Convergent total synthesis of (±) myricanol, a cyclic natural diarylheptanoid

Abstract

Third total synthesis of the meta, meta-bridged diarylheptanoid: myricanol with remarkable anti-tau properties.

New synthesized polyoxygenated diarylheptanoids suppress lipopolysaccharide-induced neuroinflammation

“…In our investigation, we reported the prospect of new eleven linear polyoxygenated diarylheptanoids as a source of alternative anti-neuroinflammatory compounds. To this end, they were synthesized according to known methodology [14] and screened in LPS-triggered BV-2 microglial cells. The tested diarylheptanoids could be classified into three class: a) with double bond (4a, 4b, 4d and 4f); b) without double bond (5a, 5c, 5d, and 5e) and c) with one or two halides on the aryl rings and completely protected on hydroxyl groups (6b, 6c and 6d).…”

“…The requisite allylphenols 1a and 1b were accessed in two steps from commercially available 2,3dimethoxyphenol [13]. Coupling partners 2a, b and 3 were readily prepared from commercial methyl 3-(4-benzyloxyphenyl)propanoate [14,15]. With the key fragments 1a, 1b, 2a, 2b and 3 in hands, we attempted cross metathesis (CM) reactions as depicted in Scheme 1 [14,19,20].…”

“…Taking into consideration the biological importance of linear diarylheptanoids in general, and myricanol and curcumin in particular, we planned a straightforward access to a series of linear diarylheptanoid derivatives using the cross-metathesis reaction on readily available precursors 1a,b, 2a,b and 3 [13][14][15]. Terminal olefins 1-3 [14] were easily prepared and used to give access to new linear diarylheptanoids and to the cyclic one, myricanol. Herein some of these were differently protected, halogenated and reduced.…”

Unintended Formation of a 26-Membered Cycle in the Course of a Novel Approach to Myricanol, a Strained [7,0]-Metacyclophane

“…The latter underwent a regioselective iodination in ortho position of the benzyl ether using I 2 as well as Ag 2 SO 4 to give 7 in 83% yield. 9 Subsequent vinylation of the amide with a Grignard reagent allowed us to isolate the ,unsaturated ketone 8 in a quantitative yield upon quick hydrolysis with a strong acid to avoid the formation of a side product coming from the Michael addition of the released hydroxylamine onto 8. 16 Luche reduction furnished 9 in 88% yield with complete chemoselectivity.…”

Access to 12-Membered Cyclic ortho,meta-Diarylheptanoids: Total Synthesis of Actinidione via Isomyricanone

“…Since the discovery of curcumin in 1815 by Vogel and Pelletier, diarylheptanoids have been thoroughly investigated due to their unique architectural features as well as their broad range of biological activities . Indeed, many approaches have been explored for the synthesis of the appealing family of cyclic 13-membered meta , meta -bridged biphenyls . However, to the best of our knowledge, no route scouting has been described to prepare 12-membered ortho , meta -bridged biphenyls.…”