Structure, Total Synthesis, and Biosynthesis of Chloromyxamides: Myxobacterial Tetrapeptides Featuring an Uncommon 6-Chloromethyl-5-methoxypipecolic Acid Building Block

TY - JOUR

T1 - Structure, Total Synthesis, and Biosynthesis of Chloromyxamides

T2 - Myxobacterial Tetrapeptides Featuring an Uncommon 6-Chloromethyl-5-methoxypipecolic Acid Building Block

AU - Gorges, Jan

AU - Panter, Fabian

AU - Kjaerulff, Louise

AU - Hoffmann, Thomas

AU - Kazmaier, Uli

AU - Müller, Rolf

PY - 2018/10/22

Y1 - 2018/10/22

N2 - Soil-living microbes are an important resource for the discovery of new natural products featuring great structural diversity that are reflective of the underlying biosynthetic pathways as well as incorporating a wide range of intriguing small-molecule building blocks. We report here the full structural elucidation, total synthesis, and biosynthesis of chloromyxamides, a new class of tetrapeptides that display an unprecedented 6-chloromethyl-5-methoxypipecolic acid (CMPA) substructure. Chemical synthesis—including an approach to access the CMPA unit—was pursued to confirm the structure of the chloromyxamides and enabled determination of the absolute configuration in the CMPA ring. A model for the nonribosomal assembly of chloromyxamides was devised on the basis of the combined evaluation of the biosynthetic gene cluster sequence and the feeding of stable isotope-labeled precursors. This provided insight into the formation of the various chloromyxamide derivatives and the biogenesis of the CMPA unit.

AB - Soil-living microbes are an important resource for the discovery of new natural products featuring great structural diversity that are reflective of the underlying biosynthetic pathways as well as incorporating a wide range of intriguing small-molecule building blocks. We report here the full structural elucidation, total synthesis, and biosynthesis of chloromyxamides, a new class of tetrapeptides that display an unprecedented 6-chloromethyl-5-methoxypipecolic acid (CMPA) substructure. Chemical synthesis—including an approach to access the CMPA unit—was pursued to confirm the structure of the chloromyxamides and enabled determination of the absolute configuration in the CMPA ring. A model for the nonribosomal assembly of chloromyxamides was devised on the basis of the combined evaluation of the biosynthetic gene cluster sequence and the feeding of stable isotope-labeled precursors. This provided insight into the formation of the various chloromyxamide derivatives and the biogenesis of the CMPA unit.

KW - biosynthesis

KW - myxobacteria

KW - natural products

KW - secondary metabolites

KW - total synthesis

U2 - 10.1002/anie.201808028

DO - 10.1002/anie.201808028

M3 - Journal article

C2 - 30088846

AN - SCOPUS:85054160613

SN - 1433-7851

SP - 14270

EP - 14275

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

ER -