Polycyclic steroids

These two compounds have in common the presence of a polycyclic steroidal skeleton, and although in both syntheses the same strategy is used to build up ring A, the synthesis of cortisone shows a greater simplicity than the synthesis of conessine. 

Azabutadiene systems, as more or less formal carbonyl derivatives, have been used for [4 + 2] cycloaddition reactions. The fluoride-induced stereoselective transformation of (144) to the polycyclic steroid-like system (145), obviously proceeding via the corresponding reactive aza-o-quinodimethane (Scheme 67), shows the synthetic utility of such heterodienes. 

Finasteride is a synthetic polycyclic steroid prescribed for the systemic treatment of male pattern baldness. It is also promising in the treatment of... 

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). 

Intramolecular reaction can be used for polycyclization reaction[275]. In the so-called Pd-catalyzed cascade carbopalladation of the polyalkenyne 392, the first step is the oxidative addition to alkenyl iodide. Then the intramolecular alkyne insertion takes place twice, followed by the alkene insertion twice. The last step is the elimination of/3-hydrogen. In this way, the steroid skeleton 393 is constructed from the linear diynetriene 392(276]. 

As exemplified in the present procedure, the reaction has been optimized and extended in scope it affords functionalized benzocyclobutenes as well as substituted isoquinolines in high yields. Benzocyclobutenes have been used as intermediates in the synthesis of many naturally occurring alkaloids, - steroids,polycyclic terpenoids,and anthracycline antibiotics. The traditional routes leading to the preparation of benzocyclobutenes have been... 

The rotation of an axial CHjI group [cf. (3)] in a polycyclic saturated system is severely hindered by axial substituents on the same face therefore preferred orientations for both an 18- (Figure 12-1) and I9-CH2I (Figure 12-2) in steroids can be written ... 

Synthetic studies on biological activities of marine-origin polycyclic bis-steroid systems with 0-heterocyclic and pyrazine fragments or spirooxazoline fragment 99PAC1095. 

Polycyclic compounds are common in nature, and many valuable substances have fused-ring structures. For example, steroids, such as the male hormone testosterone, have 3 six-membered rings and 1 five-membered ring fused together. Although steroids look complicated compared with cyclohexane or decalin, the same principles that apply to the conformational analysis of simple cyclohexane lings apply equally well (and often better) to steroids. 

Epoxides are often encountered in nature, both as intermediates in key biosynthetic pathways and as secondary metabolites. The selective epoxidation of squa-lene, resulting in 2,3-squalene oxide, for example, is the prelude to the remarkable olefin oligomerization cascade that creates the steroid nucleus [7]. Tetrahydrodiols, the ultimate products of metabolism of polycyclic aromatic hydrocarbons, bind to the nucleic acids of mammalian cells and are implicated in carcinogenesis [8], In organic synthesis, epoxides are invaluable building blocks for introduction of diverse functionality into the hydrocarbon backbone in a 1,2-fashion. It is therefore not surprising that chemistry of epoxides has received much attention [9]. 

Dihydro-1-vinylnaphthalene (67) as well as 3,4-dihydro-2-vinylnaphtha-lene (68) are more reactive than the corresponding aromatic dienes. Therefore they may also undergo cycloaddition reactions with low reactive dienophiles, thus showing a wider range of applications in organic synthesis. The cycloadditions of dienes 67 and 68 and of the 6-methoxy-2,4-dihydro-1-vinylnaphthalene 69 have been used extensively in the synthesis of steroids, heterocyclic compounds and polycyclic aromatic compounds. Some of the reactions of dienes 67-69 are summarized in Schemes 2.24, 2.25 and 2.26. In order to synthesize indeno[c]phenanthrenones, the cycloaddition of diene 67 with 3-bromoindan-l-one, which is a precursor of inden-l-one, was studied. Bromoindanone was prepared by treating commercially available indanone with NBS [64]. 

Monteiro, P.R.R., Reis-Henriques, M.A., and Coimbra, J. (2000a). Plasma steroid levels in female flounder (Platichthys flesus) after chronic dietary exposure to single polycyclic aromatic hydrocarbons. Marine Environmental Research 49, 453 67. 

Polyene cyclizations are of substantial value in the synthesis of polycyclic terpene natural products. These syntheses resemble the processes by which the polycyclic compounds are assembled in nature. The most dramatic example of biosynthesis of a polycyclic skeleton from a polyene intermediate is the conversion of squalene oxide to the steroid lanosterol. In the biological reaction, an enzyme not only to induces the cationic cyclization but also holds the substrate in a conformation corresponding to stereochemistry of the polycyclic product.17 In this case, the cyclization is terminated by a series of rearrangements. 

Knowledge regarding biosyntheses has induced several biomimetic approaches towards steroids, the first examples being described by van Tamelen [10] and Corey [11]. A more efficient process was developed by Johnson [12] who, to synthesize progesterone 0-10 used an acid-catalyzed polycyclization of the tertiary allylic alcohol 0-7 in the presence of ethylene carbonate, which led to 0-9 via 0-8 (Scheme 0.3). The cyclopentene moiety in 0-9 is then transformed into the cyclohexanone moiety in progesterone (0-10). 

Some excellent examples of cationic polycyclizations, especially in the field of steroid synthesis, were described in Chapter 1. However, these polycyclizations can also be performed using a radical as initiator. Such reactions can be divided into those based on serial 6-mdo-trig cyclizations from polyene acyl precursors [92], radi-... 

The thermally and Lewis acid-promoted transannular Diels-Alder reactions have proven to be a powerful tool for the synthesis of steroids and other natural products [24]. A research team led by Takamura, Arimoto, and Uemura utilized this reaction to assemble the polycyclic skeleton of nakiterpiosin (1) [25]. Heating macrolide 39 at 160 °C gave 40 and 41 as a mixture of diastereomers in good yields. 

In the past, general chapters and reviews have been published, related to the characteristics of CL as analytical technique [7-9], mainly in the liquid phase [10-14], and its use as detection mode in flowing streams and immunoassay [15-17]. Two extensive reviews reported on the specific application of CL reactions according to the nature of the analyte (inorganic species, enzymes and nucleotides, acids and amines, carbohydrates, steroids, polycyclic aromatic compounds, and drugs) and covering the literature from 1983 to 1991 [18] and from 1991 to mid-1995 [19]. 

Proteins, Solid, Adsorption of Water on (Eley Leslie). Proteins and Nucleic Acids, Electronic Structure Proteins and Nucleic Acids, Influence of Physical Agents on Purine-Pyrimidine Pairs, Steroids, and Polycyclic Aromatic Carcinogens (Pullman). ... 

Steroids, Purine-Pyrimidine Pairs, and Polycyclic Aromatic Carcinogens (Pullman). ... 

In later studies by various groups, the enyneallene motif was incorporated into more complex hydrocarbon structures, allowing not only a better understanding of the Myers cyclization but also the generation of polycyclic hydrocarbons, some of them resembling the steroid core unit. Conceptually, these latter cyclizations are reminiscent of Johnson s biomimetic cyclization reactions with the main difference that here radical intermediates are involved rather than carbocations. Typical starting materials in these studies are the allenes 221 [87], 222 [88] and 223 [89], their cyclization behavior being discussed in Chapter 20. 

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