Polycyclic systems steroid synthesis

In polycyclic systems the Birch reduction of C—C double bonds is also highly stereoselective, e.g. in the synthesis of the thermodynamically favored trans-fused steroidal skeletons (see p. 104 and p. 278). 

It is worth noting that in this synthesis of Cecropia juvenile hormone a strategy which is the reverse of the one developed by W.S. Johnson [8] for the synthesis of steroids and other fused polycyclic systems bearing cyclohexane rings is used. This method involves a non-enzymatic cyclisation of a polyunsaturated intermediate with the appropriate stereochemistry (all-trans) (Scheme 13.3.6). Such cyclisation occurs with a really amazing stereoselectivity and several new chiral centres with the correct stereochemistry are created in one single step ... 

The alkylation of cyclopentanoid enolate groups, which are part of polycyclic systems, is a common step in natural product syntheses, particularly in the synthesis of terpenoids and steroids. A high degree of stereoselectivity is usually encountered in such reactions, for example, in the preparation of the bicyclic compounds 17-2054 59. Steric, rather than electronic, control elements determine the diastereoselectivity. 

Arene activation by metal complexation is not always necessary for the cyclisation of samarium ketyls on to aromatic systems. Studies carried out by Reissig demonstrated the utility of these reactions for the synthesis of a wide variety of polycyclic systems, although yields and stereoselectivities depend highly on the substrate structure.68 One well-behaved system is represented by the cyclic y-naphthyl ketones 50-54, which cyclise with excellent diaster-eocontrol, thereby incorporating four- to eight-membered rings into the tetracyclic structures 55-59 (Scheme 5.38).68 Tetracyclic product 56 (n = 1) is of particular interest because of its steroid-like structure. 

The most important applications are involved in the synthesis of polycyclic systems. The cyclization reactions of suitably substituted 2-naphthyIcyclopentylacetic acids have been investigated in connection with syntheses of a,b aromatic ring steroids but the traditional Friedel-Crafts procedures proved disappointing. On the other hand, the cyclization shown in equation (41), which used hydrofluoric acid as... 

Garcia-Fandino, R., lose Aldegunde, M., Codesido, E.M. et al. (2005) RCM for the construction of novel steroid-like polycyclic systems. 1. Studies on the synthesis of a PreDs-Ds transition state analogue. J. Org. Chem., 70, 8281-90. 

In the investigation of the total synthesis of steroids, not only have new chemical reactions been discovered and ones known earlier modified, but extremely delicate methods for the selective performance of chemical transformations have been developed. Moreover, with the results obtained in total steroid synthesis, the stereochemistry of condensed polycyclic systems has been given a new impetus and further development. 

Stereochemistry of Polycyclic Systems. Two aspects of the stereochemistry of polycyclic compounds are of the greatest interest for the total synthesis of steroids, namely the comparative stability of the spatial isomers of these compounds and the influence on them of double carbon-carbon bonds in various positions of the cyclic system. 

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... 

Strategies based on two consecutive specific reactions or the so-called "tandem methodologies" very useful for the synthesis of polycyclic compounds. Classical examples of such a strategy are the "Robinson annulation" which involves the "tandem Michael/aldol condensation" [32] and the "tandem cyclobutene electrocyclic opening/Diels-Alder addition" [33] so useful in the synthesis of steroids. To cite a few new methodologies developed more recently we may refer to the stereoselective "tandem Mannich/Michael reaction" for the synthesis of piperidine alkaloids [34], the "tandem cycloaddition/radical cyclisation" [35] which allows a quick assembly of a variety of ring systems in a completely intramolecular manner or the "tandem anionic cyclisation approach" of polycarbocyclic compounds [36]. 

Sterols comprise a very important class of compounds in plant and animal systems. Bacteria and other organisms utilize cholesterol or related sterols in the synthesis and maintenance of their cell walls. True sterols are present in cyanobacteria to only a very small degree they are largely replaced with a steroid-like class of triterpenoid known as the hopanoids. The carbon frameworks of sterols and bacterial hopanoids are synthesized in essentially the same manner as other terpenes, however, the cyclization reactions to yield their polycyclic skeletons are unique. A variety of sterols and hopanoids are found in cyanobacteria and they are believed to have important cellular functions in cell wall structure and function. " As discussed in Section 2.06.5, many of the hopanoids also possess a polyalcohol chain derived from a sugar. ... 

The Robinson annulation has found extensive use in the synthesis of polycyclic ring systems, including steroids and other natural products containing six-membered rings. 

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