Steroids Cycloalkanes

Substituted cyclohexanes are the most common cycloalkanes and occur widely in nature. A large number of compounds, including steroids and many pharmaceutical agents, have cyclohexane rings. The flavoring agent menthol, for instance, has three substituents on a six-membered ring. 

Regioselective Substitution of Unactivated CH Bonds CH bonds in cycloalkanes (decaline, steroids) and alkanes bearing electron-deficient groups in remote posihons (1,2-dichlorocyclohexane, decanoic acid) can be regioselectively subshtuted at the anode by trifluoroacetate, acetate, or methoxide (Figs. 1, 2) [12-14]. 

These considerations apply to all cycloalkane derivatives, including steroids. However, the chair form of a ring is inherently more stable than the boat form. Moreover, the fnsed-ring natnre of the system lends it a very considerable rigidity, and cis-trans isomerization wonld necessitate the breaking and formation of covalent bonds. Therefore, steroid snbstitnents maintain their conformation at room temperature, whereas cyclohexane substituents usually do not. Steroids are classified according to their substituents in addition to their occurrence. 

Cycloalkanes (including X- and R-cycloalkanes and Bi-, Tri-... -cycloalkanes without Steroids)... 

This section includes oxidations of alkanes and cycloalkanes, alkenes and cycloalkenes, dienes, alkynes, aromatic fluorocarbons, alcohols, phenols, ethers, aldehydes, ketones and carbohydrates, carboxylic acids, nitrogen compounds, and organoelement compounds, such as boron, phosphorus, sulfur, selenium, and iodine compounds, and steroids. 

We will cover the conformations of cyclohexane in more detail than other cycloalkanes because cyclohexane ring systems are particularly common. Carbohydrates, steroids, plant products, pesticides, and many other important compounds contain cyclohexanelike rings whose conformations and stereochemistry are critically important to their reactivity. The abundance of cyclohexane rings in nature is probably due to both their stability and the selectivity offered by their predictable conformations. Nature probably forms more six-membered rings than all other ring sizes combined. 

The Favorski rearrangement is widely applicable. In the aliphatic series it leads to branched-chain carboxylic acids and in the cycloalkane series to ring contraction. The latter feature has been made use of in conversion of a six-membered into a five-membered steroid ring d and in the synthesis of cubane. 

P450 are found in complex molecules as well as in saturated hydrocarbons (alkanes and cycloalkanes). For example, the steroid progesterone is hydroxylated in positions 11(3, 17a and 21 to yield hydrocortisone. In practice, a nonactivated aUcyl group undergoes mainly to- and co - 1 oxidation. On the other hand, n-hexadecane is co-hydroxylated in the liver to yield hexadecanol which is further oxidized to hexadecanoic acid. For shorter chains, both terminal and (0 — 1 oxidations are observed (Fig. 31.5). Cyclic aliphatic systems are usually hydroxylated on the least hindered or most activated carbon atoms. 

In 1894, Alexie Favorskii published an early account of the rearrangement of simple acyclic a-halo ketones. This was followed in subsequent years with additional reports/ In 1914, he published the cyclic version featuring the ring contraction of 2-chlorocyclohexanone. This modification makes this transformation a reliable way to sjmthesize 1-substituted cycloalkane carboxylic acid derivatives. Later in the century, the rearrangement found application in the modification of steroids. Only in the last half of the 20 century has a clearer picture of the mechanism appeared. ... 

Steroids are a class of organic compounds that contain a characteristic arrangement of four cycloalkane rings joined to each other. All steroids are synthesized inside cells either from the sterols lanosterol (in animals and microorganisms) or from cycloartenol (in plants). Both lanosterol and cycloartenol are derived from the cycli-zation of the triterpene squalene (six isoprene units, 30C) [3-5]. In other words, squalene is the biochemical precursor to the whole family of steroids. Among all of the steroid biosynthesis, steroid hormone biosynthesis is the most concerned. 

This chapter deals with the names, physical properties, structural features, and conformational characteristics of the cycloalkanes. Because of their cyclic nature, members of this class of compounds can exhibit new types of strain, such as ring strain and transannular interactions. We end with the biochemical significance of selected carbocycles and their derivatives, including steroids. 

Besides the functionalization of alkanes and cycloalkanes, from an early stage on enzymatic steroid hydroxylation with wild-t) e whole cells was a broadly studied research field, leading to a range of industrial processes [131]. An early example is the production of hydrocortisone by microbial lla-hydroxylation starting from bile acid. Further examples are microbial hydroxylations running at a scale of up to 200m at the company Schering AG. 

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