Steroid framework

Nicolaou s approach 105) was somewhat different. The sulfone (336), upon heating, lost S02 and formed the benzocyclobutene (337) as an intermediate. Ring opening of (337) would lead to a steroid framework, which was then converted to ( + )-Estrone (332) 117). 

Chiral l,3-dioxin-4-ones photochemically react intermolecular with (cyclic) ethers, acetals, and secondary alcohols to give the addition products in reasonable yields. The radical addition was completely stereoselective at C-6 of the heterocycle <1999EJO1057>. The exocyclic diastereoselectivity, where relevant, was about 2 1 (Equation 30). In analogy, an intramolecular cascade reaction of a 1,3-dioxin -one derived from menthone was used to get a terpenoid or a steroid framework in optically active form <1997JA1129, 1999JA4894>. 

Jacobsen (Scheme 9). A steroid skeleton could also be hydroformylated by Rh/phosphite system in a moderate yield (Equation (3))/ The reaction occurs preferentially at the / -face of the steroid framework forming a new steroid with m-fusion of A and B rings. 

It is convenient to divide the subject into four sections. The first two, on chemical shift reagents and on relaxation studies, deal with techniques of line assignments and other facets of steroid behavior. The third, on substituent effects, lays the background for predicting steroid 13C chemical shifts and interactions of substituents with the steroid framework. In the fourth section the use of 13C NMR to solve problems in steroid stereochemistry is discussed. All chemical shift data are reported on the delta scale. 

As part of their review, Blunt and Stothers developed from their data a table of substituent chemical shifts for a variety of substituents at a wide range of positions. When applied to the appropriate steroid framework it becomes possible to make reasonably good predictions of steroid, 3C chemical shifts. The appropriate warnings about multiple substituent interactions are given. Considerable data on the interactions of multiple hydroxyl groups have been generated, (46, 47) and these provide useful guides for other substituents as well. 

Using a rigid steroidal framework to stabilize inermediates in this process, Lusinchi and co-workers have shown that the first stage of the reaction is a concerted Ea elimination of the anti-oriented a-hydrogen and oxaziridine oxygen to yield an iminal 52. 

The stereochemical requirements for backbone rearrangement of the steroid framework have been well established From deuterium-labelling experiments, the energetics and conformational dynamics of intermediate tertiary cations for model decyl systems compared with the rate of adjacent proton loss and the role and mobility of counter ion in the reaction are knownThe mechanism for formation of the rearranged isomers 87, 88, 89 and 90 with both configurations at C(20) was not investigated, but epimerization at C(20) in the total backbone rearrangement of the steroid nucleus has been previously reported . 

The most important features and references have been put together by Holland in his important monograph1731. At the present time, one could presumably almost consider that one or even several strains are known which are able to introduce a hydroxyl group at every carbon atom of the steroidal framework. Obviously, however, further work will have to be achieved in order to improve the selectivities and yields... 

The seventeen-carbon envelope would constitute the appropriate precursor of the steroid framework, considering a judiciously unsaturated macrocycle to manage a triple transannular cascade (strategy D). 

Squalene is very important in nature as it is the precursor of steroids, a family of molecules that serve as hormones in numerous organisms. The formation of the steroid framework from the mono-epoxide of squalene is shown in Figure 2.15. 

Nemeto, H., Yoshida, M., Fukumoto, K. and lhara, M. (1999) A novel strategy for the enantioselective synthesis of the steroidal framework using cascade ring expansion reactions of small ring systems - asymmetric total synthesis of (-l-)-equilenin. Tetrahedron Lett., 40, 907-10. 

Zard has studied the isomerization/Mislow-Evans rearrangement of vinyl sulfoxides such as 237, arising from enolate addition to alkynyl sulfoxides [Scheme 18.60). Isomerization of 237 to the allylic sulfoxide 238 enabled the [2,3]-sigmatropic rearrangement to a-hydroxy-a-vinyl ketone 239. In this case, diastereoselectivity was low in formation of the carbinol center within a steroid framework. Additions to allenyl sulfoxides provide a similar sequence, leading to 2-propenyl substitution at the tertiary alcohol center (not shown). 

Steroidal frameworks have been much used in synthetic ion transport designs. Cholate oligomers synthesized from polyamines and cholic acid derivatives represent another class of ion transporters (Figure 12). These compounds, inspired by squalamine antibiotic, are also known as molecular umbrellas because of their amphomorphism. Depending on the polarity of the medium, the hydrophilic cholate faces are exposed or hidden to the surface of the umbrella. These compounds such as 22 are active sodium... 

Cardiotonic steroid framework (cis A/B, trans B/C, as CID ring system)... 

Yeung and coworkers oxidize the allylic position of alkenes using a combination of phenyliodine(III) diacetate and t-butyl hydroperoxide in an ester solvent. A variety of substituted cyclic alkenes, including steroid frameworks, can be oxidized to a,P-unsaturated ketones. Ester solvents proved crucial for the success of the reaction, leading to the supposition that coordination of the carbonyl of the ester to the iodine center is necessary for the reaction to proceed. 

The surmoimting role of configuration and conformation on the regioselectivity of this elimination emerged convincingly from the clearresults observed with the epimeric steroidal sulfoxides 504 and 505. Only in the transition states 504 and 505 is the bulky adamantyl residue kept away from any interaction with the steroid framework and this leads to hydrogen abstraction from Cj in the first case and from C4 in the latter [178]. 

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