The synthesis of cardenolide and bufadienolide aglycones, and related steroids bearing a heterocyclic subunit

Abstract

Covering: early studies through to March 2016Cardenolides and bufadienolides constitute an attractive class of biologically active steroid derivatives which have been used for the treatment of heart disease in traditional remedies as well as in modern medicinal therapy. Due to their application as therapeutic agents and their unique molecular structures, bearing unsaturated 5- or 6-membered lactones (or other heterocycles) attached to the steroid core, cardio-active steroids have received great attention, which has intensified during the last decade, in the synthetic organic community. Advances in the field of cross-coupling reactions have provided a powerful tool for the attachment of lactone subunits to the steroid core. This current review covers a methodological analysis of synthetic efforts to cardenolide and bufadienolide aglycones. Special emphasis is given to cross-coupling reactions applied for the attachment of lactone subunits at sterically very hindered positions of the steroid core. The carefully selected partial and total syntheses of representative cardio-active steroids will also be presented to exemplify recent achievements (improvements) in the field.

Discovery and characterization of a prevalent human gut bacterial enzyme sufficient for the inactivation of a family of plant toxins

“…These molecules were selected based on their chemical similarity to digoxin and their relevance in the context of the human gut. Cgr2 displayed robust activity only toward cardenolides, the family of plant toxins that includes the pharmaceutical agents digoxin and digitoxin as well as ouabain, which is used as an arrowhead poison ( Michalak et al, 2017 ). The cardenolide aglycones digoxigenin and ouabagenin were metabolized at a significantly faster rate than their glycosylated forms digoxin and ouabain, respectively (**p<0.01, Student’s t test).…”

Multicomponent Approach to the Synthesis of 4-(1H-indol-3-yl)-5-(4-methoxyphenyl)furan-2(5H)-one

“…Furan-2(5H)-one derivatives (γ-butenolides) are a very important class of heterocyclic compounds thanks to their natural occurrence and noteworthy biological activities [1][2][3]. As an example, the cardiotonic properties of steroids containing furanone moiety (cardenolides) are well documented [4,5]. Various compounds containing the γ-butenolide core possess cytotoxic [6], antibacterial [7], and anti-inflammatory activities [8,9].…”

Asymmetric Total Synthesis of Dankasterones A and B and Periconiastone A Through Radical Cyclization

“…It should also be mentioned that dankasterone B ( 1 b ) and periconiastone A ( 2 ) contain cis ‐fused A/B ring. cis ‐Decalin is present in diverse bioactive natural products [3] including alkaloids, terpenoids and steroids, [3b–c] such as ouabagenin ( 3 ), 6α‐hydroxycinobufagin ( 4 ) and batrachotoxin ( 5 ), as exemplified in Figure 1 b. These structural characters of 1 and 2 together with the angularly fused tricyclic ring system with two vicinal all‐carbon quaternary stereocenters pose a formidable challenge to synthetic chemists.…”