Chemistry of renieramycins. Part 7: Renieramycins T and U, novel renieramycin-ecteinascidin hybrid marine natural products from Thai sponge Xestospongia sp.

Two new bistetrahydroisoquinoline marine natural products, renieramycins T (1) and U (2), were isolated from the Thai blue sponge Xestospongia sp. and their structures were elucidated by comparing spectral data with those of renieramycin M (3a) and ecteinascidin 770 (4a). These compounds are the first reported examples of novel ecteinascidin-renieramycin hybrid natural products. Renieramycin T (1) showed strong cytotoxicity to several human cancer cell lines, its IC₅₀ values ranging from 4.7 to 98 nM.     

Chemistry of renieramycins. Part 11: Total synthesis of (±)-cribrostatin 4

A 19-step synthesis of (±)-cribrostatin 4 (1) from readily available piperazine-2,5-dione derivative 6 is described. The synthesis features the concise construction of a pentacyclic framework, followed by the base-catalyzed epimerization of the C-1 stereo center of aldehyde (11). The results of cytotoxicity studies are also presented.     

Efficient and stereoselective installation of isoquinoline: formal total synthesis of cortistatin A

The highly stereoselective attachment of isoquinoline onto the steroidal framework of cortistatin A has been achieved. Our strategy features a Ce-mediated nucleophilic addition of an isoquinoline unit to the sterically congested ketone followed by formation of the phenyl thiocarbamate, and subsequent stereoselective radical reduction. The new method results in a formal total synthesis of cortistatin A.     

Chemistry of renieramycins. Part 9: Stereocontrolled total synthesis of (±)-renieramycin G

A 25-step stereocontrolled total synthesis of (±)-renieramycin G (1g) from readily available 2-hydroxy-3-methyl-4,5-dimethoxybenzaldehyde (3) is described. This synthesis features the concise construction of the pentacyclic framework using the stereoselective Pictet-Spengler type cyclization reaction of lactam (14) with ethyl diethoxyacetate, followed by the base-catalyzed isomerization of the C-1 stereo center.     

Chemistry of renieramycins. Part 6: Transformation of renieramycin M into jorumycin and renieramycin J including oxidative degradation products, mimosamycin, renierone, and renierol acetate

The transformation of renieramycin M (1m) into renieramycin J (1j) and jorumycin (2) is presented along with the results of antiproliferative assay data. The chemical stability and the oxidative degradation of 2 and renieramycin E (1e) to generate simple isoquinoline alkaloids, such as mimosamycin (7), renierol acetate (12), and renierone (8) are also described.     

Biselides A-E: novel polyketides from the Okinawan ascidian Didemnidae sp.

Five new polyketides, biselides A (1), B (2), C (3), D (4), and E (5), were isolated from the Okinawan ascidian Didemnidae sp. Their structures were determined by spectroscopic analysis. Biselides A (1), B (2), and C (3) showed cytotoxicity against human cancer cells NCI-H460 and MDA-MB-231.     

New cytotoxic spongian diterpenes from the sponge Dysidea cf. arenaria

Seven new (1-7) and three known (8-10) spongian-class diterpenes have been isolated from the sponge Dysidea cf. arenaria collected in Okinawa. Compound 6 was also isolated from the nudibranch Chromodoris kuniei. The structures of the new entities were elucidated by spectroscopic analyses. Three of the new spongians (2, 6, and 7) showed cytotoxicity against NBT-T2 rat bladder epithelial cells.     

Synthesis of the common left-half part of pectenotoxins

The common left-half [C31-C33(OC1-C7)-C40] part of pectenotoxins has been synthesized convergently from the C31-C35, C36-C40, and C1-C7 parts. The C31-C35 part, prepared via a new route shorter than our previous route, was coupled with the C36-C40 part through reductive lithiation and addition reactions to give an adduct stereoselectively, which was converted to a cyclic acetal corresponding to the C31-C40 part. The left-half was synthesized by a three-step process including esterification of the C31-C40 part with the C1-C7 part.     

Total syntheses of (+)-spiculoic acid A and (+)-zyggomphic acid, new marine natural products of polyketide origin

The total syntheses of both natural (+)-spiculoic acid A and (+)-zyggomphic acid, new cytotoxic marine natural products of polyketide origin, have been accomplished for the first time. These syntheses were achieved by the highly stereoselective and high-yielding intramolecular Diels-Alder reaction of a functionalized (E,E,E)-2,7,9-dodecanal derivative to construct the core tetrahydroindan-2-one skeleton. A stereocongener of (+)-spiculoic acid A, i.e., the (2R,5S,6R)-isomer, was also synthesized. The details of these total syntheses are described.     

Two efficient four-step routes to marine toxin tanikolide

We have presented two facile four-step syntheses of (±)-tanikolide from ethyl 2-oxocyclopentanecarboxylate. The overall chemical yields of the two sequences reached as high as 76 and 85%, respectively. The first strategy involved alkylation, Baeyer-Villiger reaction, saponification, and reduction/lactonization. The second approach for synthesizing tanikolide took advantage of the same intermediate, the alkylated ketoester 2, which was converted to the target molecule in such three steps as deethoxycarbonylation, hydroxymethylation, and Baeyer-Villiger reaction. Our strategies are advantageous because of their high yields and suitability for the preparation of 1 in multigram or larger quantities.     

Solid-phase synthesis of lamellarins Q and O

An efficient solid phase synthesis of the pyrrole-based alkaloids lamellarins Q and O using Merrifield resin and N-protected methyl 3,4-dibromopyrrole-2-carboxylate as a scaffold is described.     

The application of vinylogous iminium salt derivatives to an efficient relay synthesis of the pyrrole containing alkaloids polycitone A and B

A new and efficient relay synthesis of the marine natural products polycitone A and B is described. The new strategy relies on the formation of 2,4-disubstituted pyrroles from a vinamidinium salt followed by electrophilic substitution at the 5-position of the pyrrole and Suzuki coupling at the 4-position to produce the tetrasubstituted heterocycle efficiently and with complete control of regiochemistry.     

Total synthesis of (+)-spiculoic acid A

The total synthesis of natural (+)-spiculoic acid A, a new cytotoxic marine natural product of polyketide origin, has been accomplished for the first time. The key step of the total synthesis was a stereoselective and high-yielding intramolecular Diels-Alder reaction of a highly functionalized (E,E,E)-2,7,9-dodecanal derivative for the construction of the core tetrahydroindan-2-one skeleton.     

Stereoselective synthesis of the cyclic ether core of (+)-laurenyne

A concise enantioselective synthesis of the cyclic ether core of the marine natural product (+)-laurenyne has been accomplished using ring-closing metathesis for medium-ring construction.     

New cyclic depsipeptides from the green alga Bryopsis species; application of a carboxypeptidase hydrolysis reaction to the structure determination

New cyclic depsipeptides, kahalalides P (1) and Q (2), were isolated from the Hawaiian green alga Bryopsis sp. The sequential positions of the dl anti-podal amino acids were determined by a carboxypeptidase hydrolysis reaction. This enzymatic method will be applicable to the structure determination of other non-ribosomal peptides. The absolute chemistry of 3-hydroxy-9-methyldecanoic acid in kahalalides P and Q were determined by the recently introduced convenient Mosher ester procedure.     

Capillary electrophoresis with LED-induced native fluorescence detection for determination of isoquinoline alkaloids and their cytotoxicity in extracts of Chelidonium majus L

In this study, we introduced a simple and sensitive method of capillary electrophoresis with ultraviolet light-emitting diode-induced native fluorescence (UV-LEDIF) detection for the determination of isoquinoline alkaloids in extracts of Chelidonium majus L. Samples were extracted with acidic methanol and the extracts were directly analysed by CE. Simultaneous determination of protopine, chelidonine, coptisine, sanguinarine, allocryptopine, chelerythrine and stylopine was performed in 20mM phosphate buffer (pH 3.1). The baseline separation of these alkaloids was finished within 20 min. As these alkaloids have native fluorescence, they were directly detected using the commercially available UV light emitting diode without troublesome fluorescent derivatisation. Satisfactory LOD values were obtained for the studied compounds considering their appearance in natural extracts. Lower limits of detection were 0.05 μg/mL for protopine, 0.06 μg/mL for stylopine and allocryptopine, 0.07 μg/mL for chelidonine, 0.22 μg/mL for sanguinarine, 1.7 μg/mL for chelerythrine and 5.5 μg/mL for coptisine. The developed method was successfully applied to determine the contents of seven alkaloids in the aerial parts of Chelidonium majus L, which varied from 0.025 to 0.763% (w/w). Also, to demonstrate the potential of the proposed CE method, an estimation of the cytotoxic properties of selected Celandine alkaloids in a natural extract was carried out.     

Preparation, properties and cytotoxicity evaluation of a biodegradable polyester elastomer composite

Multi-walled carbon nanotube (MWCNT)/poly(glycerol–sebacate–citrate) (PGSC) elastomer composite were prepared and their morphologies, compositions, glass transition temperatures, mechanical properties, water absorption, biodegradation and cytotoxicity were investigated. Results showed that the chemical structures of PGSC elastomers were hardly influenced by the MWCNT loadings, and physical adsorption was thought as the main interaction between the MWCNTs and PGSC matrixes. When the MWCNT loading was 3 wt%, MWCNTs displayed a homogenous dispersion in the matrixes, and the composite's strength and modulus respectively reached 4.4 MPa and 9.2 MPa, increasing by 62.96% and 33.33% than that of pure PGSC matrixes. The degradation rates of the composites tended to decrease with the increase of MWCNT loadings in simulated body fluid (SBF) solution. The composites presented no cytotoxicity especially when the MWCNT loadings were above 1 wt%. We expect the composites can be used as degradable bio-coatings and tissue engineering scaffolds in future.     

Synthesis of the ABCD fragment of gymnocin-B

A convergent synthesis of the ABCD fragment of gymnocin-B was accomplished. The tetracyclic ether ring system was synthesized by the construction of the BC ring system via the oxiranyl anion alkylation and ring expansion reaction, followed by the formation of the five-membered A-ring via a stereoselective radical cyclization reaction of a neopentyl-type iodide.     

The application of vinylogous iminium salt derivatives to efficient formal syntheses of the marine alkaloids lamellarin G trimethyl ether and ningalin B

Studies directed at the synthesis of lamellarin G trimethyl ether and ningalin B via vinylogous iminium salt derivatives are described. The successful strategy relies on the formation of a 2,4-disubstituted pyrrole or a 1,2,3,4-tetrasubstituted pyrrole from a vinylogous iminium salt or vinylogous iminium salt derivative. Subsequent transformations of these highly substituted pyrroles lead to efficient and regiocontrolled formal syntheses of the respective pyrrole containing natural products.     

The application of vinylogous iminium salt derivatives to an efficient synthesis of the pyrrole containing alkaloids Rigidin and Rigidin E

Studies directed on the synthesis of the pyrrole containing marine natural products Rigidin and Rigidin E via vinylogous iminium salts are described. The successful strategy relies on the formation of a 2,4-disubstituted pyrrole from a vinamidinium salt followed by acylation at the 5-position of pyrrole. Halogenation and aminocarbonylation at the 3-position of pyrrole followed by hydrolysis of the ester group at C-2 and subsequent Curtius rearrangement generates the pyrrolopyrimidine skeleton. A final deprotection step completes the synthesis of Rigidin and Rigidin E.