A Universal Approach to the Synthesis of Carbohydrate Conjugates of Polyhedral Boron Compounds as Potential Agents for Boron Neutron Capture Therapy
A. V. Orlova1, N. N. Kondakov1, A. I. Zinin1, B. G. Kimel’1, L. O. Kononov1 #, I. B. Sivaev2, and V. I. Bregadze2
#Phone: (495) 135-75-70; fax: (495) 135-53-28; e-mail: email@example.com 1Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninskii pr. 47, Moscow, 119991, Russia 2Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, Moscow, 117813, Russia Received: February 13, 2006; in final form: February 28, 2006
Abstract: A universal approach to the synthesis of carbohydrate conjugates with polyhedral boron compounds (PBCs) was developed. Oligosaccharide derivatives with amino group in aglycone moiety can be conjugated with PBC carboxy derivatives using N-methyl-N-(4,6-dimethoxy-1,3,5-triazin-2-yl)morpholinium chloride as a condensing agent. Both N-and O-glycosides differing in the conformation mobility around the glycoside bond were shown to be useful as oligosaccharides with a functional group in the aglycone moiety. This allows the application of this approach to the synthesis of PBC conjugates with a wide range of oligosaccharides isolated from natural sources can be transformed into N-glycosides with a functional group in aglycone. The approach was tested by conjugation of the carboxy derivatives of ortho-carborane and dodecaborate anion with lactose as a model oligosaccharide. Lactose, an easily available disaccharide, is a ligand of lectins expressed on the surface of melanoma cells. The approach suggested is the first example of the synthesis of such conjugates that does not require protective groups for the carbohydrate residue. It is especially important for obtaining dodecaborate-carbohydrate conjugates for which the removal of protective groups is often a non-trivial task.
Key words: boron neutron capture therapy, conjugates of polyhedral boron compounds with oligosaccharides, dodecaborate-carbohydrate conjugates, ortho-carborane-carbohydrate conjugates
Russian Journal of Bioorganic Chemistry 2006, 32 (6): 568-577