Total Synthesis of the Cardiotonic Steroid (+)-Cannogenol

Abstract

The total synthesis of (+)-cannogenol, an aglycon common to various biologically important cardiotonic glycosides, has been achieved. Synthesis of the versatile intermediate involves Mizoroki−Heck and intramolecular Diels−Alder reactions from the enantiomerically pure CDring segment, newly prepared in a multidecagram scale this time. Total synthesis by the site-selective transformations of the versatile intermediate demonstrated the applicability of our synthetic approach.

An Asymmetric Total Synthesis of Picrotoxinin through a Mizoroki–Heck Reaction

“…Finally, the total synthesis of 1 was completed by reduction of the bromoether moiety of 23 using Zn-Cu and NH4Cl in aqueous EtOH in 68% yield. The 1 Scheme 6. Total Synthesis of picrotoxinin (1).…”

“…In summary, we achieved the asymmetric total synthesis of picrotoxinin (1) with the Mizoroki-Heck reaction of enantioenriched tricyclic lactone 2 and isopropenyl bromide as the key transformation. The Mizoroki-Heck reaction enabled the highly diastereoselective introduction of the C4-isopropenyl group, although its regioselectivity was moderate.…”

“…Functional group manipulations including bromoetherification, epoxidation and dihydroxylation would provide picrotoxinin (1). First, we studied the synthesis of alkene 3 by the Mizoroki-Heck reaction using enantioenriched tricyclic lactone 2 (98% ee) 6 and isopropenyl bromide (Scheme 3).…”

Structural verification of petromyzestrosterol by total syntheses of both C14-epimers of its 3-O-methyl derivative

“…Our plan for the synthesis of 1b and 2b , the C14-epimers of the 3- O -methyl derivative of petromyzestrosterol, is shown in Scheme 1 and based on our previous synthesis of a highly oxygenated estrogenic derivative. 3 a Mizoroki–Heck reaction of bromoarene 3 and CD-ring segment 4 , 3 prepared in four steps from sorbic acid, would introduce the A-ring moiety with proper regio- and stereoselectivity. Subsequent reduction of the two carbonyl groups would provide hydroxy aldehyde 5 , from which the B-ring moiety could be constructed in a Friedel–Crafts-type cyclodehydration to provide estrogenic compound 6 .…”

Synthesis of Cardiotonic Steroids Oleandrigenin and Rhodexin B

“…Nevertheless, the availability of the β16-oxygenated cardenolides for medicinal chemistry exploration has been significantly limited by the lack of reliable synthetic routes to these steroids. While many recent studies have focused on developing concise approaches to cardiotonic steroids, , to date, there is only one reported synthesis of oleandrigenin ( 7 ) by Wicha and co-workers ( cf . Scheme ).…”