Bio-inspired oxidative phenolic coupling: Total synthesis of the diarylether heptanoid (±)-pterocarine

Abstract

a b s t r a c tThe diaryletherheptanoid natural product, pterocarine, is expeditiously synthesized using a bioinspired intramolecular oxidative phenolic coupling of acerogenin G. The cyclization precursor is prepared from a simple cinnamic acid derivative in three high yielding synthetic operations. The key oxidative coupling is inspired by biosynthetic hypotheses; however, the oxidative coupling proceeds with concomitant hydroxylation of the diphenyl ether motif.

Recent Advances in the Synthesis of Diarylheptanoids

“…Saponification of 248 resulted in racemic (�)-226 (Scheme 64). [156] Florence Bedos-Belval and colleagues (2017) utilized copper catalyzed microwave assisted intramolecular Ullmann cyclization in the total synthesis of macrocyclic DAEH tedarene A 250. [157] The LDH 251 upon Ullmann cyclization reaction followed by elimination 250 to block ROS and nitrite production evoked by LPS, and inhibition of inflammatory cytokines IL-1β and IL-6 without toxic side effects.…”

Recent Studies on Cyclic 1,7-Diarylheptanoids: Their Isolation, Structures, Biological Activities, and Chemical Synthesis

“…Recently, Salih and Beaudry examined various oxidative cyclization conditions for acerogenin G ( 81 ) [165] and identified the classical phenoxy radical-forming agent PbO 2 in HOAc [166] as the oxidant of choice. Oxidative coupling of 81 with PbO 2 in HOAc, thus, resulted in cyclization with concomitant oxidative hydroxylation of the diphenyl ether and with esterification of a resident phenol, leading to acetyl pterocarine ( 82a ) and its regioisomer ( 82b ) in a ratio of approximately 3:1.…”