Novel Carboranyl Amino Acids and Peptides
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Successful BNCT will require the selective accumulation of 5–30 ppm 10B in tumor. 1 An attractive method for the delivery of boron to tumors is an antibody-based approach, which requires that ~103 boron atoms be delivered by each immunoprotein in order to achieve the necessary 10B concentrations. This requirement presents a chemical challenge which has led us to an interest in the precise chemical synthesis of hydrophilic boron-rich ‘trailer’ molecules. 2 We previously described the synthesis of anionic nido-carborane3 containing peptides 1 and 2 (derived from amino acid 3, Figure 1), their attachment to monoclonal IgG antibodies (Mabs) against the CEA antigen, and the in vivo characterization of these immunoconjugates. 4 However, because we found the sequential coupling reactions leading to the synthesis of 1 and 2 to be prohibitively slow under solid-phase conditions, we have recently begun to explore the synthesis of similar 10B-rich peptides in solution using a ‘doubling’ approach (segment synthesis), which is described herein.
KeywordsBoron Atom Amino Ester Propargyl Bromide Tetrabutylammonium Fluoride FMOC Protected Amino Acid
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- 3.Throughout this paper closo-carborane, o-carborane, or carboranyl refer to deriva rives of the closo-1,2-C2B10H12 cage, while nido-carborane refers to derivatives of the [nido-7,8-C2B9H11]- cage fragment.Google Scholar
- 5.All new compounds reported in this communication have been appropriately characterized (HRMS, HPLC, multinuclear NMR, etc.). Yields are reported for material homogeneous by NMR, TLC and/or HPLC.Google Scholar
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- 11.TBAF was expected to remove the FMOC protecting group (Happ, E., Scalfi-Happ, C., Chládek, S. (1987) J. Org. Chem. 52 (24), 5387–5391) and convert the closo carborane to its nido derivative (Tomita, H.; Luu, H.; Onak, T. (1991) Inorg. Chem., 30 (4), 812–815), concurrently with removal of the silyl group.Google Scholar