Traceless synthesis of diketopiperazine fused tetrahydro-β-carbolines on soluble polymer support

• Published in: Molecular diversity 2011-05, Vol.15 (2), p.569-581
• Main Authors: Chanda, Kaushik, Chou, Cheng-Ting, Lai, Jin-Ji, Lin, Shu-Fen, Yellol, Gorakh S., Sun, Chung-Ming
• Format: Article
• Language: English
• Subjects: Amines - chemistry; Biochemistry; Biomedical and Life Sciences; Carbolines - chemical synthesis; Carbolines - chemistry; Combinatorial Chemistry Techniques; Diketopiperazines - chemistry; Full-Length Paper; Ketones - chemistry; Life Sciences; Models, Chemical; Organic Chemistry; Pharmacy; Polymer Sciences; Polymers - chemistry; Solubility
• ISSN: 1381-1991; 1573-501X
• DOI: 10.1007/s11030-010-9284-z

The Pictet–Spengler reaction, using polyethylene glycol immobilized tryptophan ester with a variety of ketones, was achieved by refluxing condition in acidic chloroform. The linear as well as cyclic ketones were employed. All the ketones were reacted within 6–8 h to furnish soluble polymer-supported tetrahydro- β -carboline in good yields. Further expansion at N -terminus of tetrahydro- β -carbolines was achieved through a reaction with chloroacetyl chloride. Finally, the 2,5-diketopiperazine skeleton was constructed over a β -carboline by amination of the resulting N -chloroacetamides and subsequent intramolecular cyclization leading to cleavage of the polymer; constitutes a traceless synthesis of tetracyclic molecular architecture. Significantly, this strategy affords a straightforward and efficient approach for the construction of biological promising molecules with high purity and good yields. Graphical Abstract