908287-35-4

Upstream product

• 153874-43-2 benzyl 1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carboxylate 
• 16502-01-5 tetrahydrobetacarboline 
• 102991-38-8 1,2,3,4-tetrahydro-β-carboline-1-carboxylic acid 
• 61-54-1 tryptamine 
• 1428771-86-1 C₂₁H₂₀N₂O₄ 
• 1428771-85-0 C₂₃H₂₄N₂O₅ 
• 64230-48-4 C₁₃H₁₃NO₃ 
• 53844-02-3 benzyl N-(2-bromoethyl)carbamate 

Downstream Products

• 205383-87-5 tert-butyl 2-oxospiro[indoline-3,3’-pyrrolidine]-1'-carboxylate 
• 1186530-95-9 benzyl 1,2-dihydro-1'H-spiro[indole-3,3'-pyrrolidine]-1'-carboxylate 

Relevant academic research and scientific papers

TCCA-mediated oxidative rearrangement of tetrahydro-β-carbolines: Facile access to spirooxindoles and the total synthesis of (±)-coerulescine and (±)-horsfiline

Multi-reactive centered reagents are beneficial in chemical synthesis due to their advantage of minimal material utilization and formation of less by-products. Trichloroisocyanuric acid (TCCA), a reagent with three reactive centers, was employed in the synthesis of spirooxindoles through the oxidative rearrangement of various N-protected tetrahydro-β-carbolines. In this protocol, low equivalents of TCCA were required to access spirooxindoles (up to 99% yield) with a wide substrate scope. Furthermore, the applicability and robustness of this protocol were proven for the gram-scale total synthesis of natural alkaloids such as (±)-coerulescine (1) and (±)-horsfiline (2) in excellent yields.

Spiro[pyrrolidine-3, 3′-oxindoles] and their indoline analogues as new 5-HT6 receptor chemotypes

Synthetic derivatives of spiro[pyrrolidinyl-3, 3′-oxindole] alkaloids (coerulescine analogues) were investigated as new ligands for aminergic G-protein coupled receptors (GPCRs). The chemical starting point 2′-phenylspiro[indoline-3, 3′-pyrrolidin]-2-one scaffold was identified by virtual fragment screening utilizing ligand- and structure based methods. As a part of the hit-to-lead optimization a structure-activity relationship analysis was performed to explore the differently substituted 2′-phenyl-derivatives, introducing the phenylsulphonyl pharmacophore and examining the corresponding reduced spiro[pyrrolidine-3, 3′-indoline] scaffold. The optimization process led to ligands with submicromolar affinities towards the 5-HT6 receptor that might serve as viable leads for further optimization.

Tandem aza-Michael/spiro-ring closure sequence: Access to a versatile scaffold and total synthesis of (±)-coerulescine

The total synthesis of the alkaloid (±)-coerulescine is presented. The key step of this approach is an efficient tandem aza-Michael initiated ring closure (aza-MIRC) process between ethoxymethylene-oxindole and benzyl(2-bromoethyl)carbamate. The potency of the aza-MIRC reaction was first tested onto less challenging Michael acceptors and led in good yields to the corresponding N-Cbz α-alkoxy-β-gem-disubstituted pyrrolidines. The resulting N-acyliminium precursor obtained from ethoxymethylidene-oxindole was efficiently converted in four steps, including 2 deprotections, into the targeted (±)-coerulescine.