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Updated: Jul 14, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Scaffold-directed traceless synthesis of tetrahydro-beta-carbolinehydantoins
Chih-Hau Chen1, Chia-Mao Chang, Hsia-Yuan Chen
1Laboratory of Combinatorial Drug Discovery, Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan 300-10, ROC.
Abstract:
Pharmacologically interesting tetrahydro-beta-carbolinehydantoins have been prepared through four-step traceless synthesis by a combinatorial approach. Two-arm PEG 1 (MW approximately 4000) was used as a soluble polymer support and reacted with Fmoc-protected L-tryptophane 2 to form bis-ester 3. The resulting polymer-supported amino ester 3 was deprotected, and amino ester 4 underwent Pictet-Spengler reaction with varoius ketones to form tricyclic indoles 5. The nucleophilic piperidine in the tricyclic indole reacted with isocyanate to generate the urea intermediates and simultaneously intramolecular cyclization to release the target compounds 7 from the support in good yields.
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