Synthesis of glucoconjugates of oleanolic acid as inhibitors of glycogen phosphorylase

Glucose derived inhibitors of glycogen phosphorylase

“…It was found that the homotrivalent derivatives 65 and 67 had slightly better inhibitory activity than the corresponding monovalent compounds 44b and 66, respectively. Homobivalent compounds 68 were made by CuAAC from N-v-azidoalkanoyl-b-D-glucopyranosylamines and 1,7-octadiyne, but had no effect on the enzyme [80].…”

“…Potentially heterobivalent compounds were designed by tethering pentacyclic triterpenes and D-glucose derivatives [80]: C-28 propargyl esters of oleanolic, ursolic, or maslinic acids were coupled by CuAAC with b-D-glucopyranosyl azide and N-v-azidoalkanoyl-b-D-glucopyranosylamines to give compounds 69 and 70, respectively. Derivatives with both per-O-acetylated and unprotected sugar parts were tested against GP and the best inhibitors are shown in Fig.…”

Tethered derivatives of d-glucose and pentacyclic triterpenes for homo/heterobivalent inhibition of glycogen phosphorylase

“…However, 56 binds to the catalytic site, 37 while 19 can be expected to occupy the allosteric site. 29 Thus, the comparable inhibitory activities may …”

“…Appending the sugar to the triazole via the C-6 position as in 55 (Chart 1) gave a very good inhibitor, although the O-peracetylated analogue had no activity at all. 29 The effect of the length of the linker between the sugar and the triterpene parts was studied in the o-triazolylalkanoylamide series (Scheme 4): with OA (22 vs. 23 and 24) and MA (28 vs. 29 and 30) derivatives the one-carbon linkage was significantly better than the longer ones, while among the UA compounds an opposite effect (27 vs. 25 and 26) was observed. Removal of the O-acetyl protecting groups in the o-triazolylalkanoyl-amide series (Scheme 4, 31-37) brought about no obvious difference.…”

“…The recently reported triterpene-glucose conjugates were not capable of this because the sugar parts were attached to the triterpene via the C-6 position. 29 Furthermore, some new bivalent glucose derivatives are also reported.…”