A Convenient and Efficient Synthesis of Dipeptidyl Benzoxaboroles and Their Peptidomimetics

Abstract

We have developed a convenient and efficient method for the synthesis of dipeptidyl benzoxaboroles and their peptidomimetics. The novel dipeptidyl benzoxaboroles were obtained by the protecting-group-free coupling of 6-amino-1,3-dihydro-2,1-benz­oxaborol-1-ol with various N-(arylcarbonyl)phenylalanines. Bioisosteric replacement of the terminal amide moiety of dipeptidyl benzoxaboroles by 1,3,4-oxadiazoles or 4H-3,1-benzothiazin-4-one provided their peptidomimetics with good molecular diversity. These transformations were based on the pluripotency of methyl (S)-2-isothiocyanato-3-phenylpropanoate and were highlighted by mild reaction conditions, high atom efficiency, and good to excellent isolated yields. This method is a valuable addition to the development of novel drug-like boronic acid molecules.

Key words

boronic acids - peptides - heterocycles - 1,3,4-oxadiazole - 4H-3,1-benzothiazin-4-one

• References

• 1 Boronic Acids: Preparation and Applications in Organic Synthesis and Medicine. Hall DG. Wiley-VCH; Weinheim: 2005
• 2 Adamczyk-Woźniak A, Cyrański MK, Żubrowska A, Sporzyński A. J. Organomet. Chem. 2009; 694: 3533
• 3 Torssell K. Ark. Kemi 1957; 10: 507 ; Chem. Abstr. 1958, 52, 82429
• 4a Lennarz WJ, Snyder HR. J. Am. Chem. Soc. 1960; 82: 2172
• 4b Haynes RR, Snyder HR. J. Org. Chem. 1964; 29: 3229
• 5a Yamamoto Y, Ishii J, Nishiyama H, Itoh K. J. Am. Chem. Soc. 2004; 126: 3712
• 5b Yamamoto Y, Ishii J, Nishiyama H, Itoh K. J. Am. Chem. Soc. 2005; 127: 9625
• 6 Oshima K, Aoyama Y. J. Am. Chem. Soc. 1999; 121: 2315
• 7 Alexander C, Smith CR, Whitcombe MJ, Vulfson EN. J. Am. Chem. Soc. 1999; 121: 6640
• 8 Dowlut M, Hall DG. J. Am. Chem. Soc. 2006; 128: 4226
• 9a Baker SJ, Zhang Y.-K, Akama T, Lau A, Zhou H, Hernandez V, Mao W, Alley MR. K, Sanders V, Plattner JJ. J. Med. Chem. 2006; 49: 4447
• 9b Rock FL, Mao WM, Yaremchuk A, Tukalo M, Crepin T, Zhou HC, Zhang YK, Hernandez V, Akama T, Baker SJ, Plattner JJ, Shapiro L, Martinis SA, Benkovic SJ, Cusack S, Alley MR. K. Science (Washington, D.C.) 2007; 316: 1759
• 10 Akama T, Baker SJ, Zhang Y.-K, Hernandez V, Zhou H, Sanders V, Freund Y, Kimura R, Maples KR, Plattner JJ. Bioorg. Med. Chem. Lett. 2009; 19: 2129
• 11 Seiradake E, Mao W, Hernandez V, Baker SJ, Plattner JJ, Alley MR. K, Cusack S. J. Mol. Biol. 2009; 390: 196
• 12 Ding D, Meng Q, Gao G, Zhao Y, Wang Q, Nare B, Jacobs R, Rock F, Alley MR. K, Plattner JJ, Chen G, Li D, Zhou H. J. Med. Chem. 2011; 54: 1276
• 13 Jacobs RT, Nare B, Wring SA, Orr MD, Chen D, Sligar JM, Jenks MX, Noe RA, Bowling TS, Mercer LT, Rewerts C, Gaukel E, Owens J, Parham R, Randolph R, Beaudet B, Bacchi CJ, Yarlett N, Plattner JJ, Freund Y, Ding C, Akama T, Zhang YK, Brun R, Kaiser M, Scandale I, Don R. PLoS Neglected Trop. Dis. 2011; 5: e1151
• 14 Qiao Z, Wang Q, Zhang F, Wang Z, Bowling T, Nare B, Jacobs RT, Zhang J, Ding D, Liu Y, Zhou H. J. Med. Chem. 2012; 55: 3553
• 15 Wrackmeyer B. Prog. Nucl. Magn. Reson. Spectrosc. 1979; 12: 227 ; Chem. Abstr. 1979, 91, 165665
• 16 Benoiton NL. Chemistry of Peptide Synthesis. Taylor & Francis; Boca Raton: 2006
• 17a Khalilullah H, Ahsan MJ, Hedaitullah M, Khan S, Ahmed B. Mini-Rev. Med. Chem. 2012; 12: 789
• 17b Bostrom J, Hogner A, Llinas A, Wellner E, Plowright AT. J. Med. Chem. 2012; 55: 1817
• 17c de Oliveira CS, Lira BF, Barbosa-Filho JM, Lorenzo JG. F, de Athayde-Filho PF. Molecules 2012; 17: 10192
• 18 Lamani RS, Nagendra G, Sureshbabu VV. Tetrahedron Lett. 2010; 51: 4705
• 19 Fieser LF, Fieser M. Reagents for Organic Synthesis. Wiley; New York: 1967: 295
• 20 Gütschow M, Schlenk M, Gäb J, Paskaleva M, Alnouri MW, Scolari S, Iqbal J, Müller CE. J. Med. Chem. 2012; 55: 3331