Synthesis of (−)-11-O-Debenzoyltashironin: Neurotrophic Sesquiterpenes Cause Hyperexcitation

Abstract

11-O-Debenzoyltashironin (1) is a member of the neurotrophic sesquiterpenes, trace plant metabolites that enhance neurite outgrowth in cultured neurons. We report its synthesis in six steps from a butenolide heterodimer via its likely biosynthetic precursor, 3,6-dideoxy-10-hydroxypseudoanisatin, here identified as the chain tautomer of 1. Access to the tashironin chemotype fills a gap in a comparison set of convulsive and neurotrophic sesquiterpenes, which we hypothesized to share a common target. Here we show that both classes mutually hyperexcite rat cortical neurons, consistent with antagonism of inhibitory channels and a mechanism of depolarization-induced neurite outgrowth.

Unusual Polycyclic Fused Product by Oxidative Enzymatic Dimerisation of 5-methylpyrogallol Catalysed by Horseradish Peroxidase/H2O2

“…No ambiguity was left on the final structure of 2′ using HRMS data and the molecular formula. To the best of our knowledge, this complex cage polycyclic structure is unprecedented in the literature and it shows some similarities with vinigrol [ 13 ] epicolactone [ 14 ] jiadifenolide [ 15 ] or (−)-11- O -debenzoyltashironin [ 16 ], which require multistep synthesis to be built. Several attempts to obtain monocrystals of 2 for X-ray spectroscopy were unsuccessful.…”

Contiguous Quaternary Carbons: A Selection of Total Syntheses

“…Although it is very appealing in terms of synthetic elegance, the Danishefsky synthesis was surpassed in efficiency when Shenvi and coworkers published their asymmetric 10-step synthesis 10 years later. Their approach was based on the central intermediate of Shenvi’s jiadifenolide synthesis [ 17 ], which was further modified towards ketone 58 to afford the natural product via Dieckmann cyclization ( Scheme 13 ) [ 18 ].…”

“…In mid-2019, less than two years after the reported isolation and structure elucidation [ 18 ], Rychnovsky and Burns published the first total synthesis of the pentacyclic sesquiterpene illisimonin A ( 72 ) [ 8 ].…”

Enantioselective Total Synthesis of Macfarlandin C, a Spongian Diterpenoid Harboring a Concave‐Substituted cis‐Dioxabicyclo[3.3.0]octanone Fragment

“…[13] Mukaiyama hydration of alkylidene lactone 12 took place with complete regioselectivity from the lactone face opposite the 1-methylcyclohexyl substituent to give alcohol intermediate 13. [14][15][16] The transformation of alcohol 13 to concavefunctionalized cis-2,8-dioxabicyclo[3.3.0]octan-3-one 17 was initially accomplished by way of three isolated intermediates. After initial silyl protection of the hydroxyl substituent, reaction with excess (iBu) 2 AlH provided a mixture of lactol epimers, which were directly oxidized to give cis-dioxabicyclooctanone 14 in high yield.…”