Absolute stereochemistry of citrinadins a and B from marine-derived fungus

[Structure: see text]. Citrinadin A (2) is a pentacyclic indolinone alkaloid isolated from the cultured broth of a fungus, Penicillium citrinum, which was separated from a marine red alga. The absolute stereochemistry of the pentacyclic core in 2 and its new congener, citrinadin B (1), was elucidated by analysis of the ROESY spectrum for the chlorohydrin derivative (3) of 1 as well as comparison of the electronic circular dichroism (ECD) spectra for 1 and 2 with those of known spirooxiindole alkaloids. On the other hand, the absolute configuration at C-21 bearing an epoxide ring was assigned as S by comparison of the vibrational circular dichroism (VCD) spectra of 1 with those of model compounds 2S- and 2R-2,3-epoxy-3,3-dimethyl-1-phenylpropan-1-one (4a and 4b, respectively).     

Absolute configuration of aflastatin A, a specific inhibitor of aflatoxin production by Aspergillus parasiticus

Aflastatin A (1) is a specific inhibitor of aflatoxin production by Aspergillus parasiticus. It has the novel structure of a tetramic acid derivative with a long alkyl side chain. The absolute configurations of 29 chiral centers contained in 1 were chemically elucidated in this study. First, four small fragment molecules were prepared from 1 or its methyl ether (2), and their absolute structures were assigned as N-methyl-D-alanine, (2S,4R)-2, 4-dimethyl-1,6-hexanediol dibenzoate, (R)-3-hydroxydodecanoic acid, and (R)-1,2,4-butanetriol tribenzoate. Next, an acyclic fragment molecule 3 with 13 chiral centers was obtained from 1 by NaIO(4) oxidation, and its relative stereochemistry was elucidated by J-based configuration analysis. By analyzing coupling constants of (3)J(H,H) and (2,3)J(C,H) and ROE data, the relative configuration of 3 was verified. Finally, by further J-based configuration analysis using a fragment molecule 7 prepared from 2 with 28 chiral carbons, all relative configurations in the alkyl side chain of 1 were clarified. By connecting these relative configurations with the absolute configurations of first four fragment molecules, the absolute stereochemistry of 1 was fully determined.     

Ammosamide D, an oxidatively ring opened ammosamide analog from a marine-derived Streptomyces variabilis

Ammosamide D (1), an oxidized analog of the ammosamide family, was isolated from a marine-derived Streptomyces variabilis. Pyrroloquinoline containing alkaloids are a growing class of natural products, with 1 being the first example of an oxidized analog resulting in a 5,6-dioxo-5,6-dihydroquinoline ring system. Attempts at chemical conversion of ammosamide B to ammosamide D revealed that a strong chemical oxidant is required. Ammosamide D has modest cytotoxicity to the MIA PaCa-2 pancreatic cancer cell line.     

Piperazimycins: cytotoxic hexadepsipeptides from a marine-derived bacterium of the genus Streptomyces

Three potent cancer cell cytotoxins, piperazimycins A-C (1-3), have been isolated from the fermentation broth of a Streptomyces sp., cultivated from marine sediments near the island of Guam. The structures of these cyclic hexadepsipeptides were assigned by a combination of spectral, chemical, and crystallographic methods. The piperazimycins are composed of rare amino acids, including hydroxyacetic acid, alpha-methylserine, gamma-hydroxypiperazic acid, and gamma-chloropiperazic acid. The novel amino acid residues 2-amino-8-methyl-4,6-nonadienoic acid and 2-amino-8-methyl-4,6-decadienoic acid were found as components of piperazimycins A and C, respectively. When screened in the National Cancer Institute's 60 cancer cell line panel, piperazimycin A exhibited potent in vitro cytotoxicity toward multiple tumor cell lines with a mean GI50 of 100 nM.     

Azamerone, a terpenoid phthalazinone from a marine-derived bacterium related to the genus Streptomyces (Actinomycetales)

A novel meroterpenoid, azamerone, was isolated from the saline culture of a new marine-derived bacterium related to the genus Streptomyces. Azamerone is composed of an unprecedented chloropyranophthalazinone core with a 3-chloro-6-hydroxy-2,2,6-trimethylcyclohexylmethyl side chain. The structure was rigorously determined by NMR spectroscopy and X-ray crystallography. A possible biosynthetic origin of this unusual ring system is proposed. [structure: see text]     

Absolute configuration of sebiferine

Absolute configuration of sebiferine has been determined.     

5-Demethoxyfumagillol, a potent angiogenesis inhibitor isolated from Aspergillus fumigatus

A novel angiogenesis inhibitor, 5-demethoxyfumagillol (1), was obtained by isolation, purification and saponification of cultured broth of Aspergillus fumigatus. The structure was assigned as (3R,4R,6R)-4-[(2R,3R)-2-methyl-3-(3-methyl-but-2-enyl)-oxiranyl]-1-oxa-spiro[2,5]octan-6-ol (1) by spectroscopic analysis and confirmed by independent synthesis from fumagillol (3). In addition, 6-O-(chloroacetylcarbamoyl)-5-demethoxyfumagillol (7) showed a potential anti-angiogenic activity in CAPE cells in vitro.     

Absolute configuration of fucoxanthin

The common natural isomer of the allenic carotenoid fucoxanthin has the 3S,5R,6S,3′S,5′R,6′R configuration.     

Absolute configuration of scyphostatin

[reaction: see text] The absolute configuration of the side chain of scyphostatin (1) has been established. The chemical degradation of 1 gave 4 and 9, which correspond to the C7'-C12' and C13'-C16' fragments of the natural products, respectively. The spectroscopic data and [alpha]D values of both compounds were compared to those of authentic samples. The results show that the absolute configuration of 1 is 8'R,10'S,14'R.     

Absolute structure, biosynthesis, and anti-microtubule activity of phomopsidin, isolated from a marine-derived fungus Phomopsis sp.

The absolute configuration of phomopsidin, a marine-derived fungal metabolite from Phomopsis sp. isolated at Pohnpei, was determined by the exciton chirality method as 6S, 7S, 8S, 11S, 12R, and 15R. The biosynthetic study using ¹³C-labeled precursors revealed the origin of all carbon atoms in phomopsidin, which was built by nine acetates and three methyl groups from l-methionine. Inhibitory activities of phomopsidin and its Me ester derivative against microtubule assembly were examined together with the structurally related compounds MK8383, solanapyrones, and tanzawaic acids. Phomopsidin and its (16Z)-isomer (MK8383) showed anti-microtubule activity at IC₅₀ of 5.7 and 8.0 μM, respectively, while the Me ester and other compounds were not active at 100 μM.     

Secondary metabolites from marine-derived Streptomyces antibioticus strain H74-21

A new secondary metabolite, (2S,3R)-l-threonine, N-[3-(formylamino)-2-hydroxybenzoyl]-ethyl ester (streptomyceamide C, 1), together with four known compounds 1, 4-dimethyl-3-isopropyl-2,5-piperidinedione (2), cyclo-((S)-Pro-8- hydroxy-(R)-Ile (3), cyclo-((S)-Pro-(R)-Leu (4), and seco-((S)-Pro-(R)-Val) (5), were isolated from the EtOH extract of the fermented mycelium of the marine-derived streptomycete strain H74-21, which was isolated from sea sediment in a mangrove site. The structure of the new compound was established on the basis of its spectroscopic data, including 1D and 2D NMR, HR-TOF-MS. Their antifungal activities against Candida albicans and cytotoxicities against human breast adenocarcinoma cell line MCF-7, human glioblastoma cell line SF-268 and human lung cancer cell line NCI-H460 were tested. Compounds 1 only displayed cytotoxicity against human breast adenocarcinoma cell line MCF-7 with the IC₅₀ value of 27.0 μg/mL. However, compounds 1–5 do not show antifungal activities at the test concentration of 1 mg/mL, and 2–5 have no cytotoxicities at the test concentration of 50 μg/mL.     

Absolute configuration of myrobotinol, new fused-hexacyclic alkaloid skeleton from Myrioneuron nutans

Myrobotinol (1) was isolated from the leaves of Myrioneuron nutans (Rubiaceae) and its structure determined from spectral data, including mass spectrometry and 2D NMR. This compound presents a new hexacyclic alkaloid skeleton including a 1,3-oxazine and aminal functionality. The absolute configuration of myrobotinol was established by using Mosher's method. A plausible biosynthetic pathway starting from L-lysine via Delta-piperideine was proposed for this hexacyclic alkaloid.     

Halichoblelides B and C,potent cytotoxic macrolides from a Streptomyces species separated from a marine fish

Halichoblelide B (1) and C (2), novel macrolides with potent cytotoxicity against tumor cells in culture, have been isolated from a strain of Streptomyces hygroscopicus originally derived from the marine fish Halichoeres bleekeri, and their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and chemical transformations. These compounds exhibited significant cytotoxicity against human cancer cell lines.     

Absolute configuration of crotsparine,crotsparinine and sparsiflorine

Absolute configurations of crotsparine, crotsparinine and sparsiflorine have been determined.