Position selectivity steroids

Be this as it may, the CH oxidation has become an attractive and promising preparative method in natural-product synthesis. For example, dioxiranes have been used to introduce selectively a hydroxy group at the C-25 position of steroids, a challenging task not readily achieved with other oxidants. A specific case is the TFD oxidation of brassinosteroid (equation 33) . 

Clearly, regio- and chemo-selectivities of this reagent are highly dependent on the substrate structure. Allylic oxidation to give enones has also been reported at the 11-position of steroids upon treatment with nitrosyl fluoride solutions. °°... 

We have largely been describing reactions on steroid substrates, which are conforma-tionally rigid and permit selective functionalizations by appropriate tethered templates. However, when the templates are linked to flexible chains, the results can be used to learn about the conformational preferences of such flexible chains. In one study [56], we examined the positional selectivities of insertion reactions into flexible chains by attached benzophenone units, a process we had also examined earlier [31], and compared the results with those from the intramolecular chlorination of such flexible chains by attached aryliodine dichlorides. The results were complementary. In another study [57] we used long-chain alkyl esters of nicotinic acid in radical relay chlorination, and saw some interesting selectivities reflecting conformational preferences in these nominally flexible cases. 

A number of steroids have been regioselectively acylated ia a similar manner (99,104). Chromobactenum viscosum hpase esterifies 5a-androstane-3P,17P-diol [571-20-0] (75) with 2,2,2-triduoroethyl butyrate ia acetone with high selectivity. The hpase acylates exclusively the hydroxy group ia the 3-position giving the 3P-(monobutyryl ester) of (75) ia 83% yield. In contrast, bacillus subtilis protease (subtihsia) displays a marked preference for the C-17 hydroxyl. Candida iylindracea]i 2Lse (CCL) suspended ia anhydrous benzene regioselectively acylates the 3a-hydroxyl group of several bile acid derivatives (104). 

Steroidal cis vicinal diols at the 1,2-, ° 2,3-, ° 5,6- or 11,12- " positions can be selectively protected as acetonides, prepared by reaction with acetone at room temperature or at higher temperatures in the presence of hydrochloric, perchloric or -toluenesulfonic acids. Cis nonvicinal-diols can be similarly protected. 

The high degree of stereoselectivity associated with most syntheses and reactions of oxiranes accounts for the enormous utility of these systems in steroid syntheses. Individual selectivity at various positions in the steroid nucleus necessitates the discussion of a collection of uniquely specific reactions used in the synthesis of steroidal epoxides. The most convenient and generally applicable methods involve the peracid, the alkaline hydrogen peroxide and the halohydrin reactions. Several additional but more limited techniques are also available. 

Aziridines can best be obtained by ring closure of amine derivatives which contain a tm 5-oriented leaving group at the -position, see (89). The variable conformational and steric influences in the steroid skeleton limit the generality of a particular synthetic method and necessitate a selection of reagents based on the position of fusion of the aziridine ring. 

Although there are many differences between these two groups of molecules, foe fundamental difference between them is that foe steroids do not possess foe long side chain attached to position 17 that occurs in sterols. Thus, if we are to use sterols as foe starting point for producing steroids, then we need to selectively remove this side chain. 

With nonracemic chiral diazoacetates the insertion process occurs with evident match/mismatch characteristics. This has been demonstrated in reactions of optically pure 2-methylcyclohexyl diazoacetates (Eq. 9) [85] and in carbon-hydrogen insertion reactions of steroidal diazoacetates (Eq. 10) [86], as well as with the synthesis of pyrrolizidines 36 and 37 [84]. The mechanistic preference for formation of a /J-lactone in Eq. 10 over insertion into the 4-position is not clear,but there are other examples of /J-lactone formation [87]. In these and related examples, selectivities in match/mismatch examples are high, and future investigations are anticipated to show even greater applicability. 

An impressive indication of the high regioselectivity of hydroxysteroid dehydrogenases (HSHDs) was reported for the oxidation of various hydroxyl groups at the steroid core ofbile acids [26] (Scheme 9.1). The hydroxy-substituents at positions 3, 7, and 12 could be selectively addressed depending on the hydroxysteroid... 

Microbiological oxidation has proven of enormous value in steroid chemistry, often affording selective means of functionalizing remote and chemically inactivated positions. It will bear mentioning that the 11-oxygen for all commercially available corticoids is in fact introduced by such a reaction carried out on plant scale. Preparation of the 1-dehydro analogue of 207 involves biooxidation to introduce the 16-hydroxyl. Incubation of 6a-fluoroprednisolone... 

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