Recent developments in the isolation and synthesis of D-homosteroids and related compounds

Abstract

Both naturally occurring and synthetic D-homologs of compounds with a sterane skeleton exhibit diverse biological activity. The main sources of isolation are plants and marine organisms. The synthetic D-homosteroids are potential leads for drug discovery. This review focuses on steroids with a six-membered carbocyclic ring D and related compounds, the isolation or syntheses of which were reported between the mid-1990s and mid-2006.

Copper-catalyzed steroid reactions

“…In 2012 Wölfling and co-workers reported a simple and convenient synthetic route for the formation of novel 2α-triazolylcholestane derivatives. 16 For the preparation of novel steroid derivatives via copper(I)-catalysed azide-alkyne cycloaddition (CuAAC), 2α-azido-5α-cholestan-3-one 48 was chosen as starting compound. The synthetic strategy for the preparation of the starting azide is illustrated in Scheme 9.…”

“…Thus, both substrates 139 and 142 bearing the azide moiety in the side chain reacted with terminal alkynes rather easily, and the steroid fragment did not exert a noticeable steric effect on their reactivity. Since D-homo rearrangement is the expected metabolic degradation pathway of 17α-hydroxy-20-ketopregnanes 150 and D-homosteroids are known to exhibit valuable pharmacological properties 57 both 146 and the corresponding D-homoandrostane 145 were studied in CuAAC. As was expected, the reaction of these more sterically hindered azidosteroids proceeded more slowly and proved sensitive to the composition of a catalytic system.…”

Sensitized Aliphatic Fluorination Directed by Terpenoidal Enones: A “Visible Light” Approach

“…We synthesized two candidates that afforded selectively β-fluorinated products in yields up to 75% ( 9 and 10 ). Compound 10 represents a D-ring expanded enone (example of D-homo steroids that have been studied for various pharmacological activities) that provides C12 fluorination in 70% yield with >5:1 ratio of α:β isomers. In another case, we synthesized C2-functionalized progesterone to direct benzylic fluorination ( 9 ).…”