Metal‐Free Activation of C(sp³)–H Bond, and a Practical and Rapid Synthesis of Privileged 1‐Substituted 1,2,3,4‐Tetrahydroisoquinolines

Abstract

The reaction of cotarnine and acyl/aryl ketones in “green” solvents provides an efficient approach to an array of privileged 1,2,3,4‐tetrahydroisoquinolines in excellent yields by metal‐free activation of C(sp3)–H bonds. This one‐pot procedure takes place under base‐free conditions at room temperature, and tolerates a wide range of functionalities. The reaction is highly chemoselective, can be performed on a multi‐gram scale, and pure products are isolated by simple filtration without workup. Interestingly, the complementary two‐step procedure from cotarnine halide salts gives the Mannich products in good yields. The scope was elaborated to 9‐bromocotarnine salts to access a range of 9‐bromonoscapine‐derived analogues. The methodology has been developed considering the structural similarity of cotarnine derivatives to noscapinoids, which represent an emerging class of microtubule‐modulating anticancer agents.

Design, Synthesis, and Functional Studies on Noscapine and Cotarnine Amino Acid Derivatives as Antitumor Agents

“…A Barnstead/Electrothermal 9200 instrument was utilized to determine the melting points. 1 H and 13 C NMR spectra were recorded in DMSO-d 6 , CDCl 3 , and D 2 O on Bruker 300 and 400 MHz instruments, and coupling constants (J) are in Hertz (Hz), while chemical shifts (δ) are expressed in ppm. Highresolution mass spectra were recorded by using a Waters Micromass LCT Premier mass spectrometer.…”

“…It is one of noscapine’s oxidative degradation products. Cotarnine hydrochloride is employed as a hemostatic agent and is the key component in the synthesis of tritoqualine, which is an antiallergic drug . There exist several pharmaceutically active compounds with a cotarnine core that are capable of exhibiting considerable biological activities (Figure ).…”

“…Cotarnine hydrochloride is employed as a hemostatic agent and is the key component in the synthesis of tritoqualine, which is an antiallergic drug. 13 There exist several pharmaceutically active compounds with a cotarnine core that are capable of exhibiting considerable biological activities (Figure 1). So far, countless noscapine derivatives containing a cotarnine core with notable biological activities have been synthesized.…”

Novel Mechanistic Insights on the Photoredox Degradation of CECs Using Organic Photocatalysts

“…Separations were accomplished by UPLC on a Zorbax Eclipse Plus C18 column (4.6 x 100 mm, 3.5 m particle diameter). Cotarnine and opianic acid, were obtained from noscapine, according to the procedure reported in literature and used as standards in the HPLC-MS and HPLC-MS2 analysis [119].…”

“…Cotarnine and opianic acid were synthetised from noscapine, according to the methodology already published in literature. [119] 1g of NSC was dissolved in 8 ml of HNO3 14%. Solution was heated at 50°C for 2 hours.…”