Highly efficient biomimetic total synthesis and structural verification of bistratamides E and J from Lissoclinum bistratum.
The interesting biological activities of heterocycle-containing cyclic peptide-derived natural products, isolated from marine organisms over the past twenty years, have attracted the interest of many synthetic and natural products chemists. Bistratamides E-J, members of this class of natural products that were isolated very recently from Lissoclinum bistratum, exhibited cytotoxic activity against a human colon tumor (HCT-116) cell line. Here we report the first total syntheses of bistratamides E (1) and J (2) in overall yields of 19 and 34 %, respectively. The thiazole substructures have been synthesized by oxidation of their corresponding thiazoline substructures, which were obtained from cysteine containing peptides using a novel biomimetic approach wherein Val-Cys dipeptide units were converted to thiazolines by a bisphosphonium salt. The final macrocyclization was promoted efficiently using the combination of PyBOP and DMAP. This approach allows the use of readily available Fmoc-protected amino acids to make complex thiazole and oxazoline-containing natural products.
You
Shu-Li
SL
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Kelly
Jeffery W
JW
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D032701:Biomimetics; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D014561:Urochordata
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C491017:bistratamide E; C491018:bistratamide J