1. Parallel synthesis of 1,6-disubstituted-1,2,4-triazin-3-ones on solid-phase
Miao Hu, Wei Huang, Marc A Giulianotti, Richard A Houghten, Yongping Yu ACS Comb Sci. 2013 Jul 8;15(7):335-9. doi: 10.1021/co400064d. Epub 2013 Jun 13.
A parallel solid-phase synthesis of 1,6-disubstituted-1,2,4-triazin-3-ones from MBHA resin is described. The reduction of resin-bound nitrosamino acids provides hydrazines efficiently without affecting the amide bond. The trityl protected hydrazine is then reduced with borane, and cyclized with 1,1-carbonyldiimidazole. The desired products are cleaved from their solid support and obtained in good yield and purity. This methodology is of value for the rapid parallel preparation of these potentially bioactive molecules.
2. Cleavage and deprotection of peptides on MBHA-resin with hydrogen bromide
S S Wang, B S Wang, J L Hughes, E J Leopold, C R Wu, J P Tam Int J Pept Protein Res. 1992 Sep-Oct;40(3-4):344-9. doi: 10.1111/j.1399-3011.1992.tb00310.x.
Dilute hydrogen bromide in trifluoroacetic acid containing pentamethylbenzene and thioanisole was used in the cleavage and deprotection of peptides on MBHA-resin. Particular attention was paid to potential applicability of the method to kilogram scale synthesis of thymosin alpha 1. In the HPLC purification of the peptides, acetonitrile was replaced by relatively nontoxic isopropanol. The change should be economically and environmentally very attractive.
3. Synthesis and comparative properties of two amide-generating resin linkers for use in solid phase peptide synthesis
Fang-Kun Deng, Kalyaneswar Mandal, Sam Luisier, Stephen B H Kent J Pept Sci. 2010 Oct;16(10):545-50. doi: 10.1002/psc.1279.
Well-characterized resins of high purity are critical for effective solid phase peptide synthesis (SPPS). The quality of commercial (4-methyl)benzhydrylamine-resin (MBHA-resin), used for the synthesis of peptide amides, is not consistent and residual ketone functionalities are frequently present. Such ketone or aldehyde impurities lead to the formation of acylation-resistant deletion peptides in SPPS. To avoid these undesirable side reactions, we have optimized the preparation of two amide-generating linkers, which, in combination with aminomethyl-resin prepared directly from polystyrene resin, serve as alternatives to MBHA-resin for peptide amide synthesis. Then we have explored their comparative properties in SPPS. Use of sonication in reductive amination facilitated the synthesis of both benzhydrylamine (BHA) and MBHA linkers.
