Synthesis of acetylene derivatives of lappaconitine

Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency

“…We studied the reaction of 5 -iodolappaconitine 17 [45] with phenyl acetylene 18 in the presence of carbon monoxide (CO) (as a one-carbon building block) under palladium catalysis. In order to avoid handling of gaseous CO, several methods employing a variety of CO sources have been developed (metal carbonyls, formic acid, carbon dioxide, etc.)…”

“…We investigated the carbonylative Sonogashira reaction of compound 17 and phenyl acetylene 18 and Mo(CO) 6 (2 equivalent) with a catalyst system consisting of [PdCl 2 (2 mol%)-Ph 3 P (4 mol%)] in the presence of Et 3 N (3 equivalent). Unfortunately, only 62% of the desired carbonylative product 19 at 85% conversion was obtained; as a major side-product the known non-carbonylative Sonogashira coupling product 22 [45] (yield 14%) was formed. In the case of employing Pd (OAc) 2 (2 mol%) as a palladium source, Ph 3 P (4 mol%) as the ligand and Et 3 N (3 equivalent) of this multicomponent reaction the desired compound 20 was not isolated.…”

“…Oxygen or water sensitive reactions were performed under the argon atmosphere. The starting material: 5 -ethynyllappaconitine 2 [39], 5 -iodolappaconitine 17 [45] and Ad 2 PBn • HBr [54,55] were synthesized, according to previously published procedures. Other reagents were purchased from commercial sources and were used without further purification.…”