Using the 9-BBN Group as a Transient Protective Group for the Functionalization of Reactive Chains of α-Amino Acids

Abstract

Achieving chemoselectivity is a longstanding challenge in chemical synthesis. This problem has been addressed using different approaches, but a definitive solution is still pending. For instance, in peptide chemistry, particularly with amino acids containing side chains functionalities with reactivity patterns similar to the main functional groups, such as aspartic and glutamic acids­, and lysine and ornithine, specific semi-permanent protecting groups have been employed. The use of 9-borabicyclo[3.3.1]nonane (9-BBN-H) as a transient protective group for the selective protection of α-amino acids, which allows the chemoselective manipulation of the functional groups embedded in the side chains of the molecule, is described.

Key words

α-amino acids - selective protection - 9-BBN-H - protecting groups - oxazaborolidinones

• References

• 1 Bodanszky M. Principles of Peptide Synthesis . 2nd ed. Springer-Verlag; Berlin: 1993
• 2 Warren S, Wyatt P. Organic Synthesis: Strategy and Control . Wiley; London: 2007
• 3 Benoiton LN. Chemistry of Peptides Synthesis . 2nd ed. CRC Press; New York: 2005
• 4 Dent III WH, Erickson WR, Fields SC, Parker MH, Tromiczak EG. Org. Lett. 2002; 4: 1249
• 5 Sewald N, Jakubke H-D. Peptides: Chemistry and Biology . Wiley-VCH; Weinheim: 2002
• 6a Ojima I, Inaba S. Tetrahedron Lett. 1980; 21: 2077
• 6b Schwyzer R, Rittel W. Helv. Chim. Acta 1961; 44: 159
• 6c Neuberger A, Sanger F. Biochem. J. 1943; 37: 515
• 6d Sato M, Okawa K, Akabori S. Bull. Chem. Soc. Jpn. 1957; 30: 937
• 7 Bodanszky M, Bodanszky A. The Practice of Peptide Synthesis . 2nd ed. Springer-Verlag; Berlin: 1994
• 8 Lang K, Nuetzel K, Schubert F. German Patent 1130445, 1962 ; Chem. Abstr. 1963, 58, 1488a.
• 9 Sajiki H, Hirota K. Tetrahedron 1998; 54: 13981
• 10 Greene TW, Wuts PG. M. Protective Groups in Organic Synthesis . Wiley; New York: 1991
• 11a Bodanszki M, Tolle JC, Bdeshmane SS, Bodanszki A. Int. J. Pept. Protein Res. 1978; 12: 57
• 11b Dölling R, Beyermann M, Haenel J, Kernchen F, Krause E, Brudel M, Bienert M. J. Chem. Soc., Chem. Commun. 1994; 853
• 12a Nishimura O, Fujino M. Chem. Pharm. Bull. 1976; 24: 1568
• 12b Yajima H, Takeyama M, Kanaki J, Mitani K. J. Chem. Soc., Chem. Commun. 1978; 482
• 13 Microwaves in Organic Synthesis . Loupy A. VCH-Wiley; Weinheim: 2002
• 14 Kovavcs J, Kistaludy L, Ceprini MQ. J. Am. Chem. Soc. 1967; 89: 183
• 15 Neises B, Steglich W. Angew. Chem., Int. Ed. Engl. 1978; 17: 522
• 16 Nahm S, Weinreb SM. Tetrahedron Lett. 1981; 22: 3815
• 17 Ozinskas AJ, Rosenthal GA. J. Org. Chem. 1986; 51: 5047
• 18 Wolfe S, Wilson M.-C, Cheng M.-H, Shustov GV, Akuche CI. Can. J. Chem. 2003; 81: 883
• 19 Kwong FY, Klapars A, Buchwald SL. Org. Lett. 2002; 4: 581