Scaffold-directed traceless synthesis of tetrahydro-beta-carbolinehydantoins.
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.
Chen
Chih-Hau
CH
Laboratory of Combinatorial Drug Discovery, Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan 300-10, ROC.
Chang
Chia-Mao
CM
Chen
Hsia-Yuan
HY
Lai
Jin-Ji
JJ
Sun
Chung-Ming
CM
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
D000470:Alkaloids; D002243:Carbolines; D006827:Hydantoins; D006859:Hydrogen