Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing oxygen-containing organic compound
Patent
1996-04-08
1997-08-19
Witz, Jean C.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing oxygen-containing organic compound
435134, 435174, 435176, 435177, 435180, 435198, C12P 762
Patent
active
056587694
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a process of enzymatically preparing esters of carboxylic acids using a lipase.
It is known, for example from WO-A-8802775 (Novo Industri A/S) to use lipase in ester hydrolysis, ester synthesis and interesterification (acidolysis, alcoholysis, ester interchange) reactions, but all these reactions have been restricted to the use of primary and secondary alcohols.
In French Patent Specification FR-A-2,617,501 (Soc. Nat. Elf Aquitaine) it has even been proposed to carry out enzymatic reactions in tertiary alcohols, like t-butanol, or t-amyl alcohol, as a solvent, thus indicating that no reaction was expected to occur at all between this solvent and the substrate to be treated with the enzyme. This view is confirmed experimentally by S. Okumura et al. in Biochim. Biophys. Acta 575, 156-165 (1979) in which the ester synthesis by microbial lipases was investigated. None of the lipases of Aspergillus niger, Rhizopus delemar, Geotrichum candidum or Penicillum cyclopium was able to synthesize esters of tertiary alcohols, phenols or sugar alcohols (see especially Table I).
Porcine pancreatic lipase was found by A. Zaks and A. M. Klibanov to catalyse the alcoholysis reaction between tributyrin and various primary and secondary alcohols in a 99% organic medium (Science 224 (15 Jun. 1984) 1249-1251). It was found that dry lipase was completely inactive in the alcoholysis reaction with tertiary alcohols, but in Table I it has been indicated that the initial rate of the alcoholysis reaction between tributyrin and t-butanol catalysed by wet porcine pancreatic lipase (3.6 wt % water in the enzyme) is 22 .mu.mole/h per 100 mg of lipase. There is no indication, however, of any yields of product.
Finally, I. L. Gatfield has described (Lebensm.-Wiss. u.-Technol. 19 (1986) 87-88) the enzymatic synthesis of esters in non-aqueous heterogeneous systems under the influence of the lipase from Mucor miehei (ex Rapidase, Seclin, France). It was found that both primary and secondary aliphatic alcohols can be esterified efficiently, but not tertiary alcohols. In Table 1 t-butanol has been indicated to exhibit a degree of esterification with oleic acid (in equimolar quantities of acid and alcohol; using 3 wt % of the Mucor miehei enzyme; magnetic stirring in closed vessels at room temperature for 3 days) of 14%. A repetition of this experiment by applicants of the present application did not produce any t-butyl oleate, however, and it is assumed that the measured degree of esterification of 14% in fact relates to impurities (particularly secondary butanol) present in the t-butanol, since the detection technique used was based on titration, which does not differentiate between the individual ester species.
The absence of any acid numbers and ester values in this article does not allow any further conclusions, but in their German Patent Application DE-A-3,108,927 (referred to in the article) the inventors calculate the degree of conversion from the acid numbers and ester values, as is usual in this type of reactions, but although in this patent application also Mucor miehei lipase (Esterase 30,000; Trade Mark, ex Rapidase, Seclin, France) is used, the invention is clearly restricted to primary and secondary alcohols, which clearly speaks for the non-reactivity of the tertiary alcohols in this enzymatic reaction.
In the enzymatic ester synthesis from alcohols and acids it has up till now therefore thought to be impossible to synthesize esters in which the alcohol part is sterically hindered around the ester bond, i.e. esters derived from tertiary alcohols. The availability of such an enzymatic ester synthesis would be of value, however, particularly in the synthesis of "chemically clean" esters, in which no traces of any catalysts or side products are present and in which there is no danger of colour formation.
The present invention provides such an enzymatic process for preparing sterically hindered esters. It has been found that certain lipases, viz. those having hydrolytic activity with esters in which th
REFERENCES:
Aleksey Zaks et al: "Enzymatic catalysis in organic media at 100 C", Science, vol. 224, No. 4654, Jun. 15, 1984, pp. 1249-1251, cited in the applications, see abstract, see p. 1250, right column, paragraph 2; see p. 1251, left column, paragraph 2.
Brackenridge, et al: "Enzymatic resolution of oxalate esters of a tertiary alcohol using porcine pancreatic lipase", Journal of the Chemical Society, Perkin Transactions 1, No. 10, May 21, 1993, pp. 1093-1094, see p. 1093, left column, paragraph 1.
Heldt-Hansen et al: "A new immobilized positional nonspecific lipase for fat modification and ester synthesis", ACS Symposium Series, Biocatalysis In Agricultural Biotechnology, vol. 389, 1989, pp. 158-172, see abstract, see p. 158, para.1,-p. 159, para 1,-see p. 160, para. 4, -see p. 166, para. 2, -see p. 171, para. 1 -para. 4.
Bosley John Anthony
Casey John
Macrae Alasdair Robin
Mycock Gary
Unichem Chemie BV
Witz Jean C.
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