The Total Synthesis of Aromatic Steroids

Based on that methodology, Oppolzer [551] and Nicolaou [552] devised procedures for the total synthesis of aromatic steroids as (+)-estradiol and ( )-estra-l,3,5(10)-triene-17-one. In this latter case, experimental conditions for the pyrolytic step are given. 

This volume continues the series with chapters describing the reports and progress in the total synthesis of aromatic steroids, carbohydrates, genes, pyrrole pigments, and triterpenoids since the appearance of Volumes 1 and 2 some ten years ago. 

D. Taub, in J. A. Simon, ed., The Total Synthesis of Natural Products, Vol. 6, John Wiley Sons, Inc., New York, 1984, pp. 1—50 K. P. C. Vollhardt, Strategies and Tactics in Organic Synthesis, Academic Press, Inc., New York, 1984, pp. 299—324, for reviews on total synthesis of aromatic steroids. 

Naturally Occurring Aromatic Steroids" in The Total Synthesis of Natural Products vol, 2, J. ApSimon, Ed. (John Wiley Sons, New York, 1973) pp 642-663. 

Chem. Common. 1967, 1253 Marshall, Deghenghi, Can, J Chem. 47, 3127 (1969). Component of Conjugated Estrogenic Hormones, q.v. Review of synthetic studies Taub, "Naturally Occurring Aromatic Steroids in The Total Synthesis of Natural Products vol, 2, J. ApSimon, Ed. (John Wiley Sons. New York, 1973) pp 664-670,... 

This review covers the literature published during 1972-1981 and updates the chapter on the total synthesis of naturally occurring aromatic steroids that appeared in Volume 2 (pp. 641-725) of this series. 

Methods of Forming and Transforming the Rings. In the total synthesis of steroids, ring closure is carried out by very diverse methods the limits of applicability of which are shown in Table 4, These methods can be divided into three main groups cyclization with the participation of aromatic rings, with the participation of nonaromatic acids and esters, and with the participation of nonaromatic carbonyl compounds. 

In the majority of cases, all the features of the diene synthesis discussed above give fairly reliable grounds for determining the structure of the reaction products formed. When the correct use of these laws has been taken into account, it has been possible to achieve considerable success in the total synthesis of both aromatic and nonaromatic steroids. At the same time, of the theoretically possible routes for the construction of the steroid skeleton using the diene synthesis, only the type of synthesis AB — CD described in Chapter II can be regarded as comparatively well studied, while the majority of the possibilities of the diene synthesis in the steroid series remain practically unused, although the feasibility of many of them has been shown in model experiments. 

Intermolecular cyclopropanation of diazoketones is an effective method in organic synthesis. Wenkert and coworkers have applied this methodology to the synthesis of a substantial number of cyclopropane adducts 2868, 2969 and 307° which are synthetic intermediates in the preparation of natural products (equations 41—43). Copper catalysts were chosen for these transformations. Another interesting application of intermolecular cyclopropanation is to be found in Daniewski s total synthesis of an aromatic steroid. Palladium(II) acetate catalysed decomposition of 4-bromo-l-diazo-2-butanone in the presence of m-methoxystyrene was used to give the cyclopropyl ketone 31 which was a key intermediate in the total synthesis (equation 44)71. 

Removable cation-stabilizing auxiliaries have been investigated for polyene cyclizations. For example, a silyl-assisted carbocation cyclization has been used in an efficient total synthesis of lanosterol. Other conditions for the cyclization of polyenes and of ene-ynes to steroids have been investigated. Oxidative free-radical cyclizations of polyenes produce steroid nuclei with exquisite stereocontrol Besides the aforementioned A-ring aromatic steroids and contraceptive agents, partial synthesis from steroid raw materials has also accounted for the vast majority of industrial-scale steroid synthesis. 

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