Fumito Ishibashi

Insecticidal 1H-cyclopentatetrahydro[b]benzofurans from Aglaia odorata

Abstract Bioassay-directed separation of a methanolic extract of the leaves of Aglaia odorata led to the isolation of a known cyclopentatetrahydrobenzofuran, rocaglamide, along with its congeners, desmethylrocaglamide, methyl rocaglate and rocaglaol. The structures of the three new compounds were determined on the basis of spectroscopic evidence and by comparisons of their 1H NMR data with those of rocaglamide. Rocaglamide and methyl rocaglate exhibited potent insecticidal activity both through growth inhibition and contact toxicity to the variegated cutworm, Peridroma saucia.

Anticancer alkaloid lamellarins inhibit protein kinases.

Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition of topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dual-specificity tyrosine phosphorylation activated kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good correlation is observed between the effects of lamellarins on protein kinases and their action on cell death, suggesting that inhibition of specific kinases may contribute to the cytotoxicity of lamellarins. Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors.

Algicidal activity of polyunsaturated fatty acids derived from Ulva fasciata and U. pertusa (Ulvaceae, Chlorophyta) on phytoplankton

Isolation of algicidal compounds from Ulva fasciata revealed that the algicidal substances were the polyunsaturated fatty acids (PUFAs) as hexadeca-4,7,10,13-tetraenoic acid (HDTA) C16:4 n-3, octadeca-6,9,12,15-tetraenoic acid (ODTA) C18:4 n-3, α-linolenic acid (ALA) C18:3 n-3 and linoleic acid (LA) C18:2 n-6. The fatty acid composition of four species of Ulvaceae (U. fasciata, U. pertusa, U. arasakii and U. conglobota) was analyzed by capillary gas chromatography to investigate the relationship with the algicidal activity. The results indicate that highly algicidal species, U. fasciata and U. pertusa, showed higher contents of C16:4 n-3, C18:3 n-3, and C18:4 n-3. Concentrations of these PUFAs released from the seaweed in the culture medium were also analyzed. These PUFAs were found to be significantly active against Chattonella antiqua, C. marina, Fibrocapsa japonica, Heterosigma akashiwo, Karenia mikimotoi, moderately effective against Heterocapsa circularisquama, Prorocentrum minimum, P. sigmoides, Scrippsiella trochoidea, whereas low effective against Alexandrium catenella and Cochlodinium polykrikoides. It is suggested that the PUFAs are useful mitigation agents to remove several harmful effects without causing detrimental effects on surrounding marine living organisms.

Design and synthesis of lamellarin D analogues targeting topoisomerase I.

A general synthetic route to rationally designed lamellarin D analogues, 1-dearyllamellarin D (1) and 1-substituted 1-dearyllamellarin D (2), has been developed. The key pentacyclic intermediate 22 was prepared by palladium-catalyzed direct arylation of 12, which in turn was synthesized via C-2-selective lithiation of 15 followed by palladium-catalyzed cross-coupling as the key reactions. Compound 22 was converted to a wide range of C-1-substituted analogues 2 via regioselective electrophilic substitution and palladium-catalyzed cross-coupling reactions.

Short and flexible route to 3,4-diarylpyrrole marine alkaloids: syntheses of permethyl storniamide A, ningalin B, and lamellarin G trimethyl ether

Abstract A highly efficient route to 3,4-diarylpyrrole marine alkaloids has been developed using Hinsberg-type pyrrole synthesis and palladium-catalyzed Suzuki cross-coupling of the 3,4-dihydroxypyrrole bis-triflate derivatives as key reactions. Based on this approach, formal syntheses of permethyl storniamide A and ningalin B, and a total synthesis of lamellarin G trimethyl ether have been achieved.

Total Syntheses of Lamellarin D and H. The First Synthesis of Lamellarin-Class Marine Alkaloids

Abstract Total syntheses of marine polyaromatic alkaloids, lamellarin D ( 1 ) and H ( 2 ), are described. The pentacyclic lamellarin ring system was constructed by N -ylide mediated pyrrole ring formation and subsequent lactonization of 4 obtained by an assembly of known benzylisoquinoline 5 , benzoate 6 and ethyl bromoacetate.

Isolation and Structure Determination of Algicidal Compounds from Ulva fasciata

Thirty-seven species of seaweeds including 10 Chlorophyta, 13 Phaeophyta, and 14 Rhodophyta collected from the coast of Nagasaki Prefecture, Japan, were screened for algicidal activity against the red-tide phytoplankton Heterosigma akashiwo. The green alga Ulva fasciata (Ulvaceae, Chlorophyta) showed the strongest algicidal activity among the seaweeds tested. Bioassay-guided fractionation of the methanol extract of U. fasciata led to isolation of three algicidal compounds whose structures were determined to be hexadeca-4,7,10,13-tetraenoic acid (HDTA), octadeca-6,9,12,15-tetraenoic acid (ODTA), and α-linolenic acid on the basis of spectroscopic information. These polyunsaturated fatty acids (PUFAs) showed potent algicidal activity against H. akashiwo (LC50 1.35 μg/ml, 0.83 μg/ml, and 1.13 μg/ml for HDTA, ODTA, and α-linolenic acid, respectively), and the result demonstrated the potential of these PUFAs for practical harmful algal bloom control.

New synthetic approach to pyrroloiminoquinone marine alkaloids. Total synthesis of makaluvamines A, D, I, and K

A new entry into pyrroloiminoquinone marine alkaloids, makaluvamines, has been developed. The key 1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline intermediates 11 and 18 were prepared by aryne-mediated cyclization of the 4-chloro-6-methoxytryptamine derivatives 10 and 17, respectively. The requisite substituents at the indole 4- and 3-positions of 10 and 17 were efficiently assembled by sequential use of directed lithiation of 1-triisopropylsilyl-6-methoxygramine (6) and fluoride ion-induced elimination-addition of the methiodide of 4-chloro-1-triisopropylsilyl-6-methoxygramine (7) as key reactions.

Synthesis and absolute configuration of the insecticidal sesquilignan (+)-HAEDOXAN a in honour of professor G. H. Neil Towers 75th birthday

Abstract The insecticidal neolignan, (+)-haedoxan A, was synthesized from ( S )-(+)- β -vinyl- γ -butyrolactone and ( 2R,3R )-(+)-6-formyl-7-methoxy-3-methoxymethyl-2-(3,4-methylenedioxyphenyl)-1,4-benzodioxane, and its absolute configuration was unequivocally established as 1S,2R,5R,6S,2″R,3″R .

A concise total synthesis of (±)-cis-and (±)-trans-clavicipitic acids by combinational use of directed lithiation and flouride ion-induced elimination-addition reaction of 1-(triisopropylsilyl)gramine derivatives

Abstract A six-step total synthesis of (±)-clavicipitic acid (1) from 1-(triisopropylsilyl)gramine (2) was achieved by combinational use of 4-selective lithiation of 2 and flouride ion-induced elimination-addition reaction of 4-[(E)-3-hydroxy-3-methyl-1-butenyl]-1-(triisopropylsilyl)gramine (7) as key reactions. Separation of cis- and trans-diastereomers (1a and 1b) were easily accomplished by simple fractional crystallization and column chromatography. The overall yields of 1a and 1b from 2 were 21% and 17%, respectively.