Totalsynthese von natürlichem östradiolmethyläther

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

“…As illustrated by several historic milestones, significant progress has been made in the formation of quaternary carbon stereocenters in cyclic systems. For example, the very first enantioselective transformation of an achiral starting material to form a quaternary carbon stereocenter was reported in 1966 by chemists at Schering AG through the desymmetrization of the indicated cyclopentanedione via biocatalytic reduction (Scheme , top) . A related desymmetrization to form a quaternary carbon stereocenter is represented by the Hajos–Parrish–Eder–Sauer–Wiechert reaction, which was reported shortly thereafter (Scheme , middle). , Subsequent to these pioneering efforts, numerous methods for the asymmetric synthesis of stereogenic quaternary carbon centers were reported in the literature, including methods beyond desymmetrization.…”

Designing Total Syntheses

“…Only cZ-159 reacted, and the newly formed cZ-21-hydroxy-159 was separated from unreacted Z-159 [127]. Similarly, androstenedione has been resolved with Saccharomyces cerevisae (17-carbonyl reduction) [112], 160 with Pseudomonas testosteroni (oxidation of hydroxyl) [128], 161 (R = 0 ) with Saccharomyces cerevisiae (17-carbonyl reduction) [129], 162 (R = 0 , R' = a-H,|8-OH) with Saccharomyces uvarum (keto reduction) [130], 162 (R = -OH, -H, R' = 0 ) with Bacillus thuringiensis [130], 163 and 160acetate with protaminase (hydrolysis of acetate) [129], D-homo-162 (R = R' = 0 ) with Saacharomyces carisbergensis (14-and 17a-carbonyl reduction) [131], estradiol with placental 17/?-hydroxysteroid dehydrogenase [132], 164 with Rhizopus arrhizus [133], 165 (R = Et or n-Pr, R /= =H; R = R' = Et) with Corynebacterium simplex [134], and 166 with a Racemic 167 was resolved with Arthrobacter simplex, which contains a steroid 1,2-dehydrogenase. Similar resolution of 168 (with A-ring aromatization) and 169 helped to define the stereo requirement of the enzyme for an R configuration at C-10.…”

Steroidal estrogens

“…Bellet, Nominé, and Mathieu have recently reported (34) the microbiological reduction of the intermediate trione XLI to the optically active cyclopentanolone (XLIII) in 70% yield. This makes possible the total synthesis of natural estrone (I) without loss of an enantiomer at a later stage (see also ref 151).…”