Aspergillus melleus

Biocatalysis has emerged as an important tool for the enantioselective synthesis of chiral pharmaceutical intermediates and several review articles have been published in recent years [133-137]. For example, quinuclidinol is a common pharmacophore of neuromodulators acting on muscarinic receptors (Figure 6.50). (JJ)-Quinudidin-3-ol was prepared via Aspergillus melleus protease-mediated enantioselective hydrolysis of the racemic butyrate [54,138]. Calcium hydroxide served as a scavenger of butyric acid to prevent enzyme inhibition and the unwanted (R) enantiomer was racemized over Raney Co under hydrogen for recycling. 

Application of NMR has been made to a restricted range of chlorinated aromatic compounds (Kolehmainen et al. 1992), and has been used to establish the source of oxygen in the metabolites produced from acetate and 02 by Aspergillus melleus (Staunton and Sutkowski 1991). 

Staunton J, AC Sutkowski (1991) NMR in biosynthetic studies aspyrone, asperolactone isoasperoloac-tone, metabolites of Aspergillus melleus. J Chem Soc Chem Commun 1106-1108. 

Transition metal catalysts and biocatalysts can be combined in tandem in very effective ways as shown by the following example (Scheme 2.21). An immobilized rhodium complex-catalyzed hydrogenahon of 46 was followed by enzymatic hydrolysis of the amide and ester groups of 47 to afford alanine (S)-9 in high conversion and enanhomeric excess. Removal of the hydrogenation catalyst by filtration prior to addition of enzyme led to improved yields when porcine kidney acylase 1 was used, although the acylase from Aspergillus melleus was unaffected by residual catalyst [23]. 

Highly active in reversing inhibition by albomycin-ferrimycin type antibiotics. Phenol-chloroform extraction of 201 of Aspergillus melleus culture followed by further purification yields 4.65 g of substance. Also produced by A. terreus (63). 

Similar labelling studies on aspyrone (27), a metabolite of Aspergillus melleus, gave the labelling pattern shown in Scheme 10 [24] which suggested that its bio-... 

Fig. 7 a,b. a- H Isotope induced shifts observed in the 100.6 MHz NMR spectra of aspyrone (27) enriched from feeding [2- C,2H3]acetate to Aspergillus melleus a with simultaneous... 

Acylases have also been applied to the kinetic resolution of amines. Aminoacylase I from Aspergillus melleus was used for the resolution of a range of arylalkylamines and amino alcohols via acylation with methyl 2 methoxyacetate (Figure 14.13) [19]. Excellent chemoselectivity was also observed in all cases, as the amino group was preferentially acylated in the presence of a primary alcohol functionality. However, poor to moderate enantioselectivity was observed, with values <10. The best result (E = 9.3) was obtained with 1 aminoindane 10 during the conversion to ester 38. 

The rearrangement of carbon chains with the extrusion of a carbon atom has been identified in several other biosyntheses. An example is provided by aspyrone (4.52) and asperlactone (4.53), which are metabohtes of Aspergillus melleus. The labelling pattern from [l,2- C2]acetate and from individually... 

Garson and J. Staunton, J. Chem. Soc., Perkin Trans. 1, 1981, 2577. Biosynthesis of fungal metabolites, asperlactone and its relationship to other metabolites of Aspergillus melleus, R.G. Brereton, M.J. Garson and J. Staunton, J. Chem. Soc., Perkin Trans. 1, 1984, 1027. 

Protease Origin Aspergillus melleus Amano Protease DS Industrial... 

Deaminase Origin Aspergillus melleus Amano Deamizyme 50000... 

ROH, Aspergillus melleus (enantioselective) ROH, Aspergillus niger (enantioselective)... 

L-Amino acid acylase from Aspergillus melleus (Amano acylase 30000) was used to hydrolyze racemic 6-acetoxybuspirone to (5)-6-hydroxybuspirone 2 in 96% enantiomeric excess (EE) after 46% conversion. The remaining (l )-6-acetoxy-buspirone with 84% EE was converted to (l )-6-hydroxybuspirone 2 by acid hydrolysis [28]. The EE of both enantiomers could be improved to more than 99% by crystallization as a metastable polymorph. Direct hydroxylation of buspirone to (5 )-6-hydroxbuspirone by Streptomyces antibioticus ATCC 14980 has also been described [28]. 

Hill, A.M., A. Jacobs, and J. Staunton Investigation of the Stereochemistry of the Tri- and Tetra-ketide Hydroxyacyl Intermediates in the Biosynthesis of the Polyketide Aspyrone in Aspergillus melleus using Deuterium Labelling and Deuterium NMR Spectroscopy. Chem. Commun. 859 (1995). 

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