Synthesis of novel imbricatolic acid analogues via insertion of N-substituted piperazine at C-15/C-19 positions, displaying glucose uptake stimulation in L6 skeletal muscle cells

A new class of N-substituted piperazine analogues of imbricatolic acid have been designed and synthesized by using the appropriate synthetic routes in excellent yield. All synthesised compounds were screened for their in vitro glucose uptake stimulatory activity. Among them compounds 4b, 4e, 8b, and 8e triggered L6 skeletal muscle cells for glucose uptake at 54.73%, 40.79%, 40.90%, and 39.55% stimulation, respectively. Compound 4b has emerged as important lead compound showing potential antidiabetic activity. Illustration about their synthesis and in vitro glucose uptake activity is described.

Graphical abstractSynthetic analogues of naturally occurring diterpenoid, imbricatolic acid by insertion of amide and ester linkage at C-19 and C-15 positions have been prepared. All the analogues were evaluated for their ability to stimulate glucose uptake in L6 skeletal muscle cells.Figure optionsDownload full-size imageDownload as PowerPoint slide