Total Synthesis and Structural Revision of (+)-Yaoshanenolide B

Abstract

(+)-Yaoshanenolide B was synthesized employing as a key step an endo- and face-selective Diels-Alder reaction between natural R-(-)-α-phellandrene and the exocyclic double bond of a 5-methylene-2(5H)-furanone. The dienophile furanone was prepared by photooxygenation of a suitably substituted 2-thiophenylfuran followed by dehydration of the resulting γ-hydroxybutenolide. Through this synthesis, the initially proposed structure for (+)-yaoshanenolide B has been revised to the 1R,2S,4R,7R,1″S diastereomer.

Four-Step Total Synthesis of (+)-Yaoshanenolides A and B

“…In our second approach, first, the total synthesis of (+)-yaoshanenolide B ( 2 ) was planned, which would allow us to compare and confirm the stereochemical outcome with respect to its proposed 3 and revised 6 structures. Thus, racemic dienophile 14a was prepared from γ-butyrolactone ( 15 ) in three steps (by a modification of Queneau’s procedure 13 ).…”

“…In addition, the absolute stereochemistry of the secondary hydroxyl functionality was assigned through the synthesis of corresponding MPA esters using ( S )-MPA and compared relative proton chemical shifts with that of reported data. 6 On the basis of the above analysis and known absolute stereochemistry of 12 , complete structures of both natural products yaoshanenolide A ((1 R ,2 S ,4 R ,7 R ,1″ S )- 1 ) and B ((1 R ,2 S ,4 R ,7 R ,1″ S )- 2 ) and their C1″-epimers ((1 R ,2 S ,4 R ,7 R ,1″ R )- 1a and (1 R ,2 S ,4 R ,7 R ,1″ R )- 2a ) were established (Figure 2 and Scheme 6).…”

“…The MPA-esters 24 and 24a were prepared using the reported procedure. 6 Compound 1 or 1a (0.02 g, 0.04 mmol) was dissolved in anhydrous CH 2 Cl 2 at rt, and then DMAP (3 mg), DCC (0.0.024 g, 0.12 mmol), and ( S )-MPA (0.019 g, 0.12 mmol) were added sequentially at rt. After completion of the reaction (2 h), the resulting mixture was absorbed on to the silica gel and purified by the column chromatography (SiO 2 , 2% EtOAc/hexanes), to afford 24 and 24a in 62 and 66% yield, respectively.…”

“…5 In 2016, Stratakis’s group reported a highly expedient first total synthesis and structural revision of (+)-yaoshanenolide B ( 2 ) via the Diels–Alder reaction between R -(−)-α-phellandrene and 5-methylene-2(5 H )-furanone derivative in 8 steps and 6.2% overall yield. 6…”

Furan Oxidation Reactions in the Total Synthesis of Natural Products

“…On the other hand, it allowed for synthesizing not only the target natural product but also its diastereomers. 10 The same group reported a biomimetic synthesis of merrekentrone C (25). Starting from furan-3-carbaldehyde (21) and lithium 4-methylpent-3-en-1-yn-1-ide (22), they synthesized furyl furfuryl ketone 23 and oxidized it with 1 O 2 to afford the target natural compound.…”