| Popis: |
THE pioneering work of Sir Robert Robinson in the total synthesis of steroids, and his cycloaddition method,’ have proved most useful during the last 30 years and as a result a great number of syntheses of academic interest have been developed.2 Nevertheleas, only a single totally synthetic approach has led to the direct preparation on an industrial scale of optically active steroids belonging to the naturally occurring series.3a4 On the other hand, since the notorious studies of Pincuss on ovulation inhibition by compounds such as nor-ethindrone and nor-ethynodrel, the use of steroidal contraceptives has greatly increased. Today, several million women make use of 19-norsteroids to control their fertility and the preparative probIem of such compounds has become very important on account of the enormous potential of future users and the possible limitation of natural raw materials. Doubtless, since the first preparation of nor-testosterone through Birch’s reduction of aromatic rings,6 important progress has been made based on proximity attacks of carbon 19, starting either from diosgenin,’ or cholesterol.8 But these semi-synthetic approaches requiring elimination of the angular methyl group have considerable disadvantages when compared with the preparative schemes now described for 19-norsteroids in which these derivatives precede the ICI-methylated structures. A. The total synthesis recently developed is based upon the fundamental necessity of performing an early resolution, which opens the way, starting from common optically active intermediates, to a whole series of new compounds having the cotiguration of natural steroids. (a) The first synthesis on a large scale,9 starting from methoxytetralone, 1, led to a tricyclic intermediate, 2, which was resolved via its carboxylic group. From this stage |
