Steroidal side chains

Hard carbon nucleophiles of organometallic compounds react with 7r-allyl-palladium complexes. A steroidal side-chain is introduced regio- and stereo-selectively by the reaction of the steroidal 7T-allylpalladium complex 319 with the alkenylzirconium compound 320[283]. 

The stereocontroUed syntheses of steroid side chains for ecdysone, cmstecdysone, brassinoHde, withanoHde, and vitamin D have been reviewed (185). Also, other manuscripts, including reviews on the partial synthesis of steroids (186), steroid dmgs (187—189), biologically active steroids (190), heterocychc steroids (191), vitamin D (192), novel oxidations of steroids (193), and template-directed functionali2ation of steroids (194), have been pubhshed. 

Deoxycholic acid (DCA) (17) and apoeholic acid (ACA) (18) are typical examples of the bile acid family of materials, but with the unique property of forming inclusion compounds with a wide variety of guest molecules 92). Partly due to the cis ring junction between rings A and B, and partly due to the conformation of the steroidal side chain these compounds present a convex hydrophobic P-face and a concave hydrophilic a-face, as shown for DCA (19), a classical aid to the formation of inclusion compounds 93). 

Bjorkemd, I., 1992, Mechanism of degradation ofthe steroid side chain in the formation of bile acids, 7. Lipid Res. 33 455-471. 

EiectrophUic alkylation in steroid side-chain biosynthesis... 

The 29-fluorophytosterols, members of a new class of selective pro-insecticides, have been synthesized and examined m vivo in tobacco hornworms. Dealkylation at C-24 of the steroid side chain by insects releases the latent poison fluoroacetate, resulting in dose-dependent reductions in growth rate, maximum weight, and survival when fed at 1 to 100 ppm to Manduca sexta. 

This sequence has great synthetic utility to replace carbonyl chains by a new carbonyl group and found application to degrade steroid side chains (equation 108). 

In most steroids the B-C and C-D rings are fused, usually in a trans manner. The lower side of the steroid is denoted a, the upper side of the steroid is denoted (3, usually drawn as projected helow the plane of the paper, which is shown as broken lines, and above the plane of the paper, which is drawn as solid lines. Thus, substituents attached to the steroid are also characterized as a and (3. Cholesterol has eight chiral centres, therefore 256 stereoisomers are theoretically possible, but only one exists in nature Stereogenic centres in steroid side chains are denoted preferentially with the R and S nomenclature. 

Stereocontrolled functionalization of steroidal side chains in nature is closely related to the function of steroids in living organisms. The regio- and stereochemistry of functional groups exert strong influence on the biological activities of steroids. Due to their multi-functional nature, the homoenolates provide an effective tool for synthetic efforts in this field. 

Steroid side chain.1 The key step in a method for stereocontrolled addition of the side chain to 17-kelo steroids is hydroboration of a 17(20)-(Z)-ethylidene steroid (I), which proceeds selectively to give 2, with the desired natural configuration at C,- and C2ft. The product reacts with most alkylating reagents in rather low yield, possibly because of stcric factors however alkylation with the anion of chloroacetonitrile (potassium 2,6-di-r-butyl-4-methylphenoxide) in T1IF gives the nitrile 3 in 60 70% yield. One added attraction of this route is that 9-BBN reacts preferentially with a 17(20)-double bond in the presence of a 5(6 )-double bond. 

For another approach to natural steroid side chains using the ene reaction, see Ethylaluminum dichloridc, this volume. 

Steroid side chain. Two laboratories- 4 have reported a stereocontrolled synthesis of the steroid chain with the natural conliguration at C. by the catalyzed... 

STEROID SIDE CHAIN 9-Borabicyelo-[ 3.3.11 nonane. Ethylaluminurn dichloride. 

Reductive desulfonylation.1 A stereocont rolled method for addition of the steroid side chain to a 17-keto steroid is outlined in scheme (I). The various steps proceed selectively to the sulfone 5. Reductive desulfonylation of 5 with Na/Hg, Na2HP04 in CH3OH gives the desired 6 (57% yield) and the undesired alkene in a 2 1 ratio. The desired stereoselectivity was obtained with lithium in ethylamine. The final step was hydrogenation of the 17(20)-double bond to give a protected cholesterol (7). 

A further example is the ready assignment of an olefinic resonance which appears in the spectrum of ruberoside G in addition to the H-ll signal at 5.3 ppm, common to asterosaponins. Its low-field chemical shift of 6.2 ppm (solid frame in Figure 5.1.4, and Figure 5.1.5) indicates the presence of a double bond in the steroidal side-chain in proximity to a deshielding functional group such as a carbonyl. 

Since asterosaponin mixtures consist of a variety of compounds with different combinations of reoccurring structural features (oligosaccharide or steroidal side-chains), this approach has already yielded valuable information for identif-ing known constituents and for selecting compounds of interest for further investigations, such as 2D stop-flow NMR spectra (see Section 5.1.2.5 below). 

Compound Retention time (min) m/z (D20) >n/J (D-H back-exchange) Saccharide chaine Steroidal side-chain... 

Stereocontrolled construction of the natural configuration 327 at C-20 in steroid side-chains is an important problem in steroid synthesis. In addition, preparation of the... 

Figure 5. Proposed structures of alkylthiophene moieties in kerogens and asphaltenes and their presumed flash pyrolysis products. Examples are give for alkylthiophene moieties with (a) linear, (b) isoprenoid, (c) branched and (d) steroidal side-chain carbon skeletons. Carbon skeletons are indicated with bold lines.

Immature kerogens and asphaltenes contain thiophene units in their macromolecular structure, which have mainly linear, isoprenoid, branched and steroidal side-chain skeletons. These units and possibly other sulfur-... 

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