Gyula Horváth

Microbial transformation of β-sitosterol and stigmasterol into 26-oxygenated derivatives

The genetically modified Mycobacterium sp. BCS 396 strain has been used to transform sterols with stigmastane side chain in order to obtain 26-oxidized metabolites. beta-Sitosterol (I) was transformed to 4-stigmasten-3-one (II), 26-hydroxy-4-stigmasten-3-one (III), and 3-oxo-4-stigmasten-26-oic acid (IV), while stigmasterol (V) was converted to 4,22-stigmastadien-3-one (VI), 6 beta-hydroxy-4,22-stigmastadien-3-one (VII), 26-hydroxy-4,22-stigmastadien-3-one (VIII), 3-oxo-4,22-stigmastadien-26-oic acid methyl ester (IX), and 3-oxo-1,4,22-stigmastatrien-26-oic acid methyl ester (X) with that strain. In both beta-sitosterol and stigmasterol, 26-oxidation generates the R-configuration on C-25.

Reinvestigation of the acetalation of d-glucitol with acetone-zinc chloride

Abstract The acetonation of d -glucitol in the presence of zinc chloride has been studied in detail by gas-liquid chromatographic techniques. From among the 12 different peaks, those belonging to the 1,2:3,4:5,6-tri-, 1,2:3,5:4,6-tri-, 3,4:5,6-di-, 2,3:5,6-di-,1,2:3,4-di-, 1,2:5,6-di-, 1,2:4,6-di-, 1,2-mono-, 2,3-mono-, 3,4-mono-, and 5,6-mono-acetals could be identified. The course of the reaction was also studied by g.l.c. From the time-dependent ratio of the different acetals, it could be concluded that the reaction is kinetically controlled at the beginning, when terminal acetals are mainly formed. In the thermodynamically controlled equilibrium, reached after 5 days, the 1,2:3,4:5,6-tri- and the 2,3:5,6-di-acetal are present in almost equal proportions. The structure of the (new) 1,2:3,5:4,6-triacetal was established by mass-spectrometric and 13 C-n.m.r. investigation.

Microbial hydroxylation of 13β-ethyl-4-gonene-3,17-dione

Abstract Among the microbiological transformations of steroids 15α-hydroxylation of 13β-ethyl-4-gonene-3,17-dione is an industrially important one [Von H. Hofmeister, K. Annen, H. Laurent, K. Petzoldt, R. Wiechert, Arzneim.-Forsch. 36 (1986) 781], since it results in an intermediate of the synthesis of Gestoden, a widely used contraceptive drug. The aim of our research was to select fungal strains for hydroxylation of 13β-ethyl-4-gonene-3,17-dione which produce the 15α-hydroxylated product in a high yield. According to our taxonomical studies, several species of Aspergillus, Fusarium, Mortierella, and Penicillium genera fulfill this requirement. It has been reported that the 15α-hydroxylating enzyme of Penicillium raistrickii is inducible by various steroidal compounds [S. Irrgang, D. Schlosser, H.-P. Schmauder, Biotechnol. Lett. 14 (1992) 33]. We found that the enzyme of Fusarium nivale (VJ-63 strain) is also advantageously induced by norethisterone, which significantly increased the economic efficiency of this biotransformation process [A. Jekkel, E. Ilkőy, J. Sutő, G. Ambrus, Gy. Horvath, I. Bősinger, I. Pallagi, I. Lang, E. Gyepessy, Hungarian Patent Appl. P-9602249 (1996)].

Novel 26-oxygenated products in microbial degradation of ergosterol

In order to investigate the effect of the different stereochemistry of C-24 on the microbial C-26 oxidation of sterol side-chain the genetically modified Mycobacterium sp. BCS 396 strain was used to transform erogsterol. Ergosterol was converted to 3-oxo-4,22-ergostadien-26-oic acid methyl ester, 3-oxo-1,4,22-ergostatrien-26-oic acid methyl ester, and 3-oxo-1,4,22-ergostatrien-26-oic acid, the structures of which have been determined by IR, 1H NMR, 13C NMR, and mass spectroscopy. The X-ray structure of 3-oxo-4,22-ergostadien-26-oic acid methyl ester revealed that oxidation at C-26 of the ergostane side-chain generates a chiral center with S-configuration at C-25 as a result of chiral induction of the C-24 center.

Novel intermediates of microbial side chain degradation of sitosterol

Abstract We describe the structure and stereochemistry of some new 26-oxygenated steroid derivatives obtained by microbial transformation of sitosterol.

The mass spectral fragmentation of 1,4-butanediol

The behaviour of 1,4-butanediol under electron impact at 70 and 12.5 eV has been studied with the aid of high resolution mass spectra. Based on metastable ion decompositions and deuterium labelling, mechanisms are proposed for the formation of the abundant ions of this compound.