Total Synthesis of Two 8‐Oxoprotoberberine Alkaloids: Alangiumkaloids A and B

Abstract

A new and versatile synthetic route for 8‐oxoprotoberberine 17 through synthesis of isoquinolinone 16 and construction of a B‐ring is described. The key step is the synthesis of isoquinolinone 14 through thermal cyclization of 2‐alkynylbenzaldehyde oxime 12 to afford isoquinoline N‐oxide 13, followed by a Reissert–Henze‐type reaction. The first total synthesis of 8‐oxoprotoberberine alkaloid alangiumkaloids A and B was achieved by using this strategy.

Synthesis of Pyrido‐[2,1‐a]isoquinoline Derivatives via Gold(I)‐Catalyzed Intramolecular Cascade Reaction of Enamides

“…The stereoscopic configuration of compound 5 was determined by single‐crystal X‐ray diffraction [28] . Under the action of BBr 3 , product 2 a underwent a demethylation reaction to yield compound 6 with two hydroxyl groups, a valuable building block for further transformations [29] . Additionally, in the presence of NaH, product 2 a underwent two‐fold nucleophilic substitution reactions with iodomethane, forming compound 7 in high efficiency, which demonstrates its reactivity with other electrophiles.…”

“…[28] Under the action of BBr 3 , product 2 a underwent a demethylation reaction to yield compound 6 with two hydroxyl groups, a valuable building block for further transformations. [29] Additionally, in the presence of NaH, product 2 a underwent two-fold nucleophilic substitution reactions with iodomethane, forming compound 7 in high efficiency, which demonstrates its reactivity with other electrophiles. Treatment with Lawesson's reagent in THF converted compound 2 a into thioamide 8 in 97% yield.…”

Organocatalytic Asymmetric [4 + 2] Cyclization of Azadienes with Azlactones: Access to Chiral 3-Amino-δ-Lactams Derivatives

“…Lastly, Ubrelvy, an FDA-approved calcitonin gene-related peptide (CGRP) antagonist, showcases a chiral δ-lactam core skeleton . Moreover, a plethora of other biologically active compounds, such as Alangiumkaloid B, also feature δ-lactam motifs. As such, the pursuit of novel methods for constructing diverse, multisubstituted chiral δ-lactam frameworks has long been a focal point in the field of organic chemistry, attracting significant attention from researchers worldwide.…”

Synthesis of 3‐Aminopyrido[2,1‐a]isoquinolin‐4‐one Derivatives via Condensation of Azlactones with 1‐Alkyl‐3,4‐dihydroisoquinolines

“…The pyrido[2,1‐ a ]isoquinoline ring system is an important heterocyclic scaffold that can be found in many biologically active compounds. Among these are emetine, tetrabenazine, [1a–c] marine alkaloids Schulzeines A, B, C 1 a – c , [1a] as well as a large group of berberine alkaloids, [2a–e] structures of which include a dibenzo[ a , g ]quinolysine skeleton. The spectrum of biological activity of natural and synthetic pyrido[2,1‐ a ]isoquinoline derivatives is very wide.a, [a,3b] Among them, substances useful for the treatment and prevention of diabetes,a– [a–4d] neurodegenerative diseases, including Alzheimer's disease have been found, [3a,5a–b] as well as anti‐colitis, [6] anticancer [2b,7a–c] and anti‐inflammatory agents [5a,8a–d] .…”