(±)‐Peharmaline A: A Pair of Rare β‐Carboline–Vasicinone Hybrid Alkaloid Enantiomers from Peganum harmala

Abstract

(±)‐Peharmaline A (1), a pair of rare β‐carboline–vasicinone hybrid alkaloid enantiomers with the hitherto unknown hybrid dimeric system, was isolated from the seeds of Peganum harmala L. Their structures, including absolute configurations, were determined by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. Plausible biogenetic pathways involving Mannich/Pictet–Spengler‐type and intermolecular Michael addition reactions are briefly discussed. Compound 1 exhibited significant cytotoxic activities against HL‐60, PC‐3, and SGC‐7901 cancer cell lines with median inhibitory concentration values of 9.2, 21.6, and 25.4 µm, respectively. However, two biosynthetically related precursors, harmaline and vasicinone, were inactive. This cytotoxic β‐carboline–vasicinone hybrid dimeric alkaloid may give some insight into the discovery of new lead compounds for cancer therapy.

Total Synthesis of an Anticancer Natural Product (±)‐Peharmaline A and Its Analogues

“…to give 11 (66 %), followed by reductive condensation to obtain the natural product (±)‐peharmaline A 1 in 47 % yield (Scheme ). All the spectroscopic data of the synthetic sample is in good agreement with the literature reports . Next, we wanted to convert the minor diastereomer 10′ obtained in the Pictet–Spengler reaction to the final product following the same procedure ( N ‐acylation followed by reductive condensation).…”

“…(±)‐Peharmaline A, a pair of novel β‐carboline–vasicinone hybrid alkaloid enantiomers with a unique hybrid dimeric system, was isolated by Wang et al in 2017 from the seeds of Peganum harmala L . Newly discovered (±)‐peharmaline A contains an unprecedented linkage of vasicinone and β‐carboline units.…”

Two‐in‐One Strategy for Palladium‐Catalyzed C−H Functionalization in Water

“…Deuterium-labeling experiments are discussed to provide insight into the mechanism. Examples include Komavine (1)( and Acetylkomavine), [4] Spiroindolone (2), [5] Tabertinggine (3), [6] Peharmaline A( 4), [7] Subincanadine B(5), [8] and the antimalarial drug NITD609 (6). As only aminute difference in reactivity exists between various CÀHb onds,r egioselective activation of these CÀHb onds constitutes ag reat challenge.T os olve such ap roblem, ad irecting group can help to direct the catalyst to activate proximal C À Hb onds via cyclometallated intermediates.However,the directing group needs to be preinstalled in the substrate and, upon finishing its mission, it is usually hard to remove from the product (Scheme 1a).…”

“…[3] Forg reener and more atom-economical transformations,a s well as taking into consideration the difficulty in separating the reversibly linked directing group from the product, the development of a" two-in-one" strategy for C À Hf unctionalization, in which the transient directing group is also used as ar eagent to react with the activated CÀHb ond, is highly attractive.Thetetrahydro-b-carboline skeleton bearing aquaternary carbon center at C1 is an important framework in natural products and pharmaceutical agents (Figure 1). Examples include Komavine (1)( and Acetylkomavine), [4] Spiroindolone (2), [5] Tabertinggine (3), [6] Peharmaline A( 4), [7] Subincanadine B(5), [8] and the antimalarial drug NITD609 (6). [9] Herein, based on the two-in-one strategy,w er eport ap alladium-catalyzed CÀHb ond activation at C2 of indole and pyridine in water followed by cyclization with at ransient directing group (imine group) to form the C À Cb ond.…”

“…Thetetrahydro-b-carboline skeleton bearing aquaternary carbon center at C1 is an important framework in natural products and pharmaceutical agents ( Figure 1). Examples include Komavine (1)( and Acetylkomavine), [4] Spiroindolone (2), [5] Tabertinggine (3), [6] Peharmaline A( 4), [7] Subincanadine B(5), [8] and the antimalarial drug NITD609 (6). [9] Herein, based on the two-in-one strategy,w er eport ap alladium-catalyzed CÀHb ond activation at C2 of indole and pyridine in water followed by cyclization with at ransient directing group (imine group) to form the C À Cb ond.…”