Catalytic Asymmetric Formal Total Synthesis of (−)-Triptophenolide and (+)-Triptolide

Abstract

Catalytic asymmetric formal synthesis of (−)-Triptophenolide and (+)-Triptolide have been achieved. Key reaction involves Palladium catalyzed asymmetric conjugate addition of aryl boronic acid to 3-methyl cyclohexe-1-none to form quaternary carbon. Claisen rearrangement and subsequent aldol reaction furnished trans-decaline key intermediate, which assured a formal total synthesis of (−)-Triptophenolide and (+)-Triptolide.Graphical Abstract Electronic supplementary materialThe online version of this article (doi:10.1007/s13659-016-0100-z) contains supplementary material, which is available to authorized users.

Construction of all-carbon quaternary stereocenters by catalytic asymmetric conjugate addition to cyclic enones in natural product synthesis

“…It was isolated by Kupchan and co-workers from the Chinese medicinal plant Tripterygium wilfordii Hook F in 1972. 145 In 2016, Qin and co-workers disclosed the formal syntheses of (+)-triptolide ( 15) and (−)-triptophenolide ( 16) 144 (Scheme 12). The enantioenriched conjugate adduct 160 was prepared by asymmetric conjugate addition of arylboronic acid 159 to enone 25 by using Stoltz's protocol; 135 160 was isolated Scheme 11 Selected examples of construction of all-carbon quaternary stereocenters by palladium-catalyzed asymmetric conjugate addition of arylboronic acid to enone in natural product syntheses reported before 2016.…”

“…147 The preparation of mastigophorene A Scheme 12 Formal syntheses of (+)-triptolide ( 15) and (−)-triptophenolide (16) (Qin, 2016). 144 Scheme 13 Atroposelective total synthesis of mastigophorene A (17) (Minnaard and Feringa, 2016). 147 (17) began with a palladium-catalyzed asymmetric conjugate addition of arylboronic acid 166 to 3-methylcyclopent-2-enone (156) under Minnaard's conditions 143 to afford adduct 167 in 55% yield with 92% ee.…”

Scalable Total Synthesis of (−)-Triptonide: Serendipitous Discovery of a Visible-Light-Promoted Olefin Coupling Initiated by Metal-Catalyzed Hydrogen Atom Transfer (MHAT)

“…Till now, nine groups have reported the semi-, total, or formal synthesis of triptolide. − These works could be grouped into three categories based on the strategies to secure the C10 quaternary carbon, by forging the C1–C10 bond, the C9–C10 bond or employing C10-embedded substrates (Figure a). Starting from tetralones, the C1–C10 bond could be constructed by alkylation , or asymmetric Robinson annulation .…”

An Overview of Saturated Cyclic Ethers: Biological Profiles and Synthetic Strategies

“…The fascinating structure and distinguished biological activity of TPL lead to considerable continued interest in their total synthesis and structure modification. In recent years, divergent total synthesis of TPL and its analogues have been reported [41,42,43,44]. However, these newly developed synthetic routes all adopted Yang et al’s strategy to assemble the three successive epoxide groups (Scheme 1).…”