Chemoenzymatic collective synthesis of optically active hydroxyl(methyl)tetrahydronaphthalene-based bioactive terpenoids

Abstract

Starting from succinic anhydride and 2-methylanisole, a chemoenzymatic collective formal/total synthesis of several optically active tetrahydronaphthalene based bioactive natural products has been presented via advanced level common precursors; the natural product and antipode (-)/(+)-aristelegone B. Regioselective benzylic oxidations, stereoselective introduction of hydroxyl groups at the α-position of ketone moiety in syn-orientation, efficient enzymatic resolutions with high enantiomeric purity, stereoselective reductions, samarium iodide induced deoxygenations and tandem acylation-Wittig reactions without racemization and/or eliminative aromatization were the key features. An attempted diastereoselective synthesis of (±)-vallapin has also been described.

Asymmetric Total Syntheses of Di‐ and Sesquiterpenoids by Catalytic C−C Activation of Cyclopentanones

“…However, a different end‐game from Chavan's synthesis was pursued by merging the merits of other routes. Stereoselective α‐hydroxylation of 28 gave the compound 30 with a 7:1 dr . After further recrystallization, 96 % ee and >20:1 dr were obtained.…”

“…This natural product exhibits potent piscicidal activity and has been used by local fishermen to kill invasive fish. To date, a number of synthetic routes have been reported to access 7 , however, only two of them are asymmetric, and require 9–15 steps . We proposed that the α‐tetralone intermediate ( 28 ; Scheme ) in Chavan's synthesis could be accessed by the C−C/C−H cascade approach in a convenient manner, and would lead to a streamlined preparation of 7 .…”

Samarium(ii) iodide-mediated reactions applied to natural product total synthesis

“…In 2015, Argade and coworkers 28 developed the chemoenzymatic total synthesis of nine bioactive tetrahydronaphthalene-based natural products using antipode (−)/(+)-aristelegone B 28 as a single common precursor. Both (+)/(−)-isomers as potential building blocks were prepared through the late-stage efficient enzymatic resolution.…”

Expeditious diastereoselective synthesis of elaborated ketones via remote Csp3–H functionalization

“…1b)30313233. Classical approaches to introduce ketones in complex scaffolds heavily rely on direct oxidation/reduction of other functional groups, including alcohols, alkenes, alkynes, carbonyl derivatives and nitriles.…”