Takaaki Kubota

The Daphniphyllum alkaloids

Covering: 1966 to 2008About two hundred Daphniphyllum alkaloids have so far been isolated from thirteen species of the genus Daphniphyllum. This comprehensive review summarizes all the research into the isolation and structure elucidation of these alkaloids reported since investigations began in 1966. The structures of the Daphniphyllum alkaloids are classified based on six Daphniphyllum alkaloids (daphniphylline, secodaphniphylline, yuzurimine, daphnilactone A, daphnilactone B and yuzurine); there are also a number of newly found skeletons. The biosynthetic pathways, total syntheses, and bioactivities of the Daphniphyllum alkaloids are also described.

Total Synthesis and Biological Evaluation of Amphidinolide V and Analogues

The awesome power of metathesis is illustrated by a concise synthesis of the extremely scarce marine natural product amphidinolide V, which hinges on a sequence of ring-closing alkyne metathesis followed by intermolecular enyne metathesis with ethylene (see scheme). As a complete set of conceivable stereoisomers was prepared, the constitution and absolute configuration of this macrolide could be established and first insights into structure-activity relationships governing its cytotoxicity were obtained.A sequence of ring-closing alkyne metathesis followed by an intermolecular enyne metathesis of the resulting cycloalkyne with ethene was used to forge the macrocyclic skeleton and to set the vicinal exo-methylene branches characteristic for the cytotoxic marine natural product amphidinolide V (1). Comparison of the synthetic material with an authentic sample of this extremely scarce metabolite isolated from a dinoflagellate of the Amphidinium sp. eliminated any doubts about its structure and allowed the absolute configuration of amphidinolide V to be determined as 8R,9S,10S,13R. Moreover, the flexibility inherent to the underlying synthesis blueprint also opened access to a comprehensive set of diastereomers of 1 as well as to synthetic analogues differing from the natural lead in the lipophilic chains appended to the macrocyclic core. This set of designed analogues gave first insights into structure-activity relationships, which revealed that the stereostructure of the macrolactone is a highly critical parameter, whereas the examined alterations of the side chain did not diminish the cytotoxicity of the compounds to any notable extent.

Pyrinodemin A, a cytotoxic pyridine alkaloid with an isoxazolidine moiety from sponge Amphimedon sp

Abstract A novel cytotoxic pyridine alkaloid, pyrinodemin A (1), with a unique cis-cyclopent[c]isoxazolidine moiety has been isolated from the Okinawan marine sponge Amphimedon sp., and the structure was elucidated from 2D NMR data and EIMS fragmentation.

Colopsinol A, a Novel Polyhydroxyl Metabolite from Marine Dinoflagellate Amphidinium sp.

Colopsinol A (1), a novel polyhydroxyl compound, has been isolated from the cultured marine dinoflagellate Amphidinium sp., from which a number of cytotoxic macrolides, amphidinolides, have been obtained to date, and the gross structure of 1 was elucidated on the basis of extensive spectroscopic analyses including recent 2D NMR techniques of CH(2)-selected editing HSQC as well as FABMS/MS experiments and chemical means. Colopsinol A (1), C(71)H(119)O(25)SNa, is the first member of a new class of polyketide natural products possessing a gentiobioside moiety and a sulfate ester. The polyketide aglycon consisted of a C(56)-linear aliphatic chain with one exo-methylene and two methyl branches as well as two ketones, five hydroxyl groups, and a tetrahydropyran and two epoxide rings.

Bioactive macrolides and polyketides from marine dinoflagellates

Absolute stereochemistry of amphidinolides G and H, potent cytotoxic 27- and 26-membered macrolides, respectively, isolated from a marine dinoflagellate Amphidinium sp., was determined by X-ray diffraction analysis, synthesis of a degradation product, and chemical interconversion. Six new macrolides, amphidinolides H2~H5, G2, G3, and W, have been isolated from a marine dinoflagellate Amphidinium sp. (strain Y-42), and the structures were elucidated by 2D NMR data and chemical means. The structure-activity relationship of amphidinolide H-type macrolides for cytotoxicity was examined. The biosynthetic origins of amphidinolides B, C, H, J, T1, and W were investigated on the basis of 13C NMR data of 13C-enriched samples obtained by feeding experiments with [1-13C], [2-13C], and [1,2-13C2] sodium acetates in cultures of the dinoflagellates. Five novel long-chain polyhydroxyl compounds, colopsinols A~E, were obtained from the Amphidinium sp. (strain Y-5).

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.

Amphidinolide T5, a new 19-membered macrolide from a dinoflagellate and X-ray structure of amphidinolide T1

Abstract Amphidinolide T5 (1), a new 19-membered macrolide related to amphidinolide T1 (2), has been isolated from a marine dinoflagellate Amphidinium sp. The structure of 1 was elucidated on the basis of spectroscopic data and chemical means. The stereostructure of amphidinolide T1 (2) was confirmed by a single crystal X-ray diffraction analysis.

Absolute stereochemistry of amphidinolide E.

The absolute configurations at five chiral centers in amphidinolide Q (1), a cytotoxic 12-membered macrolide isolated from a marine dinoflagellate Amphidinium sp., were elucidated to be 4R, 7R, 9S, 11R, and 13R on the basis of NMR analyses and a modified Moshers method.

Nakijiquinones G-I, new sesquiterpenoid quinones from marine sponge.

Three new sesquiterpenoid quinones, nakijiquinones G-I (1-3), containing a different amino group derived from amino acids have been isolated from Okinawan marine sponges of the family Spongiidae, and the structures and relative stereochemistry of 1-3 were elucidated on the basis of the spectral data. Nakijiquinones G-I (1-3) showed modest cytotoxicity and inhibitory activity against HER2 kinase, while nakijiquinone H (2) exhibited antimicrobial activity.

Lyconadins D and E, and complanadine E, new Lycopodium alkaloids from Lycopodium complanatum

Three new Lycopodium alkaloids, lyconadins D (1) and E (2), and complanadine E (3), were isolated from the club moss Lycopodium complanatum. Lyconadin D (1) was the first example of fastigiatine-type alkaloid isolated from Lycopodium complanatum. The structures and relative stereochemistry of 1-3 were elucidated on the basis of spectroscopic data. Complanadine E (3) enhanced mRNA expression for NGF.