Asymmetric induction steroid synthesis

In the synthesis of steroid precursors containing a C 5 ethylated side chain, the rearrangement of allylic alcohol 5 via Eschenmoser rearrangement involves both relative and internal asymmetric induction yielding all possible diastereomers459-460. 

A most impressive exam e of catalytic asymmetric synthesis forms the basis for still another and very efficient approach to 19-norsteroids (10,11). The exact mechanism responsible for the extremely high asymmetric induction noted in the crucial conversion of prochiral to ketol 11 and ( )-enedione 12 still needs to be clarified (12,13). Nonetheless, these tftlral aldol products serve very effectively as steroid CD-ring synthons (8,14-21). 

Asymmetric induction (See also Enantioselective) chiral ketones, 62, 106-107 chiral sulfoxides, 8-9 steroid synthesis, 27, 278-281 Asymmetric syntheses. See Enantioselective. .. Asymmetry of vesicle membranes, 351 dATP. See 2 -Deoxynucleoside 5 -triphosphates Atropisomers binap chelands, 102-103 Kemp s acid arylimides, 347 porphyrin oligomers, 348—349 5,10,15,20-tetraarylporphyrins, 253 Axial/equatorial stereoselectivity ... 

Steroid Synthesis. -The challenge of total synthesis has produced further new solutions. A series of papers reports an interesting new approach to the steroid nucleus and illustrates its versatility. An early asymmetric induction plays an important part in this route. A new bis-annelation procedure has been applied to a synthesis of D-homo-oestrone. The carbon atoms of rings a and b are supplied by 6-viny -a-picoline which contains in a masked form the functionality necessary for annelation. 

In contrast, Michael additions of a,a-disubstituted lithium enolates proceed, apparently via the chelated form of enone sulfoxides (Figure 5.2), with almost complete jt-facial diastereoselectivity [104]. This methodology has been used in the asymmetric synthesis of the pheromone, (-)-methyl jasmonate (121), from cyclopentenone sulfoxide (98b) [105] via the intermediate (120), which was formed in at least 98% enantiomeric purity upon asymmetric Michael addition of bis a-silylated a-lithioacetate to (98b). Addition of the a-bromo enolate (122) to enantiomerically pure (98a) and oxidation gives the product sulfone (123), with almost complete asymmetric -induction with respect to the sulfoxide. Sulfone (123) was then converted into the steroidal sex hormone, (+)-oestradiol (124) (Scheme 5.42) [106]. 

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]. ... 

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. 

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