Totalsynthese optisch aktiver Steroide, I. Mikrobiologische stereospezifische Reduktion von 3‐Methoxy‐8.14‐seco‐1.3.5(10).9‐östratetraen‐14.17‐dion

Abstract

3-Methoxy-8.14-seco-l.3.5( 10).9-ostratetraen-l4.17-dion (l), ein Zwischenprodukt zur Darstellung von racem. &tradiol-3-methylather, wurde mikrobiologisch zum optisch aktiven 14cr-ol-17-on (3) bzw. 17/3-ol-14-on (6) reduziert. Diese Substanzen ermoglichen die Totaisynthese von optisch aktiven Ostranderivaten ohne Racemattrennung.

Stereoselective Reduction of Prochiral Cyclic 1,3-Diketones Using Different Biocatalysts

“…The results obtained using compound 5 as substrate led us to perform the biotransformations of the other 2,2-disubstituted 1,3-cycloalkanediones using an initial substrate concentration of 28 mM (Table 2). 14c) 40 (20) the consumption of the (2R,3S)-stereoisomers and thus final accumulation of (2S, 3S)-13c and (2S, 3S)-14c.…”

“…Different 2,2disubstituted 1,3-cycloalkanediones were reduced using Saccharomyces cerevisiae giving good yields and sometimes excellent stereoselectivity, with formation, in all the cases, of the stereoisomers having (S)-configuration at the carbon bearing the hydroxy group [18,19]. An example of industrial relevant application of this type of stereoselectivity is offered by the reduction of ethyl secodione, which can be enzymatically reduced to (13R,17S)-ethyl secol, applied for the synthesis of contraceptive hormones [20,21].…”

Yeast‐Mediated Stereoselective Synthesis

“…A series of 2,2-disubstituted cyclopentane-1,3-diketones 43 ( Figure 21.13) has been reduced, and by monoreduction the products 44 and 45 were obtained in 9-75% yield with high diastereoselectivity [183][184][185][186][187][188]. Synthesis of nitro-substituted alkanes, alkenes, and aromatic compounds.…”

Directed evolution of an alcohol dehydrogenase for the desymmetric reduction of 2,2-disubstituted cyclopenta-1,3-diones by enzymatic hydrogen transfer

“…Chiral 2,2-disubstitued 3-hydroxycyclopentanones with an all-carbon quaternary chiral centre are valuable intermediates for the stereoselective synthesis of biologically important compounds. A few examples are estrone methyl ether, 1 cortistatins A and J, 2–3 aplysiasecosterol A, 4 cyathane terpenoids, 5 hamigerans, 6 gestodene and levonorgestrel. 7 The desymmetric reduction of prochiral cyclic 1,3-diketones is a straightforward approach to prepare these chiral cyclic hydroxyketones.…”

“…1 H NMR (400 MHz, CDCl 3 ) δ 4.19 (t, J = 6.8 Hz, 1H), 2.53-2.40 (m, 3H), 2.31-2.14 (m, 2H), 2.14-1.968 (m, 2H), 1.92-1.73 (m, 3H), 1.02 (s, 3H).…”