Asymmetric epoxidation steroids

This procedure was used for the asymmetric total synthesis of the steroid (+)-equilenin (7-7) [3]. Cyclopropylidene derivates 7-4 could be converted into the cyclobutanones 7-5 in good yields by applying an asymmetric epoxidation using the chiral (salen)Mnm complex 7-6 (Scheme 7.2) [4]. It is of interest that the demethoxy-lated substrate 7-4b led to 7-5b with a very high enantiomeric excess of 93%, whereas 7-4a gave 7-5a with only 78% ee. 

Recent syntheses of steroids apply efficient strategies in which open-chain or monocyclic educts with appropiate side-chains are stereoselectively cyclized in one step to a tri- or tetracyclic steroid precursor. These procedures mimic the biochemical synthesis scheme where acyclic, achiral squalene is first oxidized to a 2,3-epoxide containing one chiral carbon atom and then enzymatically cyclized to lanostetol with no less than seven asymmetric centres (W.S. Johnson, 1%8, 1976 E.E. van Tamden, 1968). 

A final example of the kind of specificity exhibited by enzymes is provided by squalene oxidocyclase. As shown in Fig. 4.65, this enz)nne catalyzes the conversion of the 30-carbon isoprene derivative squalene 2,3-epoxide, which contains only one asymmetric carbon atom, to the steroid lanosterol in a single step that forms four new carbon-carbon bonds and seven new chiral centres in 100% yield and with no isomeric impurities. 

The natural occurrence of 24,25- and 25,26-dihydroxyvitamin D metabolites has led to studies of their synthesis and configurational assignment via the initial preparation of the correspondingly substituted cholesterol derivatives. Initial approaches to these compounds were carried out on oxidized forms of A24- or A25-steroids (98, 142, 154, 155, 169, 170) or by reduction of the ketol (46) (5i). In these cases, almost equal amounts of the diasteroisomeric epoxides or diols were obtained because the newly formed asymmetric position was too distant from a chiral center (i. e., at C-17 or C-20) for stereoselective induction. 

In a continuation of some elegant studies on the synthesis of sterols, the non-enzymic cyclization of the monosubstituted epoxide (200) has been achieved, using boron trifluoride. Although the process occurs in very low yield, it does generate four rings and seven asymmetric centres, all possessing the relative configuration of non-aromatic steroids ... 

Other reactions described, with varying degrees of success, have been chiral epoxidation, chiral hydrogenation, chiral iodination, and chiral reduction of keto-groups. One of the last reactions is especially interesting in using a chiral phase-transfer catalyst. Finally, Johnson and his co-workers have reported in full the asymmetric induction in their steroid synthesis via polyene cyclization [e.g. (46) (47) with ca. 90 % optical purity]. ... 

---