R. Vlahov

Synthesis of 9α-hydroxysteroids by a Rhodococcus sp.

Abstract 9α-Hydroxylation of Δ5-3β-hydroxysteroids (of androstane, pregnane, 24-nor- and 21,24-bisnorcholane groups) was carried out by a Rhodococcus sp. , isolated from a petroleum-containing soil sample. A large number of the investigated steroids was transformed into 9α-hydroxy-Δ4-3-ketones in satisfactory yields (50–90%) at high initial concentrations of the substrates (0.5–5.0 g/L). The influence of some structural features of the steroid molecule on the progress and effectiveness of the microbial transformation was also shown.

Synthesis of galanthamine: Intramolecular para-ortho-coupling of diaryl ethers by anodic oxidation.

Abstract Intramolecular para-ortho-coupling of the amide 4 to 7 was achieved by anodic oxidation in acetonitrile solution (containing 2% of methanol) in eighty % yield.

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.

Microbiological dehydrogenation of polyfunctional Δ5-3β-acetoxy steroids by Corynebacterium mediolanum strain B-964

SummaryA high-yield microbiological transformation of polyfunctional Δ5-3β-acetoxy steroids, containing an additional ring E, by Corynebacterium mediolanum strain B-964 was carried out, resulting in the corresponding Δ4-3-ketones. It was shown that the type of transformation and the yield of the reaction depend on the degree of saturation of the ring E and on the position of the oxygen-containing substituents in it.

Long-acting contraceptive agents: Aliphatic and alicyclic carboxylic esters of levonorgestrel

Esters of levonorgestrel (13 beta-ethyl-17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one) with a variety of aliphatic and alicyclic carboxylic acids have been prepared and characterised. In tests for the suppression of estrus in rats, esters with short-chain aliphatic acids and with cyclobutane-carboxylic acid were considerably more active than the standard, norethisterone enanthate (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one). Such esters show great promise for development as long-acting progestogens.

Stereoselective reduction of substituted benzophenones by microorganisms I.

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

A NEW SYNTHESIS OF ROXATIDINE ACETATE

Abstract A new four-step synthesis of N-{3-[3-(l-piperidinylmethyl)-phenoxy]propyl}acetoxyacetamide hydrochloride has been performed. The key aralkyl ether was synthesized in high yield under moderate conditions. A suitable scaling up permits a bulky production of the drug in 98.5% purity.

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.

Long-acting contraceptive agents: norethisterone esters of polyunsaturated acids

Some new derivatives of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) are described in which the 17 beta-hydroxyl group of the steroid is esterified with polyunsaturated aliphatic acids. The potential of these compounds as long-acting contraceptive agents has been evaluated.

Long-acting contraceptive agents: Cyclopropyl and cyclobutyl esters of norethisterone

Several esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) with carboxylic acids containing a cyclopropyl or cyclobutyl ring have been synthesized and the stereochemistries of the side-chains determined.