Preparative-scale bioconversion

The first exploitation of microbial BVase to produce chiral lactones from cyclic racemic bicyclo[2.2.1]hept-2-en-7-ones (Fig. 10) was reported by Ouazzani et al. [17]. A report of preparative scale bioconversion of cyclic ketone was made [26]. The preparative scale bioconversion of using Acinetobacter TD 63 provides lactones in high optical purity [27]. Subsequently [28], whole-cell bioconversions of bicyclic lactones was made, using Acinetobacter sp. NCIB 9871 and Pseudomonas sp. NCIB 9872 to produce file same chiral synthons. In all cases, the racemic ketone was oxidized, and equal amounts of the regioisomeric lactones (—)-(i5, 5/ )-2-oxabicyclo[3.3.0]oct-6-en-3-one and (—)-(iR,55)-3-oxabicyclo[3.3.0]oct-6-en-3-one were produced in high enantiomeric purity. 

For the screening, 25 microbial cultures, obtained from the University of Mississippi Department of Pharmacognosy culture collection, were used. Microbial bioconversion studies of sarcophine (45) showed that it can be metabolized by several fungi species. Preparative-scale fermentation with Absidia glauca American-type culture collection (ATCC) 22752, Rhizopus arrhizus ATCC 11145, and R. stolonifer ATCC 24795 resulted in the isolation... 

Microbial bioconversion studies of manzamine A and ent-8-hydroxymanzamine A have shown that they can be metabolized by several microbial species.76 Preparative-scale fermentation of manzamine A with Fusarium oxysporium f. gladioli ATCC 11137 resulted in the isolation of the known ircinal A (61) as a major metabolite. Preparative-scale fermentation of enf-8-hydroxymanzamine A with Nocardia sp. ATCC 11925 and Fusarium oxysporium ATCC 7601 resulted in the isolation of the new major metabolite 12,34-oxamanzamine F (62). The latter metabolite showed no cytotoxicity against different cell lines (>10 pg/ml). 

The bioconversions with these yeasts were performed on a preparative scale [4]. The yields and diastereomeric purities of the products and the molar ratios (Si5, C7 )-2a/(Si7 ,C5)-2a are listed in Table 1. 

Bioconversion of this compound with growing cells of Pichia pijperi (ATCC 20127) on a preparative scale [5] yielded a mixture of the l-sila-2-cyclohexanol (SiR,C5)-2a and the non-converted substrate (Si5,CfJ)-3a (Scheme 3). After chromatographic separation of these compounds... 

The oxidation of racemic fenchone by a Corynebacterium sp.[7<>1 (reclassified as Mycobacterium rhodochrous), an organism which grows at the expense of either (+)- or (-)- camphor, has also been reported. This was shown to lead, in a 45% yield, to a 90/10 mixture of 1,2 and 2,3-fencholides, as shown in Fig. 16.5-12. This result contrasts with the chemical oxidation of fenchone with peracetic acid, where 2,3-fencholide is the major product in a 40/60 mixture. Accumulation of these lactones is a priori surprising as compared with the total degradation of the structurally similar camphor substrate. However this may simply be due to the fact that this lactone, unlike that formed from camphor, is chemically stable in the medium. Of course, one has also to assume that, here again, the strain is devoid of any lactone hydrolase. This bioconversion was the first gram-scale preparative report... 

Pharma. Darmstadt, Germany) to give a stable eniyme preparation. Given the low solubility of (-) Carbovir, the concentration of (-)-2 was reduced to 2.5 g/iiter in bioconversions with immobilized enzyme so that the beads could easily be recovered from the reaction mixture without interf ence from the product. The enzyme was reused for up to 10 cycles without any significant loss of activity. This work demonstrated the potential of adenosine deaminase as a catalyst for large-scale production of optically pure (-)-cat-bovir. More recently, alternative routes to gain access to either enantiomer of carbovir have also been reported (40,41)-... 

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