Sonogashira diversification of unprotected halotryptophans, halotryptophan containing tripeptides; and generation of a new to nature bromo-natural product and its diversification in water

• Published in: Chemical science (Cambridge) Vol. 8; no. 3; pp. 2039 - 2046
• Main Authors: Corr, M. J., Sharma, S. V., Pubill-Ulldemolins, C., Bown, R. T., Poirot, P., Smith, D. R. M., Cartmell, C., Abou Fayad, A., Goss, R. J. M.
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 01.03.2017
• Subjects: Biosynthesis; Blending; Bromination; Chemistry; Chemistry, Multidisciplinary; Cross coupling; Metabolites; Natural products; Physical Sciences; Precursors; Science & Technology; Synthesis (chemistry); CROSS-COUPLING REACTIONS; UNNATURAL PRODUCTS; IN-VITRO; COMPLEX; PEPTIDES; CONSTRUCTION; CHEMICAL-SYNTHESIS; PROTEINS; TRYPTOPHAN ANALOGS; DERIVATIVES
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c6sc04423a

The blending together of synthetic chemistry with natural product biosynthes is represents a potentially powerful approach to synthesis; to enable this, further synthetic tools and methodologies are needed. To this end, we have explored the first Sonogashira cross-coupling to halotryptop hans in water. Broad reaction scope is demonstrated and we have explored the limits of the scope of the reaction. We have demonstrated this methodol ogy to work excellently in the modification of model tripeptides. Furthermore, through precursor directed biosynthesis, we have generated for the first time a new to nature brominated natural product bromo-cystargamide, and demonstrated the applicability of our reaction conditions to modify this novel metabolite.