Investigation of enantioselective hydrolyses with fungal hydrolase systems
Growing cultures of fungi, chiefly of the genus Aspergillus, have been used to resolve some carboxylic acid esters.
The fungus Aspergillus carbonarius (ATCC 1025) has been employed to resolve racemic methyl jasmonate into its two major isomers [1S,2S(Z)]-(+)-methyl jasmonate, and the naturally abundant [1_R,2R(Z) ]-(-)-methyl jasmonate, with an enantiomeric excess of around 80%.
Studies into the induction of specific enzymes in Aspergilli, coupled with experiments on isolated enzymes suggest that the enzyme responsible for hydrolysis of methyl jasmonate is not a simple lipase.
Studies into the hydrolysis of molecules related in structure to methyl jasmonate, eg. methyl cucurbate, 2- (pent-2-enyl)cyclopentaneacetic acid methyl ester, 3- oxocyclopentaneaceticacid methyl ester, and various 2- substituted derivatives suggest that all the functionalities are important to enantioselectivity.
Studies into the hydrolysis of 2 diastereomers of methyl cucurbate, suggest that more than one hydrolytic enzyme is at work in Aspergilli.
Experiments into the hydrolysis of compounds unrelated structurally to methyl jasmonate, eg. 2-aryl and 2-phenoxypropanoicacid esters have also been performed. Aspergillus carbonarius (ATCC 1025) will hydrolyse the R- (-)- isomer of 2-phenylpropanoic acid methyl ester, in about 70% enantiomeric excess. The studies on non- jasminoid structures support the suggestion that more than one hydrolase is present.
In general it is found that the intact fungal cells are more enantiospecific than isolated enzymes. It is also found that the fungi used, hydrolyse the opposite isomer to that hydrolysed by procaryotic mycobacteria.
The potential for using both enantiomers of jasmonate as chiral building blocks has also been investigated. Racemic methyl jasmonate, protected as the 3-ketal, has been subjected to a variety of simple reactions including ozonolysis of the double bond, reduction of the methyl ester, and protection as the tosylate. The resulting molecules are 1,2,3-trisubstituted cyclopentanoids, each substituent being capable of further modification to produce cyclopentanoid natural products, eg. the prostaglandins, sarkomycin, homosarkomycin, and key intermediates en route to steroid D-rings. It is suggested that if resolved jasmonate were used, then these products could be prepared optically pure.
Rights holder© Simon Kerry
NotesA Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University.
EThOS Persistent IDuk.bl.ethos.329713
This submission includes a signed certificate in addition to the thesis file(s)
- I have submitted a signed certificate