title: Scaffold-directed traceless synthesis of tetrahydro-beta-carbolinehydantoins.
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.
authors.affiliation: Laboratory of Combinatorial Drug Discovery, Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan 300-10, ROC.
authors.forename: Chih-Hau
authors.initials: CH
authors.lastname: Chen
authors.forename: Chia-Mao
authors.initials: CM
authors.lastname: Chang
authors.forename: Hsia-Yuan
authors.initials: HY
authors.lastname: Chen
authors.forename: Jin-Ji
authors.initials: JJ
authors.lastname: Lai
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Sun
mesh_terms: D000470:Alkaloids / Q000737:chemistry; D002243:Carbolines / Q000737:chemistry*; D006827:Hydantoins / Q000138:chemical synthesis* / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D012995:Solubility
chemical_list: D000470:Alkaloids; D002243:Carbolines; D006827:Hydantoins; D006859:Hydrogen