On the synthesis of cardioactive steroid glycosides. On cardioactive steroids. XI

Abstract

A stereoselective β-glycosidation of digitoxose and digitoxigenin involving a 1–3 participation of a urethane group is described. The conversion of digitoxin (10) to its furyl derivative 11 and the rcoxidation of 11 to digitoxin and isodigitoxin (12), respectively, in high yield is reported for the first time. This is of fundamental importance for the use of the new glycosidation method in the total synthesis of digitoxin and its analogues.

Pre‐Activation‐Based Stereoselective Glycosylations

“…Besides C-2 protective groups, substituents on other positions of the glycan ring have often been suggested to participate in glycosylation and contribute to stereoselectivity under the traditional pre-mixed glycosylation condition. [70][71][72][73][74][75][76][77][78][79][80] However, direct evidence for participation has been scarce. Pre-activation approach provides an opportunity to investigate this type of participation since it is possible to trap and characterize the reactive intermediate prior to addition of acceptor.…”

“…Besides C‐2 protective groups, substituents on other positions of the glycan ring have often been suggested to participate in glycosylation and contribute to stereoselectivity under the traditional pre‐mixed glycosylation condition . However, direct evidence for participation has been scarce.…”

The glycosylation of steroids

“…The observed high b-stereoselectivity was presumably due to the intermediacy of the bridged species depicted in Scheme 85. 164,165 Scheme 82. LiClO 4 -mediated glycosylation under neutral conditions.…”

Syntheses of deoxy oligosaccharides

“…Wiesner et al [17] have developed a method which starts with 4-(p-methoxy)-benzoyl-3-methylurethane digitoxose 31. On treatment with the aglycon and p-toluene sulfonic acid, the 13-glycoside 32 is obtained in 83% with an 13 :~-ratio of 7: 1.…”

“…The mechanism is supposed to proceed via the charged species 227 and rather not an uncharged urethane. Further transformations are necessary to generate the 13-digitoxigenin glycoside 226 from the [3 derivative of 225 [17]. The naturally occurring ~,l~3-1inked oligosaccharides of, e.g., kijanimicin are synthesized either in a stepwise manner or following a one-pot procedure [109].…”