Synthetic Approaches to Tricyclic Aminoketones in the Total Synthesis of Aspidosperma and Kopsia Alkaloids

Abstract

Aspidosperma and kopsia alkaloids are significant functional molecules because of their potent biological activities. Their intricate structures present an intrinsic synthetic challenge and thus attract significant attention from synthetic organic academic community. Over the past decades, a series of elegant strategies has been developed, in particular, the Stork's original Fischer indolization of tricyclic aminoketones 1. Herein, we report a comprehensive review on various synthetic approaches access to tricyclic aminoketones 1 and provide a practical guidance to readers whose are interested in employing tricyclic aminoketones 1 as versatile building blocks in the realm of total synthesis of aspidosperma, kopsia and structurally related alkaloids.

Recent Advances in the Total Synthesis of Aspidosperma and Kopsia Alkaloids Using Tetracyclic Pyridocarbazoles as Versatile Building Blocks

“…(2) Heathcock et al [6b] showcased an Michael addition of cyclopentanone to build quaternary carbon center. (3) The groups of She [6c,e] and Ma [6d,g] utilized Michael addition of carbazolones to install the quaternary carbon center (Scheme 12c).…”

“…[3a] Several reviews on the total synthesis of aspidosperma and kopsia alkaloids from different perspectives have been reported. [3] However, to the best of our from Beijing Medical University in 1998. In 2001, He started his independent career at CTGU where he is now a professor.…”

“…In particular, kopsia alkaloids except kopsihainanine A bear caged structures that lead to synthetic challenges. After more than half a century of research, organic chemists have developed a variety of elegant strategies for the total synthesis of aspidosperma and kopsia alkaloids, especially through common intermediates, such as Fischer indolization of tricyclic aminoketones (CDE‐ring), rearrangement of indoloquinolizidines (ABD‐ring), Diels‐Alder reaction of indole derivatives, cyclization of tetracyclic indolines (ABCE‐ring), and indole β ‐alkylation of tetracyclic pyridocarbazoles (ABCD‐ring) [3a] …”

Enantioselective Synthesis of α-All-Carbon Quaternary Center-Containing Carbazolones via Amino-palladation/Desymmetrizing Nitrile Addition Cascade

“…Carbazolones are prominent structural motifs found in a large family of biologically important and stereochemically rich indole alkaloids. − To date, total syntheses of more than 10 alkaloids of the Aspidosperma and Kopsia families have been achieved employing carbazolones as key intermediates (Scheme A). − A unique unifying feature of these studies is that multiple topologically differing stereocenters in each target were successfully installed utilizing the C20 all-carbon quaternary center as a stereochemical linchpin, thus highlighting the enabling potential of enantioenriched carbazolones in divergent syntheses toward a wide range of natural products.…”

Palladium-Catalyzed Asymmetric Tandem Denitrogenative Heck/Tsuji–Trost of Benzotriazoles with 1,3-Dienes

“…(Scheme b), the development of an asymmetric version of these reactions had not been explored until 2019 . Inspired by this asymmetric cycloaddition with allenes, we became very interested in the development of the asymmetric tandem denitrogenative Heck/Tsuji–Trost of benzotriazoles with readily available 1,3-dienes (Scheme c); if successful, a variety of enantioenriched hexahydrocarbazoles and indolines, which are ubiquitous structural motifs found in an array of biologically active monoterpene indole alkaloids, could be easily prepared (Figure ).…”