Iriomoteolide-13a,a cytotoxic 22-membered macrolide from a marine dinoflagellate Amphidinium species

Iriomoteolide-13a (1) has been isolated from a benthic dinoflagellate Amphidinium sp. (strain KCA09053) as a new 22-membered macrolide containing one hexahydrofuro[3,2-b]furan ring, one tetrahydropyran ring, two tetrahydrofuran rings, three one-carbon branches, and three hydroxyl groups including two hemiketals. The structure of 1 was assigned on the basis of a detailed 2D NMR analysis. Compound 1 exhibited cytotoxic activity against human cervix adenocarcinoma HeLa cells (IC₅₀: 0.5 μg/mL).     

Eight new diterpenoids from soft coral Cespitularia hypotentaculata

Chemical investigation of the soft coral Cespitularia hypotentaculata resulted in the isolation of eight new diterpenes, cespihypotins E-L (1-8). The new metabolites comprise of six verticillene-type diterpenes, one cespitularane derivative, and one derivative with 14-membered lactone ring. The structures were determined through detailed spectroscopic analyses, especially high resolution ESIMS and 2D NMR techniques. The relative stereochemistry was deduced from NOESY spectrum and application of Mosher's ester technique. Immunomodulatory and antiviral activities of 1-8 were tested and evaluated. The biogenetic pathways for 1-8 were also proposed.     

Structures of new alkaloids sessilifoliamides A-D from Stemona sessilifolia

Four new Stemona alkaloids, sessilifoliamides A-D (1-4), were isolated from the roots of Stemona sessilifolia, along with five known alkaloids, stenine (5), 2-oxostenine (6), stemoninoamide (7), tuberostemonone (8), and neotuberostemonol (9). The structures and absolute configurations of the new alkaloids were determined by the spectral studies (HRMS, IR, ¹H, ¹³C, and 2D NMR), single-crystal X-ray analyses, and chemical correlations. The absolute configuration of 7 was also determined by the modified Mosher's method.     

Proanthocyanidin glycosides from the leaves of Quercus ilex L. (Fagaceae)

From the polar extracts of the leaves of Quercus ilex L., two new proanthocyanidin glycosides, namely afzelechin-(4α→8)-catechin-3-O-β-glucopyranoside (1) and afzelechin-(4α→8)-catechin-3-O-α-rhamnopyranoside (2), were isolated in addition to catechin (3), proanthocyanidin B₃ (4), prodelphinidin C (5), dehydrodicatechin A (6), quercetin (7) and six known flavonol glucosides with their acylated derivatives (8-13) and ellagic acid (14). The structures of all isolated compounds were established by spectroscopic means, mainly 1D and 2D NMR, as well as LC/MS and HR-MS spectrometric analyses. The absolute configuration of compound 1 was determined by CD measurements. The proanthocyanidin glycosides are especially interesting, as they possess the sugar in the upper unit of the dimer, which is rare for this type of compounds.     

Rumphellatin A, the first chloride-containing caryophyllane-type norsesquiterpenoid from Rumphella antipathies

A novel chloride-containing 14C norsesquiterpenoid, rumphellatin A (1), was isolated from the Formosan gorgonian coral Rumphella antipathies. The structure of metabolite 1 was determined on the basis of spectral data analysis and the configuration of 1 was further supported by molecular mechanics calculations. Rumphellatin A (1) showed activity against Gram-negative bacteria.     

Jiadifenlactone A,a novel diseco-prezizaane-type sesquiterpenoid from the fruits of Illicium jiadifengpi

Jiadifenlactone A (1), the first example of cleavage of bond [4, 9] of the seco-prezizaane-type sesquiterpenoid with a unique 9-membered ring moiety, together with its biosynthetic related compound 2, were isolated from the fruits of Illicium jiadifengpi. The structure of 1 and its relative configuration were determined by spectroscopic methods and single-crystal X-ray diffraction analysis. The inhibitory rates of compound 1 on the HBeAg and HBsAg expressions were 37.91 ± 2.78% and 17.21 ± 3.78%, respectively.     

Enantioselective synthesis of aurisides A and B, cytotoxic macrolide glycosides of marine origin

The enantioselective synthesis of aurisides A and B, macrolide glycosides of marine origin, was achieved by a convergent approach. The C1-C9 segment 4 was prepared from (R)-pantolactone, and the C10-C17 segment 14 was synthesized from (R)-glycidyl trityl ether. The Nozaki-Hiyama-Kishi reaction between 4 and 14 and subsequent reactions gave seco acid 10, which was converted into the aglycon (3) of aurisides by construction of the 14-membered lactone and bromine-substituted conjugated diene. The glycosylation reaction of the aglycon provided aurisides A and B.     

Structural revision and absolute configuration of lateritin

‘Lateritin’ (1), a morpholine-2,5-dione (depsipeptide), was reinvestigated for its structure and absolute configuration. On the basis of thorough 1D and 2D NMR and mass spectrometrical analyses, the structure of 1 was revised to be identical with beauvericin (8) and confirmed that beauvericin (8) is the trimeric lactone of ‘lateritin’ (1). The absolute configuration was determined by acidic hydrolysis, followed by application of Marfey’s method, menthyl ester derivatization, and GC–MS analysis. In addition, the specific optical rotation values of the hydrolysis products were compared with those of available standards.     

Asymmetric synthesis of a diastereomer of the structure proposed for amphidinolide A and the determination of its absolute configuration

An asymmetric synthesis of a diastereomer (2) of the structure (1) proposed for amphidinolide A, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp., has been accomplished. The absolute configuration of amphidinolide A was established as 3 from comparison of NMR data, HPLC analysis, and [α]_D values of amphidinolide A, and comparison with the synthetic diastereomers 2 and 3, the latter of which was synthesized previously by Trost's group.     

A convergent synthesis of the macrolide core of migrastatin

We describe an efficient synthesis of the 14-membered macrolide core 2 of migrastatin via key intermediate 3 employing a diastereoselective aldol condensation, Lewis acid mediated diastereoselective addition and an exclusive (Z)-olefination sequence. Yamaguchi esterification of the key intermediate 3 followed by ring-closing metathesis (RCM) produced macrolide 2 with high selectivity and good yield.     

Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia: isolation, structure determination, synthesis, and biological activity

The bioassay-guided fractionation of the cytotoxic constituents of the Japanese sea hare Dollabella auricularia led to the isolation of aurilide (1), a 26-membered cyclodepsipeptide. The gross structure of 1 was established by spectroscopic analysis including 2D NMR techniques. The absolute stereostructure was determined by chiral HPLC analysis of acid hydrolysates of 1 and by the enantioselective synthesis of a degradation product arising from a dihydroxylated fatty acid portion. The enantioselective synthesis of 1 was achieved in 12% overall yield (16 steps) and confirmed the absolute stereostructure of 1. The cytotoxicity of 1 was evaluated using a synthetic sample, which was found to exhibit potent cytotoxicity against HeLa S₃ cells with an IC₅₀ of 0.011 μg/mL. Further biological and pharmacological studies of 1 have been carried out by using synthetic 1.     

Determination of absolute configuration of C14−C23 fragment in symbiodinolide

The degradation product C14−C23 2 was obtained using ethenolysis with the 2nd-generation Hoveyda-Grubbs catalyst from 62-membered lactone in symbiodinolide (1). The absolute configurations of three chiral centers in fragment 2 were assigned as 17R, 18R, and 21R by a combination of J-based configuration analysis and the Mosher-Riguera method.     

Eight novel serine proteases inhibitors from a water bloom of the cyanobacterium Microcystis sp.

Eight new secondary metabolites, micropeptin MM836 (1), micropeptin MM850 (2), micropeptin MM916 (3), micropeptin MM932 (4), micropeptin MM978 (5), anabaenopeptin MM823 (6), anabaenopeptin MM850 (7), and anabaenopeptin MM913 (8), as well as the known anabaenopeptin B (9) were isolated from the hydrophilic extract of the cyanobacterium Microcystis sp. that was collected from a fishpond in Kibbutz Ma’agan Michael, Israel, in September 2006. The structure of the pure natural products was established by spectroscopic methods including 1D and 2D NMR, UV, and MS techniques. The absolute configuration of the chiral centers of the compounds was determined using Marfey’s method. The inhibitory activity of the compounds was determined against the serine proteases, trypsin, chymotrypsin, thrombin and elastase.     

Kendarimide A, a novel peptide reversing P-glycoprotein-mediated multidrug resistance in tumor cells, from a marine sponge of Haliclona sp.

A novel modulator of multidrug resistance (MDR) in tumor cells, kendarimide A (1), was isolated from an Indonesian marine sponge of Haliclona sp. Compound 1 reversed MDR in KB-C2 cells mediated by P-glycoprotein (P-gp) at a 6 μM concentration, and the chemical structure of 1 was characterized to be a linear peptide composed of N-methylpyroglutamic acid (pyroMeGlu), N-methylated eight-membered cysteinyl-cysteine (ox-[MeCys-MeCys]) together with many N-methyl amino acid residues. The amino acid sequence of 1 was determined by 2D NMR and FAB MS analysis. The absolute configuration of the amino acid residues in 1 except for the MeCys part was determined to be l-form respectively, based on interpretation of the HPLC analysis of Marfey's derivatives of the hydrolysates of 1 and the synthetic method for the pyroMeGlu residue.     

Shimalactone A, a novel polyketide, from marine-derived fungus Emericella variecolor GF10

Shimalactone A (1), a novel polyketide having bicyclo[4.2.0]octadiene and oxabicyclo[2.2.1]heptane units, was isolated from a cultured marine fungus of Emericella variecolor GF10. The stereo structure of 1 was deduced from 2D NMR and X-ray crystallographic analyses of 1 and its derivatives. The absolute structure of 1 was determined by application of the CD allylic benzoate rule to the benzoate derivative of 1. Shimalactone A (1) induced neuritogenesis at 10 μg/mL against neuroblastoma Neuro 2A cells.     

Synthesis of E-deoxypukalide, and its biomimetic conversion into deoxypseudopterolide by photochemical ring contraction involving a 1,3-allylic shift

Irradiation of a solution of synthetic Z-deoxypukalide 10 in acetonitrile (Pyrex; 400 W Hg lamp) resulted in isomerisation, leading to E-deoxypukalide 12, which was isolated recently from the octocoral Leptogorgia spp. Further irradiation of 12, or prolonged irradiation of 10, then gave the ring-contracted product, deoxypseudopterolide 1 (>90%) found in octocorals of the genera Pseudopterogorgia and Leptogorgia. The contraction of the 14-membered rings in 10 and 12 to the 12-membered ring as 1, occurs by way of photochemical [1,3]-sigmatropic rearrangement.     

Velutabularins A-J, phragmalin-type limonoids with novel cyclic moiety from Chukrasia tabularis var. velutina

Velutabularins A-J, ten novel phragmalin-type limonoids, were isolated from the stem bark of Chukrasia tabularis var. velutina. In structures of 1-6, the tetrahydrofuran ring from dehydration of OH-15 and OH-17, ring C and 13/14/18-cyclopropanyl moiety formed an unprecedented 8-oxatricyclo[4,3,1^1,6]decane. Compounds 7-10 are derivates of 1-6 opening the tetrahydrofuran ring. All of these compounds possess a novel C-16/C-30 δ-lactone ring, which were reported in phragmalins rarely. The structures of these novel compounds were elucidated based on extensive 1D and 2D spectroscopic analysis. The absolute configuration of 5 and 9 were determined by the calculated electronic circular dichroism (ECD) method. The anti-inflammatory activities of major compounds (2, 4, 5, 9) were evaluated for inhibitory activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in macrophage (RAW264.7) cell line.     

Absolute stereostructure of Andirolides A-G from the flower of Carapa guianensis (Meliaceae)

A new gedunin, three new mexicanolides and three new phragmalin-type limonoids named Andirolides A (1), B (2), C (3), D (4), E (5), F (6), and G (7) were isolated from oil of the flower of Carapa guianensis Aublet (Meliaceae). Their absolute stereostructures were determined by 2D NMR and CD spectra, and single-crystal X-ray analysis, and all compounds were confirmed to have the C-17βH configuration. Considering the similarity in CD spectra between Andirolide G (7) and the xyloccensins reported by Wu, we concluded that the structures of xyloccensins should be revised so as to have the absolute configuration of 17R.     

New microviridins from a water bloom of the cyanobacterium Microcystis aeruginosa

Three new microviridins namely, SD1684 (1), SD1634 (2), and SD1652 (3), were isolated from the hydrophilic extract of Microcystis aeruginosa. The planar structures of compounds 1-3 were determined by homonuclear and inverse-heteronuclear 2D-NMR techniques as well as by high-resolution mass spectrometry. The absolute configuration of the asymmetric centers was studied using Marfey's method for HPLC. Compounds 1-3 contain l-threo-β-hydroxy aspartic acid as a building block of the peptide chain. This is the first example where microviridins contain non-proteinogenic amino acid in their structure. Compound 2 is a mild serine protease inhibitor.     

Briaexcavatolides X-Z, three new briarane-related derivatives from the gorgonian coral Briareum excavatum

Three new polyoxygenated briarane-type diterpenoids, briaexcavatolides X-Z (1-3), have been isolated from the gorgonian coral Briareum excavatum. The structures, including the relative configurations of briaranes 1-3, were elucidated by spectroscopic methods, particularly in 1D and 2D NMR experiments. The configuration of briarane 1 was further supported by molecular mechanics calculations.