Synthesis of (+)-Antroquinonol: An Antihyperglycemic Agent

Abstract

The total synthesis of antroquinonol has been accomplished through Suzuki-Miyaura cross-coupling and Barton-McCombie reaction, and the α,β-unsaturation was achieved through selenylation and oxidation protocols. In vitro and in vivo studies on the glucose-lowering properties of antroquinonol indicate that it is a potential antidiabetic agent.

Synthesis of (+)‐Antroquinonol and Analogues by Using Enantioselective Michael Reactions of Benzoquinone Monoketals

“…[ α ] D 23 = +52.2 ( c = 0.5, MeOH); ref. [7a] [ α ] D 24 = +48.6 ( c = 0.5, MeOH). 1 H NMR (500 MHz, CD 3 OD): δ = 5.91 (d, J = 6.1 Hz, 1 H), 5.21 (t, J = 7.0 Hz, 1 H), 5.13–5.04 (m, 2 H), 4.54–4.45 (m, 1 H), 3.59 (s, 3 H), 2.73–2.61 (m, 1 H), 2.32–2.21 (m, 1 H), 2.21–2.00 (m, 8 H), 2.00–1.91 (m, 2 H), 1.85–1.76 (m, 1 H), 1.66 (s, 3 H), 1.62 (s, 3 H), 1.60 (s, 3 H), 1.59 (s, 3 H), 1.16 (d, J = 7.0 Hz, 3 H) ppm.…”

“…Several related compounds are also found in A. cinnamomea including antroquinonol D ( 1d ), which has a similar structure to that of antroquinonol but without the methoxy substituent at the C‐3 position. Chemists have exercised great efforts to explore viable methods to synthesize antroquinonols with their reduced benzoquinone skeleton , . A key issue of the synthesis involves the formation of the densely substituted six‐membered ring with its three contiguous stereocenters.…”

“…Chen and co‐workers accomplished the first total synthesis of (+)‐antroquinonol, which featured an iridium‐catalyzed olefin isomerization–Claisen rearrangement reaction of a chiral bis(allyl) ether. [7a] They also developed a second synthesis of (+)‐antroquinonol by using d ‐mannose as a starting material from the chiral pool. [7b] These syntheses, however, require long linear synthetic sequences (over 17 steps).…”

“…[7a] They also developed a second synthesis of (+)‐antroquinonol by using d ‐mannose as a starting material from the chiral pool. [7b] These syntheses, however, require long linear synthetic sequences (over 17 steps). In contrast, our first‐generation synthesis of (±)‐antroquinonol and (±)‐antroquinonol D only requires six steps and uses Michael reactions of the appropriate benzoquinone monoketals with a dimethylcuprate reagent as the strategic key step .…”

Current Applications of Suzuki–Miyaura Coupling Reaction in The Total Synthesis of Natural Products: An update

“…This compound was reacted with readily accessible vinyl iodide 533 in the presence of Pd(dppf)Cl 2 as the catyst and Cs 2 CO 3 as base in DMF at ambient temperature under SMCR conditins to afford the key intermediate 534 in excellent yield. Antroquinonol 530 was obtained from compound 534 via a multi‐step reaction in satisfactory overall yield (Scheme ) …”