Concise Approach to (ent)-14 ß-Hydroxysteroids through Highly Diastereo-/Enantioselective Diels-Alder Reactions.

14ß-Hydroxysteroids, especially 14ß-hydroxyandrostane derivatives are closely related to the cardenolide skeletons. The latter were readily available through highly diastero/enantioselective Diels-Alder (DA) reactions requiring high pressure or Lewis acid activation. Moreover, in the presence of (R)- or (S)-carvone as a chiral dienophile, the DA-reaction takes place under chemodivergent parallel kinetic resolution control affording highly enantiomerically enriched 14ß-hydroxysteroid derivatives or the corresponding (ent)-14ß-hydroxysteroid derivatives.

Access to polyfunctionalized diquinanes, hydrindanes, and decalines via TiCl4 promoted Michael-aldol and Baylis-Hillman reactions.

The addition of 0.5 equiv of TiCl(4) to (cyclo)alkanones tethered to α,ß-unsaturated ketones afforded polyfunctionalized diquinanes, hydrindanes, and decalines. These products, resulting from a Michael-aldol or a Baylis-Hillman reaction, can be obtained with high or total diastereoselectivity in moderate to high yields. These scaffolds represent interesting building blocks for the synthesis of complex natural products.

Norrish-Prins reaction as a key step in the synthesis of 14ß-hydroxy-5α (or 5ß or Δ(5,6))-pregnane derivatives.

Numerous bioactive glycosteroids are characterized by aglycones bearing a 14ß-hydroxy pregnane skeleton like boucerin and isoramanone. In general, the syntheses of the latter are achieved by acidic hydrolysis of the corresponding glycosteroids. These aglycones were also obtained by a combined Norrish type I-Prins reaction starting from the corresponding 12-keto-pregnane derivatives. However, for the Norrish-Prins reaction, no reports describe the influence of the A/B ring junction (cis or trans or Δ(5,6) double bond) or the influence of the substitution pattern at position 20. Herein, we describe the use of Norrish type I-Prins reactions to synthesize isoramanone and boucerin derivatives and their A/B cis and trans analogs. The influence of the parameters mentioned above is also presented. These studies showed that the A/B ring junction has little influence on the Norrish type I-Prins reaction but that the substitution pattern at position 20 is important. The presence of a dioxolane group induced not only the formation of the desired 14ß-hydroxy pregnane derivatives in the highest yields but also the formation of new spiro derivatives.

Synthesis of Hoodigogenin A, aglycone of natural appetite suppressant glycosteroids extracted from Hoodia gordonii.

14ß-hydroxy pregnane glycosides extracted from Hoodia gordonii, a succulent plant isolated from Apocynaceae are suggested to have appetite suppressant properties in animals and humans. However, limited reports on biological studies concerning the appetite suppressant properties are available in the open literature. One reason for that is the poor availability of these glycosteroids because H. gordonii is a protected plant and the yield of extraction lies between 0.003% and 0.02%. Starting from 3α,12α-diacetoxy-pregnanone 1, we disclose in this report the synthesis of Hoodigogenin A, the aglycone of the natural 14ß-hydroxy pregnane glycosides extracted from H. Gordonii.