Nielsen, Daniel S3; Hoang, Huy N3; Lohman, Rink-Jan3; Diness, Frederik5; Fairlie, David P3
1 Department of Drug Design and Pharmacology, Faculty of Pharmaceutical Sciences, Københavns Universitet2 Medicinal Chemistry Research, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Administration, Department of Chemistry, Faculty of Science, Københavns Universitet5 Administration, Department of Chemistry, Faculty of Science, Københavns Universitet
The first total synthesis and three-dimensional solution structure are reported for sanguinamide A, a thiazole-containing cyclic peptide from the sea slug H. sanguineus. Solution phase fragment synthesis, solid phase fragment assembly, and solution macrocyclization were combined to give (1) in 10% yield. Spectral properties were identical for the natural product, requiring revision of its structure from (2) to (1). Intramolecular transannular hydrogen bonds help to bury polar atoms, which enables oral absorption from the gut.
Organic Letters, 2012, Vol 14, Issue 22, p. 5720-3