G. Spassov

Synthesis of galanthamine and related alkaloids - new approaches. I.

Abstract Modifications of protecting groups and of the oxidative coupling conditions lead to pure crystalline intermediates in the synthesis of galanthamine derivatives and gave dienone A in better yields than reported before. The E -configuration of amide 3′ in crystalline state has been determined by X-ray diffraction. Streptomyces affinis 6737 reduces A to the optically active (−)-epigalanthamine derivative C, whose absolute configuration was determined by Bijvoets method. Nematospora corylii CBS 2608 reduces to racemic B. With Ashbya gossypii IFO 1355 a mixture of racemic B and optically active C is obtained. some other microbial transformations are described.

4-hydroxymethyl-quinoline from Polyporus species

Abstract 4-Hydroxymethylquinoline was isolated from Polyporus versicolor and P. sanguineus .

Crystallographic monitoring of microbiological steroid transformations

SummaryProduct crystal formation has been observed for the transformation of pregnenolone triacetate to Reichstein-S-17α-acetate with Flavobacterium dehydrogenans ATCC 13930 at a concentration of 20 g/l, and for the conversion of hydrocortisone-17α-acetate to prednisolone-17α-acetate with Arthrobacter simplex ATCC 6946 (2 g/l). Hydrocortisone-17α-acetate was obtained from pregnenolone triacetate by a two-stage fermentation with F. dehydrogenans and Curvularia lunata NRRL 2380. At the concentration used (1 g/l) for the second stage, crystal formation of hydrocortisone-17α-acetate could not be observed. It was demonstrated that the progress of the first stage of the transformation may be studied by the powder diffraction technique. Crystal data and structures have been determined for five of the steroids involved in the above conversions.

Transformation of microcrystalline hydrocortisone by free and immobilized cells of Arthrobacter simplex

SummaryThe transformation of microcrystalline hydrocortisone by free and immobilized cells of Arthrobacter simplex resulted in formation of prednisolone. The effect of medium composition, non-ionogenic surfactants and exogeneous electron acceptors on the Δ1-dexydrogenase activity of free and immobilized cells is described.

Biotransformations of alkaloids: A challenge

The biotransformation of various alkaloids is reviewed. Special attention is paid to problems in microbial transformations and the different solutions offered by different authors. The biosynthetic potential of the strains selected for biotransformations is compared to the reaction observed in microbal oxidation. An outlook to future developments in other areas, especially from active site modelling, genomics and microbial ecology, are discussed which may contribute to problems in biotransformations.

Conversion of d-sorbit to l-sorbose by cells of Acetobacter suboxydans immobilized in sintered glass

A simple method for immobilizing cells of Acetobacter suboxydans by adsorption on inorganic sintered glass carriers is described. The immobilized cell preparations exhibited 100% of the initial activity when converting d-sorbit to l-sorbose. This sintered glass was used in a fixed-bed loop reactor with a working volume of 0.2 l for semicontinuous and continuous experiments. A prolonged working life span was achieved, which could possibly satisfy requirements for scaled-up operations.

Conversion of corticosteroid hormones by immobilized cells of Flavobacterium dehydrogenans, Curvularia lunata and Arthrobacter simplex on ceramic carriers

Abstract Different possibilities for converting pregnenolone triacetate to prednisolone using immobilized preparations of Flavobacterium dehydrogenans, Curvularia lunata and Arthrobacter simpelex in a fixed-bed loop reactor were investigated. The effects of the carrier, substrate concentration, pH and temperature on the rate of the substrate conversion were studied also. The biotransformations were performed with a continuous or semicontinuous substrate supply. A convenient pathway for the formation of prednisolone is proposed on the basis of the results obtained.

Stereoselective reduction of substituted benzophenones by microorganisms I.

Abstract Debaryomyces marama enantioselectively reduces p-Cl-benzophenone to the S-alcohol with high enantiomeric excess.

Microbial transformations of galanthamin-precursors

SummaryGalanthamin is a medical important alkaloid. Its chemical synthesis gives a racemic product in low yields. Starting with a belladinderivative an enzymatic ring closure should lead exclusively to a chiral product possibly with the native structure. Although this reactions type is unknown in preparative biotransformations a large number of microorganisms were tested, unfortunately without success. On the other hand in the screen transformation products were found resulting from specific dealkylations of the subtrate. The type of metabolite formed was dependent on the fungi utilized for the transformation. Additionally two N-oxides were formed by Septomyxa affinis, one in good yield. It is possible that the chirality of this compound can direct the ring closure preferentially or exclusively to the desired stereoisomer of narwedine.

Effect of matrix on (S)-p-chlorodiphenylmethanol production by immobilized Debaryomyces marama

The product (S)-p-chlorodiphenylmethanol is obtained through stereoselective reduction of p-chlorobenzophenone using Debaryomyces marama cells, immobilized on Raschig rings. This process involved continuous fermentations in bioreactors for a period of 10 days. The conversion was 86% with a volumetric productivity of 0.248 litre−1 d−1. Comparative experiments with D. marama cells, incorporated in alginate, k-carrageenan or agar–agar gels were also performed. These results demonstrated superiority of the immobilization on ceramic carriers compared to other methods. Passive immobilization of D. marama cells on ceramic carriers has many advantages in comparison with gel-incorporation of the cells. For example, during a long bioreactor run, only a limited amount of cells could remain incorporated within the gel. Therefore immobilized cell preparations will be a convenient methodology in the production of optically active compounds such as pharmaceutical drugs.