Total synthesis and structural revision of engelhardione

Abstract

The total synthesis of the macrocyclic natural product engelhardione is reported. This effort led to the structural revision of the published structure of engelhardione to that of pterocarine. The revision reflects the change of the substitution pattern of one phenyl ether ring from the meta to the para position. To confirm, pterocarine (2) and its close regioisomer 3 were subsequently synthesized for comparison. Moreover, to the best of our knowledge, our synthesis of 1 represents the first example of a 14-membered macrocyclic diarylheptanoid with a meta-meta substitution pattern at the diphenyl ether moiety.

Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents

“…As illustrated in scheme 1, starting from 1,7-diarylhepten-3-one 2a - c , 18 the proposed structure ( 1a ) of engelhardione, pterocarine ( 1b ), and their regioisomer 1c were synthesized by a series of cross aldol condensations and selective hydrogenations, affording linear 1,7-diaryl-3-ketones as key intermediate 3a - c , followed by intramolecular Ullmann reactions to give the macrocyclic architectures 4a - c and final O -demethylation (Scheme 1). …”

“…1). 18 The structural revision was also subsequently confirmed by the Natarajan group 9 and the Chen group 19 . To further improve the efficiency of macrocyclization, we developed an efficient and modular microwave-assisted macrocyclization via intramolecular Ullmann coupling and investigated the scope and generality of a panel of substrates with different linkers, ring sizes, and substitution patterns.…”

Synthesis and evaluation of macrocyclic diarylether heptanoid natural products and their analogs

“…This structure was originally reported as the natural product engelhardione and was recently revised based on elegant work by the Sun group. 13 This is the first report describing the synthesis of racemic platycarynol.…”

Synthesis and antibacterial evaluation of macrocyclic diarylheptanoid derivatives

“…This improved protocol can be easily scaled up in gram scales compared to our previously reported method. 20 Next, in the presence of 10% sodium hydroxide solution, the aldol condensation of 2 and 3 yielded 4 as a yellow solid in 74% yield. Subsequent hydrogenation of 4 gave both 5 and 6 , which could be easily separated by flash column chromatography.…”