Progesterone, total synthesis

In general, the homo radical domino reaction is a powerful tool for the construction of complex molecules. Further examples are the synthesis of the BCD-Ring system of progesterone by Takahashi et al.,[521 the construction of bicyclic octanol derivatives by Sonoda et al.[531 and the total synthesis of (+)-claantholide and (-)-estafiatin by Lee et al.[541... 

A recent compound in this class, asoprinosil (29-9), is a more selective antagonist of progesterone and also shows reduced binding to glucocorticoid receptors. Treatment of the diene (29-1), a total-synthesis product-derived 19-nor gonane, with hydrogen peroxide results in selective reaction at the 5,10 double bond to... 

The First Total Synthesis of Progesterone Receptor Ligands, PF1092A, B and C... 

The synthesis of the female sex hormone progesterone by W. S. Johnson and co-workers at Stanford University is considered one of the classics in total synthesis. The last six-membered ring needed in the steroid skeleton was prepared by a two-step sequence using an intramolecular aldol reaction, as shown in Figure 24.5. 

This reduction-alkylation sequence has been extensively used in the total synthesis of natural products, such as progesterone and lupeol (Scheme... 

Progesterone, a female sex hormone, has been prepared by total synthesis and by modifications of other steroids. Using established methodologies, such as Diels-Alder cycloadditions, Michael additions, Robinson annulations, aldol reactions, and ring contraction reactions, propose a total synthesis of progesterone. Discuss the merits of your approach in comparison with the total synthesis reported by Woodward, R. B., Sondheimer, R, Taub, D., Heusler, K., McLamore, W. M. J. Am. Chem. Soc. 1952, 74, 4223. 

Johnson, W.S. et al. 1977, Asymmetric total synthesis of 1 la-hydroxy progesterone via a biomimetic polyene cyclization , Journal of the American Chemical Society, 99, 8341-3. 

A series of studies were conducted to develop new tactics for conducting polyolefin cyclizations. New initiating groups, solvents and acid promotors were examined. For example, acetal 80 was efficiently converted to 82, whose tricyclic structure resembles the ABC-ring system of the steroids, presumably via an intermediate cation of type 81 (Steroids-16). Advances of this type set the stage for the total synthesis of steroids via polyolefin cyclizations. We will focus largely on progesterone (see Steroids-1 or Steroids-19 for structure). 

Natural progesterone, A -pregnene-3,20-dione, has the structure expressed by formula (296). Its antipode (297, 298) must be named by the existing rules of nomenclature as "8a, 9)8,10j3,13a, 14jS,17Q -A -pregnene-3,20-dione. This name is not only difficult to understand but it is completely unsuitable for use since no name is left for the racemic compound it can be described only by a combination of the names of the two enantiomers. Consequently, it is natural that with the development of work on the total synthesis of steroids much attention has been devoted to the question of nomenclature. 

The application of nonenzymic biogenetic-like olefinic cyclizations for the stereospecific construction of polycyclic systems, developed by W. S. Johnson and his school, represents an exciting new approach to steroid total synthesis. The synthesis of progesterone, outlined below, is based on the finding that an appositely placed acetylenic bond participates in polyolefinic cyclizations directly to produce the C/D trans-fused hydrindane system... 

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