Steroid backbone

The available information on the pharmacology of STS inhibitors is restricted to a few in vitro and in vivo models. From all steroidal compounds, the irreversible inhibitor EMATE was found to be the most potent STS inhibitor with an IC50 of 65 pM [ 107]. However, it has been proposed that the sulfamate moiety of EMATE irreversibly binds to the active site and releases the steroidal backbone estrone. This means that EMATE, although a potent inhibitor of STS, counteracts its own effect by releasing estrone. The most potent derivative from a series of sulfamoyloxy-substituted stilbenes inhibited the growth of MCF-7 breast cancer cells with an IC50 value of 13 nM [111]. 

When the enolate is nearer the steroid backbone diastereoselectivity is higher. Methylation of the methyl ester of 3/i-tetrahydropyran-2-yloxypregn-5-en-21-oic acid 4 by means of LDA in tetrahydrofuran and iodomethane furnished the pure, crystalline (207 )-isomer 5 in 91 % yield. 

Cyclodextrin-substituted molecular channel approaches have now been extended to include acyl substituents through a covalent bond formation. Stearoyl and methyl cholate-substituted cyclodextrins 10 and 11, respectively, have been synthesized. It may be worthwhile commenting on the molecular design of methyl cholate-substituted a-cyclodextrin. All of the ether groupings are convergent at the inner side of the steroidal backbone of a bent structure to make the molecule amphiphilic. Once the cyclodextrin derivative is incorporated into the membrane phase, it may easily be expected that the ether parts are assembled inside the channel in the sea of hydrophobic lipid molecules and the hydrophobic steroidal skeletons cover its outside to stabilize the inner hydrophilic pore (Figure 13). 

Figure 13. a-Cyclodextrin-based bimotecular ion channels, (a) Hexatcar-boxymethyh-substituted a-cydodextrin combined with dioctadecyldimethylam-monium cation to afford hexa ion pairs 9, hexa(stearoyl)substituted a-cyclodextrin tO, and hexa trimethylcholyl)-substituted a-cydodextrin 11. (b) A hypothetical side view for the passage of metal ion through a hydrophilic channel wall comprised of ether network convergently extended from steroidal backbone. 

Figure 18.1 Ring and atom numbering for the steroid backbone. For chiral centers, notethat a implies a substituent is down (dotted line) and 3 implies up (solid line).

Enyne systems are also capable of impressive multiple RRM transformations. For the first such example see Ref. [119]. The reaction of a ruthenium alkyli-dene with an alkyne produces a new vinyl alkylidene, which can participate in further intramolecular or intermolecular metathesis reactions to form fused ring systems. This has led Grubbs to designate alkynes in such systems as relays . In a noteworthy example, Zuercher et al. [ 120] constructed the four fused rings of the steroid backbone 68 in one efficient step using tandem enyne re-... 

By analogy with what has gone before, you might now expect a tame hydration or reduction of this cation. Nothing of the sort A rearrangement occurs in which five consecutive 1,2-shifts are followed by an elimination. Since this reaction organizes the backbone of the steroids, it is often called the steroid backbone rearrangement. 

Complex rearrangements involving both the steroid backbone and the cholestane side chain were observed when either the Westphalen diacetate (252) or 5a-cholestane-2a,5-diol (253) was treated with HF at —60 °C. The 25-fluoro-product (254) was isolated in low yield from the 2,5-diol, and an analogous product resulted from the Westphalen diacetate. Inversion of the configuration at C-20 to give the unnatural (20S)-isomer is thought to involve stereospecific hydride transfer from C-25 to a C-20 carbocation subsequent nucleophilic attack at C-25 gives the 25-fluoro-compound. A hydride transfer from C-20 to C-13 is postulated to account for... 

Buxozine-C (22) was isolated from Buxus sempervirens It is the first buxus alkaloid having a tetrahydrooxazine heterocycle fused in positions 16 , lip of the steroid backbone. 

All genins examined in this study can be divided into classes with (1) a fully saturated steroid backbone (I - VIII), (2) a 14-ene-steroid backbone ( IX XI) or (3) an 8(14)-ene-steroid backbone (XII). Crystallographic analysis of these genins revealed that the A and B rings and most of the C rings are nearly identical. It therefore seems reasonable to assume that this constant portion of the molecule must fit into the... 

Ene D-Ring Structure. The change in the steroid backbone and associated D-ring conformation greatly reduces the steric interactions between the lactone ring hydrogens and the... 

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