Total synthesis of WS9326A, a potent tachykinin antagonist from Streptomyces violaceoniger.
Total synthesis of the cyclic peptide lactone WS9326A, a potent tachykinin antagonist isolated from Streptomyces violaceoniger strain 9326, has been achieved via Cbz-Thr(Boc-allo-Thr-Asn-Ser(Bzl)-(E)delta MeTyr-Leu-D-Phe-OTce, which was cyclized (Phe and allo-Thr) using an active ester method with N-hydroxysuccinimide. Finally the unique N-acyl group, the 2-(1(Z)-pentenyl)cinnamoyl moiety, was introduced onto the amino group in the Thr unit. The key step of the synthesis involves the preparation of the E-isomer of the dehydro-N-methyltyrosine (delta MeTyr) unit. The debenzoxylation reaction of the threo- and erythro-isomer of the beta-benzoxy-N-methyltyrosine derivatives gave exclusively the Z-isomer of Cbz-Thr-delta MeTyr(MOM)-OMe, which was then converted to the desired E-isomer by photochemical isomerization of Cbz-Thr(TBDMS)-(Z)delta MeTyr(MOM)-Leu-D-Phe-OTce at a later step.
Shigematsu
N
N
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Kayakiri
N
N
Okada
S
S
Tanaka
H
H
D002851:Chromatography, High Pressure Liquid; D007536:Isomerism; D007783:Lactones / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000378:metabolism*; D013302:Streptomyces / Q000378:metabolism*; D015320:Tachykinins / Q000037:antagonists & inhibitors*; D047630:Depsipeptides
D007783:Lactones; D010456:Peptides, Cyclic; D015320:Tachykinins; C076469:WS 9326A; D047630:Depsipeptides