Eine neue Totalsynthese von d,l‐Aldosteron Über Steroide, 158. Mitteilung

Abstract

A new total synthesis of d,l‐aldosterone‐21‐mono‐O‐acetate is described. It starts from the dodecahydro‐phenanthrene derivative I and the main synthetic pathway is indicated in the formula schemes by bold arrows. The ketalised oxo group in position 3 and the tetrahydro‐pyranyl ether of the 18,11β‐cyclohemiacetal could be preserved throughout the synthesis, and these protecting groups were simultaneously hydrolysed in the last step.

Quinones as Dienophiles in the Diels–Alder Reaction: History and Applications in Total Synthesis

“…As the Diels-Alder reaction is well suited to the preparation of substituted decalin systems, it is perhaps of little surprise that the reaction has been used extensively in the field of steroid synthesis. The quinone variant has also proved justifiably popular and has been employed by Woodward, [10] Sarett, [14] Dickinson, [15] Wettstein, [16] Walker, [17] and chemists from the Monsanto Chemical Company, [18] among others. Although, as a consequence of the stereospecificity of the reaction, the use of quinones as dienophiles will necessarily produce cisdecalins, the presence of the nearby carbonyl groups and the strong preference of such bicyclic systems to adopt a trans configuration enables epimerization to give the required ringjunction stereochemistry.…”

“…2.1. 3-Keto-D 4,9(11), 16 -etiocholatrienate (Woodward, 1951/52) Woodward was heavily involved in steroid chemistry during his early career, following his PhD studies on the use of the Diels-Alder reaction in "a synthetic attack on the oestrone problem". [19] He also famously collaborated with Konrad Bloch to unravel the details of steroid biosynthesis, [20] work for which the latter would be awarded the Nobel Prize in medicine in 1964, the year before Woodward received his in chemistry.…”

Chinone als Dienophile in der Diels‐Alder‐Reaktion – historische Entwicklung und Anwendungen in der Totalsynthese

“…Da die Diels‐Alder‐Reaktion gut geeignet ist zur Herstellung von substituierten Decalinsystemen, überrascht es kaum, dass die Reaktion auf dem Gebiet der Steroidsynthese umfassend genutzt wird. Die Variante mit Chinonen hat sich zu Recht als gängig erwiesen und wurde unter anderem von Woodward,10 Sarett,14 Dickinson,15 Wettstein,16 Walker17 und Chemikern der Monsanto Chemical Company18 genutzt. Obwohl die Verwendung von Chinonen als Dienophile, als Folge der Stereospezifität der Reaktion, zwangsläufig zu cis ‐Decalinen führt, wird durch das Vorhandensein benachbarter Carbonylgruppen und die starke Neigung derartiger bicyclischer Systeme, eine trans ‐Konfiguration einzunehmen, die Epimerisierung unter Bildung der Ringverknüpfung mit der benötigten Stereochemie ermöglicht.…”