WS9326 A is a tachykinin receptor antagonist and quorum sensing inhibitor discovered from several Streptomyces strains.The structure of WS9326 A features a(Z)-pentenylcinnamoyl moiety attached on a cyclic depsipeptide...WS9326 A is a tachykinin receptor antagonist and quorum sensing inhibitor discovered from several Streptomyces strains.The structure of WS9326 A features a(Z)-pentenylcinnamoyl moiety attached on a cyclic depsipeptide skeleton,which is biosynthesized by nonribosomal peptide synthetases(NRPS).The regioselective cyclization in the last step of NRPS catalysis,which is proposed to be catalyzed by a thioesterase(TE)domain in the last module,has not been experimentally characterized.We here report the synthesis of two substrate mimics(1 and 2)of the TE(WS9326 A-TE)in WS9326 A biosynthesis,by using Fmoc-based solid-phase peptide synthesis(SPPS)method.Compounds 1 and 2 are new compounds whose structures have been elucidated based on NMR and HRESIMS analyses.The N-terminal cinnamoyl moiety and C-terminal methylated L-Ser moiety in 2 were incorporated under the mild SPPS conditions.Given the isolation difficulties of substrate of WS9326 A-TE from the Streptomyces producers of WS9326 A,our synthesis of 1 and 2 set the stage for the reconstitution of WS9326 A-TE’s catalytic reaction in vitro in the future.展开更多
Resveratrol-based natural products have received considerable attention as synthetic targets due to their versatile bioactivities and unique structures.Herein,we disclose our efforts toward the syntheses of polynapsti...Resveratrol-based natural products have received considerable attention as synthetic targets due to their versatile bioactivities and unique structures.Herein,we disclose our efforts toward the syntheses of polynapstilbenes A and B,which possess[C8-O-C-C-C7]-type dihydrobenzofuran skeleton that is distinctive compared with the other reported resveratrol-derived natural products.Our approach,featuring an acid-catalyzed conjugate addition followed by cyclization of para-quinone methides and phenols,affords two advanced intermediates that represents the dimethyl-protected aglycon of polynapstilbenes A and B.展开更多
基金National Natural Science Foundation of China(Grant No.21877002,81673332,81573326 and 81741148)
文摘WS9326 A is a tachykinin receptor antagonist and quorum sensing inhibitor discovered from several Streptomyces strains.The structure of WS9326 A features a(Z)-pentenylcinnamoyl moiety attached on a cyclic depsipeptide skeleton,which is biosynthesized by nonribosomal peptide synthetases(NRPS).The regioselective cyclization in the last step of NRPS catalysis,which is proposed to be catalyzed by a thioesterase(TE)domain in the last module,has not been experimentally characterized.We here report the synthesis of two substrate mimics(1 and 2)of the TE(WS9326 A-TE)in WS9326 A biosynthesis,by using Fmoc-based solid-phase peptide synthesis(SPPS)method.Compounds 1 and 2 are new compounds whose structures have been elucidated based on NMR and HRESIMS analyses.The N-terminal cinnamoyl moiety and C-terminal methylated L-Ser moiety in 2 were incorporated under the mild SPPS conditions.Given the isolation difficulties of substrate of WS9326 A-TE from the Streptomyces producers of WS9326 A,our synthesis of 1 and 2 set the stage for the reconstitution of WS9326 A-TE’s catalytic reaction in vitro in the future.
基金Peking University Health Science Center(Grant No.BMU20130354)State Key Laboratory of Natural and Biomimetic Drugs,and the National Recruitment Program of Global Youth Experts(1000 Plan)
文摘Resveratrol-based natural products have received considerable attention as synthetic targets due to their versatile bioactivities and unique structures.Herein,we disclose our efforts toward the syntheses of polynapstilbenes A and B,which possess[C8-O-C-C-C7]-type dihydrobenzofuran skeleton that is distinctive compared with the other reported resveratrol-derived natural products.Our approach,featuring an acid-catalyzed conjugate addition followed by cyclization of para-quinone methides and phenols,affords two advanced intermediates that represents the dimethyl-protected aglycon of polynapstilbenes A and B.
