|Budget Amount *help
¥7,800,000 (Direct Cost : ¥7,800,000)
Fiscal Year 1997 : ¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1996 : ¥6,000,000 (Direct Cost : ¥6,000,000)
In recent years, much attention has focused on the synthesis and development of glycosidase inhibitors because of an increasing awareness of the vital role playd by carbohydrates in biological processes. Therefore, the chemical and biochemical studies on glycosidase inhibitors may lead to understand the molecular basis of intractable diseases such as diabetes mellitus, cancer and AIDS,and may also provide us therapeutic approaches to them.
As part of an ongoing program to clarify the mode of action of glycosidase inhibitors, we have synthesized cyclophellitol, nagstatin and gualamycin, and their analogs having different configurations and functionalities.
Nagstatin is a natural inhibitor of N-acetyl-beta-D-glucosaminidase, and gualamycin is an antimite substance.
Herein, nagstatins including a variety of hydroxyl and triazole analogs have been synthesized from carbohydrates by inter-and intramolecular nucleophilic reaction of the imidazole and triazole moieties. Their glycosidase inhibiting activities were quite substrate-specific, indicating that the glycosidases recognize especially each carbons and configurations of the glycosidase inhibitors, and consequently, the inhibitors serve as antagonists of the corresponding glycopyranosides.
Total synthesis of gualamycin has been accomplished from three kinds of carbohydrates through glycosylation of a thio-phenol derivative of the disaccharide portion with a pyrrolidine-aglycone. The anti-mite activity of gualamycin was suggested to be due to its maltase inhibiting activity.