Total Synthesis of (+)-Antroquinonol and (+)-Antroquinonol D

Abstract

The first total synthesis of (+)-antroquinonol and (+)-antroquinonol D, two structurally unique quinonols with a sesquiterpene side chain, is described. The route features an iridium-catalyzed olefin isomerization-Claisen rearrangement reaction (ICR), lactonization, and Grubbs olefin metathesis. The requisite α,β-unsaturation was achieved via the selenylation/oxidation protocol and elimination of β-methoxy group to provide two natural products from a common intermediate.

Studies Towards the Stereoselective Total Synthesis of 7‐O‐methylnigrosporolide

“…The selective desilylation [22] in compound 25 with NH 4 F in anhydrous methanol at 40°C to give, (2 S, 5R,11 S,Z)-11-[(tertbutyldimethylsilyl)oxy]-5-methoxy-2-(methoxymethoxy)dodec-3-en-6-yn-1-ol (26) in 80% yield. The alcohol 26 was oxidized with Dess-Martin Periodinane [23] in presence of NaHCO 3 in CH 2 Cl 2 at r.t., to afford, corresponding aldehyde 27, which was directly subjected Horner-Wadsworth-Emmons reaction [24] with triethylphosphono acetate and NaH in dry THF to give, trans-(E)-α,β-unsaturated ester (28) in 81% yield with excellent selectivity. On hydrolysis of compound 28 with LiOH followed by removal of the silyl ether with HF.Py [25] in dry THF at r.t., provided, (2E,4 S,5Z,7R,13 S)-13-hydroxy-7-methoxy-4-(methoxymethoxy) tetradeca-2,5-dien-8-ynoic acid (Seco-acid, 30) in 78% (over two steps) yield.…”

“…At this stage, the target is deprotection of MOM ether to get the final molecule. The deprotection of MOM ether was tried under various conditions [28] (Table 1), but could not achieve.…”

Applications of Mitsunobu Reaction in total synthesis of natural products

“…Compound 159 was transformed into dimethyl ether 160 after several steps. The latter was underwent a‐phenylselenylation‐selenoxide elimination to give the antroquinonol‐type dimethylated cyclohexenoid core 161a . Alternatively, simple exposure of 160 to LHMDS led to methanol elimination and simultaneous PNB deprotection to give 161b , readily .…”

Enhancement of antroquinonol production during batch fermentation using pH control coupled with an oxygen vector

“…The production efficiency is lower in solid‐state fermentation, and this limits the further biological evaluation of antroquinonol. Several organic chemists have reported on methods of total synthesis of antroquinonol . It is a good platform to obtain purified antroquinonol and its analogues.…”

“…Several organic chemists have reported on methods of total synthesis of antroquinonol. 31,32 It is a good platform to obtain purified antroquinonol and its analogues. While Antroquinonol has a densely substituted six-membered ring with its three contiguous stereocenters, and its synthesis requires long linear synthetic sequences (over 17 steps) and is not suitable for large-scale production yet.…”