Cardiac glycosides. 7. Sugar stereochemistry and cardiac glycoside activity

Publisher Website
Google Scholar
Abstract
Digitoxigenin .alpha.-L-,.beta.-L-, .alpha.-D-, and .beta.-D-glucosides; .alpha.-L-,.beta.-L-,.alpha.-D-, and .beta.-D-mannosides; and .alpha.-L-rhamnosides were stereoselectively synthesized from the corresponding sugar tetrabenzyl trichloroacetimidates. The Na+,K+-ATPase receptor inhibitory activities of these glycosides (as a measure of receptor binding) were compared with those of digitoxigenin, digitoxigenin 6''-hydroxy-.beta.-D-digitoxoside, digitoxigenin .beta.-D-galactoside, and digitoxigenin .beta.-D-digitoxoside. The observed activities reveal that a given sugar substitutent may have a role in binding of some glycoside stereoisomers, but not others. With .alpha.-L- and possibly .beta.-L-rhamnosides, the 5''-CH3 and 4''-OH appear to have a predominant role in binding to the Na+,K+-ATPase receptor. Addition of a 6''-OH to form the corresponding mannosides dramatically disrupts the effect of both the 5''-CH3 and 4''-OH in prompting receptor binding of the .alpha.-L isomer. However, with the .beta.-L isomer, some influence of 4''-OH, 3''-OH, and 2''-OH binding remains. With .beta.-D-glycosides, binding via the "5''-CH3 site" appears to be of little importance and addition of a 6''-OH diminishes activity only slightly. With these .beta.-D-glycosides, an equatorial 4''-OH, axial 3''-OH, and equatorial 2''-OH groups appear to contribute to binding.

This publication has 0 references indexed in Scilit: