Total synthesis, structure, and oral absorption of a thiazole cyclic peptide, sanguinamide A

TY - JOUR

T1 - Total synthesis, structure, and oral absorption of a thiazole cyclic peptide, sanguinamide A

AU - Nielsen, Daniel S

AU - Hoang, Huy N

AU - Lohman, Rink-Jan

AU - Diness, Frederik

AU - Fairlie, David P

PY - 2012/11/16

Y1 - 2012/11/16

N2 - 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.

AB - 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.

KW - Animals

KW - Gastropoda

KW - Molecular Structure

KW - Peptides, Cyclic

KW - Stereoisomerism

KW - Thiazoles

U2 - 10.1021/ol3027347

DO - 10.1021/ol3027347

M3 - Journal article

C2 - 23130644

SN - 1523-7060

VL - 14

SP - 5720

EP - 5723

JO - Organic Letters

JF - Organic Letters

IS - 22

ER -