Total Synthesis of the Post‐translationally Modified Polyazole Peptide Antibiotic Goadsporin

Abstract

The structurally unique polyazole antibiotic goadsporin contains six heteroaromatic oxazole and thiazole rings integrated into a linear array of amino acids that also contains two dehydroalanine residues. An efficient total synthesis of goadsporin is reported in which the key steps are the use of rhodium(II)‐catalyzed reactions of diazocarbonyl compounds to generate the four oxazole rings, which demonstrates the power of rhodium carbene chemistry in organic chemical synthesis.

Total Synthesis of the Cyclic Dodecapeptides Wewakazole and Wewakazole B

“…Although two total syntheses of wewakazole B have recently been reported, 4,5 its mode of action remains unknown. Given our previous work in the synthesis of post-translationally modified peptides, and particularly those containing azoles, [6][7][8][9][10] these two structures caught our attention as attractive targets for total synthesis. The two wewakazole structures differ only by the presence or absence of a methyl group on one oxazole and the identity of two of the peptide residues: the 5-unsubstituted oxazole, phenylalanine and valine present in wewakazole are replaced with a 5-methyloxazole, alanine and phenylalanine in wewakazole B.…”

“…Although two total syntheses of wewakazole B have recently been reported, , its mode of action remains unknown. Given our previous work in the synthesis of post-translationally modified peptides, and particularly those containing azoles, − these two structures caught our attention as attractive targets for total synthesis.…”

Total Synthesis and Biological Evaluation of Modified Ilamycin Derivatives

“…The N -prenylated tryptophan was replaced by an N -methylated analogue, since this structural change had no significant influence on the activity in the case of the cyclomarins and since N -methyl tryptophan is commercially available. We decided to use N -Alloc-protected amino acids as building blocks [ 40 , 41 ] in the linear peptide synthesis, because this protecting group can be removed via Pd-catalysis [ 42 ] and is therefore compatible with the other protecting groups used during the synthesis.…”

Dimerization of Phenylalanine: An Approach to Thiazoles and Oxazoles Involved S/O‐Insertion

“…They have the advantages of being non‐toxic, cheap, and easily available, which fulfill many of the requirements for components in modern organic synthesis. In recent years, the application of amino acids in organic conversions has been extensively investigated,–, especially for synthetic methodologies . In our continued efforts to activate and convert amino acids to heterocyclic compounds, we revealed the formal homo‐dimerization of phenylalanines to afford 2,5‐disubstituted pyridines biomimetically .…”

“…Thiazole is a heterocyclic compound that is widely present in natural products, synthetic drugs, and naturally occurring peptides –,,. In recent years, many different protocols have been reported for the synthesis of thiazole and derivatives .…”