Eri Fukushi

Sesquiterpene dimers from Chloranthus japonicus

Five novel dimeric sesquiterpenes, shizukaols E-I, consisting of two lindenane units were isolated from the roots of Chloranthus japonicus. Their structures were elucidated principally by 1D- and 2D-NMR methods. Three of them have a unique pendent macrocyclic ester ring found previously in shizukaol B.

Luteophanols B and C, new polyhydroxyl compounds from marine dinoflagellate Amphidinium sp.

Abstract Luteophanols B (1) and C (2), new polyhydroxyl linear carbon-chain compounds, have been isolated from the cultured marine dinoflagellate Amphidinium sp. The structures of 1 and 2 were elucidated by detailed analyses of two-dimensional NMR data containing HMBC, HMQC-RELAY, CH2-selected E-HSQC, and CH2-selected E-HSQC-TOCSY.

Escherichia coli allows efficient modular incorporation of newly isolated quinomycin biosynthetic enzyme into echinomycin biosynthetic pathway for rational design and synthesis of potent antibiotic unnatural natural product

Natural products display impressive activities against a wide range of targets, including viruses, microbes, and tumors. However, their clinical use is hampered frequently by their scarcity and undesirable toxicity. Not only can engineering Escherichia coli for plasmid-based pharmacophore biosynthesis offer alternative means of simple and easily scalable production of valuable yet hard-to-obtain compounds, but also carries a potential for providing a straightforward and efficient means of preparing natural product analogs. The quinomycin family of nonribosomal peptides, including echinomycin, triostin A, and SW-163s, are important secondary metabolites imparting antibiotic antitumor activity via DNA bisintercalation. Previously we have shown the production of echinomycin and triostin A in E. coli using our convenient and modular plasmid system to introduce these heterologous biosynthetic pathways into E. coli. However, we have yet to develop a novel biosynthetic pathway capable of producing bioactive unnatural natural products in E. coli. Here we report an identification of a new gene cluster responsible for the biosynthesis of SW-163s that involves previously unknown biosynthesis of (+)-(1S, 2S)-norcoronamic acid and generation of aliphatic side chains of various sizes via iterative methylation of an unactivated carbon center. Substituting an echinomycin biosynthetic gene with a gene from the newly identified SW-163 biosynthetic gene cluster, we were able to rationally re-engineer the plasmid-based echinomycin biosynthetic pathway for the production of a novel bioactive compound in E. coli.

Sesquiterpene dimer and trimer from Chloranthus japonicus

Abstract A novel sesquiterpene trimer, trishizukaol A, consisting of three lindenane units was isolated from the roots of Chloranthus japonicus . The structure was elucidated by 1D- and 2D-NMR methods. A structurally related sesquiterpene dimer was also found in the same plant.

Symmetric sesquiterpene dimer from Chloranthus serratus

Abstract A novel dimeric sesquiterpene having a C2-symmetric structure was isolated from the roots of Chloranthus serratus. The unique cyclic structure, including a 12-membered ring, was elucidated principally by 1D- and 2D-NMR methods and the stereochemistry was disclosed through detecting NOEs between equivalent protons by 13C-coupled HMQC-NOESY.

Iriomoteolide-3a, a Cytotoxic 15-Membered Macrolide from a Marine Dinoflagellate Amphidinium Species

A 15-membered macrolide, iriomoteolide-3a (1), with an allyl epoxide has been isolated from a marine benthic dinoflagellate Amphidinium sp. (strain HYA024), and the structure was assigned by detailed analyses of 2D NMR data. Relative and absolute configurations were elucidated on the basis of conformational studies of 1 and its acetonide (2) and modified Moshers method of 1, respectively. Iriomoteolide-3a (1) and the acetonide (2) exhibited potently cytotoxic activity against antitumor cells.

Seven acylated anthocyanins in blue flowers of Gentiana

Abstract Three novel anthocyanins, delphinidin 3,3′- di -O-β- d -glucoside -5-O-(6-O- caffeoyl -β- d -glucoside ) , delphinidin 3,3′- di -O-β- d -glucoside -5-O-(6-O-trans-p- coumaroyl -β- d -glucoside ) and delphinidin 3-O-β- d -glucoside -5-O-(6-O-trans-p- coumaroyl -β- d -glucoside ) , named albireodelphin A, B and C, respectively, were isolated from the blue flowers of Gentiana cv. Albireo, along with two known anthocyanins, gentiodelphin and gentiocyanin A. The complete structure of each anthocyanin was unambiguously determined by one- and two-dimensional NMR and other spectral methods. Two other novel anthocyanins, delphinidin 3-O-β- d -glucoside -5-O-(6-O- caffeoyl -β- d - glucoside )-3′-O-(6-O-trans-p- coumaroyl -β- d -glucoside ) and dephinidin 3-O-β- d -glucoside -5-O-(6-O-trans-p- coumaroyl -β- d -glucoside )-3′-O-(6-O- caffeoyl -β- d -glucoside ) , named albireodelphin D and E, respectively, were obtained as a mixture and the structures estimated by one- and two-dimensional NMR and other spectral methods.

4-Hydroxy-3-nitrophenylacetic and Sinapic Acids as Antibacterial Compounds from Mustard Seeds

A methanol extract from yellow mustard seeds had antibacterial activity against Escherichia coli, Salmonella enteritidis, and Staphylococcus aureus. Two compounds with such activity were isolated from the extract. By instrumental analysis, the compounds were identified as 4-hydroxy-3-nitrophenylacetic and sinapic acids. Examination of the structure-activity relationship showed that the hydroxyl and nitro groups of the first compound were involved in the activity against all three species. The two methoxyl groups and the hydroxyl group in sinapic acid were effective against E. coli and all of the substituents of the benzene ring were effective against S. enteritidis. The presence of the propenoic group of the second compound was effective against S. aureus.

Seven acylated anthocyanins in the blue flowers of Hyacinthus orientalis

Two novel anthocyanins, delphinidin 3-O-(6-O-cis-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta-D -glucoside) and petunidin 3-O-(6-O-trans-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta -D-glucoside) , were isolated from the blue flowers of Hyacinthus orientalis cv. Delft Blue. Five known acylated anthocyanins, namely, delphinidin 3-O-(6-O-trans-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-beta-D-gluco side), delphinidin 3-O-(6-O-trans-caffeoyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta-D- glucoside), delphinidin 3-O-(6-O-trans-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta -D-glucoside) , cyanidin 3-O-(6-O-trans-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta -D-glucoside) and pelargonidin 3-O-(6-O-trans-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta -D-glucoside) , were also isolated from these flowers. The complete structure of each compound was unambiguously determined by one- and two-dimensional NMR techniques.

Three acylated cyanidin glucosides in pink flowers of gentiana

Abstract Three novel anthocyanins, cyanidin 3-O-β- d -glucoside -5-O-(6-O- caffeoyl -β- d -glucoside ) , cyanidin 3-O-β- d -glucoside -5,3′- bis -O-(6-O- caffeoyl -β- d -glucoside ) and cyanidin 3-O-β- d -glucoside -5-O-(6-O-trans-p- coumaroyl -β- d -glucoside ) , gentiocyanin A, B and C, respectively, were isolated from pink flowers of gentian, along with a known anthocyanin, cyanidin 3-O-β- d -glucoside . The complete structure of each anthocyanin was unambiguously determined by 1D- and 2D-NMR and other spectral methods.