microbial co-hydroxylations and co-l-hydroxylations and subsequent chemical conversion steps, c Production of macrocyclic musk fragrances initiated by terminal oxidation of hydrocarbons with Candida tropicalis... 

Reduction of ketopantoic acid to D-pantoic acid (0, (4) in Fig. 8). Agrobacterium sp. S-246 is a good source of ketopantoic acid reductase. The yield of D-pantoic acid reached 119 g/1 (molar yield, 90% optical purity, 98% e.e.) on incubation with washed cells of the bacterium [102]. From a practical point of view, ketopantoic acid reduction with Agrobacterium cells has several advantages over ketopantoyl lactone reduction with Candida (or Rhodotorula) cells. The former results in a higher product yield, molar conversion and optical purity of the product than the latter. It is necessary to maintain the substrate level at lower than 3% in the case of the ketopantolactone reduction, but not for the ketopantoic acid reduction. 

While diketene remains a very important synthetic precursor, there has been increasing interest in the chemistry of a-methylene-/3-lactones, 3-methylene-2-oxetanones. However, unlike diketene, which can be readily synthesized by the dimerization of aldehydic ketenes, there are few methods for the synthesis of a-methylene-/3-lactones in the literature. Recent strategies for the preparation of the compounds are discussed in Section 2.05.9.2. The kinetic resolution of racemates of alkyl-substituted a-methylene-/3-lactones has been carried out via a lipase-catalyzed transesterification reaction with benzyl alcohol (Equation 21) <1997TA833>. The most efficient lipase tested for this reaction was CAL-B (from Candida antarctica), which selectively transesterifies the (A)-lactone. At 51% conversion, the (R)-f3-lactone, (R)-74, and (A)-/3-hydroxy ester, (S)-75, were formed in very high enantio-selectivities (up to 99% ee). 

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. 

Decalactone Ricinolic acid, cor-rolic acid, Massoia lactone or 11-hydroxy hexadecanoic acid Candida species, Clador-sporium sua-volens, baker s yeast Peach, buttery... 

Candida strains convert ricinoleic acid into If-decalactone, which displays the fatty, fruity aroma typical of peaches. Ricinoleic acid (12-hydroxy octadec-9-enoic acid) is the major fatty acid in castor oil (approx. 80 %). The yeast can lipolyze castor oil glycerides and the liberated ricinoleic acid is subsequently metabolized via d-oxidation and eventually converted to 4-hydroxy-decanoic acid (Figure 5). Recently a European patent has been filed (20) essentially covering the same procedure. Shake culture fermentations were carried out on 100 ml scale for one week. The 4-hydroxydecanoic acid formed was converted to )f-decalactone by boiling the crude, acidified (pH 1.5) fermentation broth for a period of 10 minutes. The lactone was isolated via solvent extraction and a yield of some 5 g/1 was obtained. The same lactone was detected as the major volatile component formed when the yeast, Sporobolomyces odorus was grown in standard culture medium (21). Although the culture medium displayed an intense fruity, typical peach-like odor, the concentration of y-decalactone amounted to no more than 0.5 mg/1. 

Nakaoki, T., Kalra, B., Kumar, A., Gross, R.A., Kirk, O., and Christensen, M. (2002) Candida antarctica lipase B catalyzed polymerization of lactones Effect of immobilization matrix on polymerization kinetics and molecular weight. Abstracts of Papers of the Am. Chem. Soc., 224, U473. 

Table 11.1-13. Lipase-catalyzed enantiomer-differentiating hydrolysis of racemic carboxylic acid esters and lactones in aqueous solution (PPL pig pancreas lipase, PSL Pseudomonas sp lipase, PFL Pseudomonasfluorescens lipase, CCL Candida cylindracea lipase, ANL Aspergillus niger lipase, PCL Pseudomonas cepacia lipase, CAL-A Candida antarctica A lipase, CRL Candida rugosa lipase, CAL Candida antarctica lipase, not specified).

The usefulness of lipases for the enantiomer-differentiating hydrolysis of carboxylic acid esters and lactones is impressively demonstrated by examples 1-S9 of Table 11.1-13. This broad substrate spectrum is covered mainly by lipases from Candida cylindracea (rugosa), pig pancreas and several Pseudomonas sp. lipases. Carboxylic acid esters having the alkoxycarbonyl group attached to a secondary, tertiary or even quaternary carbon atom are substrates. Thus, in contrast to... 

The two a-amino acids 48 and 49 with unprotected amino groups are hydrolyzed with high enantioselectivity. The series of methyl-substituted seven-membered lactones 52-55 (Table 11.1-13) are converted in the presence of Candida antarctica lipase yielding the slow-reacting lactones with ee values between 72 and 94%. 

Baeyer-Villiger oxidation. 30% Hydrogen peroxide in acetic acid is able to oxidize cyclobutanones to the y-lactones. In the presence of myristic acid and immobilized Candida antarctica lipase" other ketones also undergo Baeyer-Villiger oxidation with HaOj. 

D-Pantoyl lactone Carbonyl reductase (Candida parapsilosis) 350 (100)... 

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