Hydroxyquinidine, the major metabolite of the Cinchona alkaloid quinidine, vvas prepared by synthetic chemical modification or microbial oxidation of quinidine. The structure of this metabolite has been demonstrated to be (3S)-3-hydroxyquinidine by 'H and 13C NMR, IR, UV and mass spectral analysis. Previously published comparisons of the 13C N M R spectra of 3-hydroxyquinidine and model compounds were used to establish the absolute stereochemistry of the metabolite (see ref. 8). This assignment has been verified by single-crystal X-ray analysis of ( 3 s ) -3hydroxyquinidine methanesulphonate. The gas-and solution-phase conformational preference of the metabolite derived from molecular modelling and NOE studies are compared with the conformation observed by X-ray crystallography.

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Microbiological and Enzymatic Transformations in the Synthesis of Prostacyclin Analogues For the synthesis of prostacyclin analogues, enzymatic and microbiological transformations are described leading to homochiral bicyclooctane building units.

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Several derivatives of the highly active aldosterone antagonists dihydrospirorenone (2) and spirorenone (3) were synthesized. The purpose of these efforts was to prepare compounds exhibiting reduced endocrinological properties with the same or better aldosterone antagonistic activity than that of spirorenone. The 1 alpha,2 alpha-methylene derivative 20 has a similar aldosterone antagonistic potency compared to that of spirorenone but does not show decreased endocrinological side effects. Other substituents as in compounds 4-11, 15-19, and 21 sharply decreased the aldosterone antagonistic activity of 2 or 3, respectively.