Kyanamide,a new Ahp-containing depsipeptide from marine cyanobacterium Caldora penicillata

Kyanamide (1), a new depsipeptide containing 3-amino-6-hydroxy-2-piperidone moiety, was isolated from the Caldora penicillata marine cyanobacterium collected in Okinawa. Its structure was determined by spectroscopic analysis and Marfey's analysis of acid hydrolysate. Kyanamide exhibited moderate cytotoxicity against HeLa S3 cells. 1 also exhibited potent protease inhibitory activity against elastase and chymotrypsin with IC₅₀ values of 0.13 nM and 1.1 μM.     

Croissamide,a proline-rich cyclic peptide with an N-prenylated tryptophan from a marine cyanobacterium Symploca sp.

Croissamide, a proline-rich cyclic peptide that contains an N-prenylated tryptophan, was isolated from a marine cyanobacterium Symploca sp. Its gross structure was determined by spectroscopic analyses, and the absolute configuration was established based on chiral HPLC analyses of acid hydrolysates.     

First synthesis of both enantiomers of pseudohygrophorone A12, an anti-fungal cyclohexenone derivative isolated from Hygrophorus abieticola

Pseudohygrophorone A¹², a highly oxygenated cyclohexenone derivative isolated from Hygrophorus abieticola, exhibits anti-fungal activity against several phytopathogenic fungi and oomycete. The first synthesis of both enantiomers of pseudohygrophorones A¹² was accomplished starting from an optically active sulfoxide. In our approach, the diastereoselective Michael?aldol cascade reaction was featured as the key step.     

Cyclic diarylheptanoids deoxycymodienol and isotedarene A from Zostera marina (Zosteraceae)

A first phytochemical investigation of apolar natural products of the seagrass Zostera marina L. (Zosteraceae) yielded cymodienol, a cyclic diarylheptanoid so far only known from the seagrass Cymodocea nodosa (Ucria) Asch. (Cymodoceaceae) and a previously undescribed diaryheptanoid, isotedearene A, which is closely related to tedarene A, a natural product previously described from the neotropic sponge Tedania ignis (Duchassaing & Michelotti, 1864) (Tedaniidae). Structures were established by mass spectrometry and extensive 1D and 2D NMR experiments.     

An enantioselective synthesis of a MEM-protected aetheramide A derivative

Aetheramides A and B are very potent anti-HIV agents. An enantioselective synthesis of a MEM-protected aetheramide A derivative is described. The synthesis was accomplished in a convergent and stereoselective manner. The key reactions involved asymmetric dihydroxylation, asymmetric allylation, asymmetric syn-aldol reactions, and asymmetric hydrogenation.     

Total synthesis of ulongamide A, a cyclic depsipeptide isolated from marine cyanobacteria Lyngbya sp.

A total synthesis of ulongamide A (1), a cytotoxic natural cyclic depsipeptide, was achieved by a convergent route involving coupling of the fragments 7 and 8 to the pentapeptide 24, and subsequent cyclization thereof after prior removal of the t-Boc protecting groups.     

First asymmetric enantioselective total synthesis of phenanthridine alkaloid, (S)-(+)-asiaticumine and its enantiomer

In this study, the first asymmetric enantioselective total syntheses of (+)-asiaticumine A (2) and its enantiomer were accomplished through a seven-step sequence using the bond formation between the C4a and N5 positions of the phenanthridine framework based on the microwave-assisted electrocyclization of cyclohexenylbenzaldoxime methyl ether as an aza 6π-hexatriene system followed by the Sharpless asymmetric dihydroxylation as the key step. In addition, the absolute configuration of natural (+)-2 was determined to be S by Mosher’s method.     

Poecillastrin E,F, and G,cytotoxic chondropsin-type macrolides from a marine sponge Poecillastra sp.

Poecillastrin E (1), F (2), and G (3) were isolated from a marine sponge Poecillastra sp. as the cytotoxic constituents. Their planar structures were determined by analyzing the MS and NMR spectra. They are closely related to the known poecillastrin C (4). The absolute configuration of the β-hydroxyaspartic acid (OHAsp) residue was determined to be D-threo by Marfey's analysis of the hydrolysate. The mode of lactone ring formation of OHAsp residue in 1–3 was determined by selective reduction of the ester linkage followed by acid hydrolysis.     

A practical asymmetric synthesis of ortho-substituted 4-pyrazolyl-2-ethylamines

A reliable three-step synthesis of ortho-substituted 4-pyrazolyl-2-ethylamines starting from a pyrazole methyl ketone and N-tert-butanesulfinylamine is described. Strongly dehydrating conditions were required to form the N-tert-butanesulfinyl ketimines, but these intermediates were stable to aqueous work-up and chromatography. Reduction of N-tert-butanesulfinyl ketimines with L-selectride®, or Super-hydride®, in THF afforded excellent yields and diastereoselectivities of the sulfinamides, which were converted into chiral amines with methanolic HCl. The 4-pyrazolyl-2-ethylamines from these investigations are attractive building blocks for medicinal chemists, as they exhibit low molecular weight, and low calculated octanol-water partition coefficient (c Log P values), while disrupting planarity with three-dimensional character. For example, the amine products were utilized in structure-activity studies of the human transient receptor potential vanilloid 1 (TRPV1/VR1).     

Heterogeneous synthesis of glycerol carbonate from glycerol and dimethyl carbonate catalyzed by LiCl/CaO

In this article, a CaO-based catalyst was prepared by impregnating chloride salts on CaO to develop a highly efficient heterogeneous catalyst for the synthesis of glycerol carbonate (GC) from glycerol and dimethyl carbonate. LiCl/CaO exhibited a high catalytic activity under moderate reaction conditions. The effects of the LiCl loadings, the amount of catalyst and the calcination temperature on the catalytic activity were investigated. The highest yield of 94.19% glycerol carbonate was obtained at 65 °C on CaO loaded with 10% LiCl after 1 h, and the catalyst had high stability in reusing work. Scanning electron microscopy (SEM), X-ray diffraction (XRD), BET, CO₂-TPD, XPS and thermalgravity (TG) were used to characterize the prepared catalyst. It was found that the high catalytic activity of CaO after modification with LiCl is associated with the structural aspects and the amount of basicity of the catalyst. The Li₂O₂ species, which is a strong basic site that is formed by the substitution of the Ca²⁺ in CaO lattice by Li⁺, has great activity for transesterification.     

First enantioselective synthesis of exiguamide,a nitrogen-containing spirocyclic sesquiterpene isolated from the marine sponge Geodia exigua

(+)-Exiguamide is a nitrogen-containing spirocyclic sesquiterpene isolated from the marine sponge Geodia exigua. This study aims to report the first synthesis of both enantiomers of exiguamide, featuring the stereoselective intramolecular cyclopropanation and stereoselective homoconjugate addition of azide to cyclopropyl ketone as the key steps.     

Belamide A, a new antimitotic tetrapeptide from a Panamanian marine cyanobacterium

The isolation and structure elucidation of belamide A from the marine cyanobacterium Symploca sp. is described. Belamide A is a highly methylated linear tetrapeptide with structural analogy to the important linear peptides dolastatins 10 and 15. Disruption of the microtubule network in A-10 cells was observed at 20 μM and displayed classic tubulin destabilizing antimitotic characteristics. The moderate cytotoxicity of belamide A (IC₅₀ 0.74 μM vs HCT-116 colon cancer line) provides new insights into structure-activity relationships for this drug class.     

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.     

Synthesis of enantiomerically pure 2-(N-aryl,N-alkyl-aminomethyl)aziridines: a new class of ligands for highly enantioselective asymmetric synthesis

A simple and effective synthesis of enantiomerically pure 2-(N-aryl-, N-alkyl-aminomethyl)aziridines from (2S)-N-tritylaziridine-2-carboxylic acid methyl ester has been developed. Treating of this key ester with several primary and secondary amines in the presence of AlMe₃ provided the corresponding chiral N-trityl-2-carboxamides, and their reduction performed with different reagents resulted in the formation of the expected 2-(aminomethyl)aziridines. The choice of reaction conditions allows to either keep or leave the trityl substituent in the product. Such 2-(aminoalkyl)aziridines have shown very high catalytic efficiency in the asymmetric arylation of aldehydes and in other testing asymmetric reactions. On the other hand, homochiral N-trityl-2-carboxamides are interesting building blocks for the synthesis of various biologically active compounds.     

Solid phase total synthesis of callipeltin E isolated from marine sponge Latrunculia sp.

Solid phase total synthesis of callipeltin E (1), truncated linear peptide isolated from marine sponge, Latrunculia sp. was achieved. Our strategy based on traditional Fmoc-SPPS was in common use TFA-treatment final deprotection to reach callipeltin E (1) contained acid-sensitive βMeOTyr.     

A new isobenzofuranone derivative from a marine Streptomyces sp.

One new isobenzofuranone derivative,1,4-dimethoxy-3-(3R*-hydroxy-3R*-methyl-1-tetralone)-1(3H)-isobenzofuran(1),was isolated from the broth of marine Streptomyces sp.M268.The structure was elucidated by spectroscopy characteristics as well as comparison with the literature.Compound 1 exhibited cytotoxicities against human cancer cell,HL-60,A549,and BEL-7402.     

Nitricquinomycins A-C,uncommon naphthopyrrolediones from the Streptomyces sp. ZS-A45

Nitricquinomycins A-C (1～3), three uncommon naphthopyrrolediones, together with one new compound (4), were isolated from the modified rice solid fermentation of the marine-derived Streptomyces sp. ZS-A45, an actinobacterium isolated from the marine sediments collected from Zhoushan island. Their structures were elucidated on the basis of MS, NMR spectroscopic and quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compounds 3 and 4 exhibited significant cytotoxicity against A2780 cell lines with IC₅₀ values of 4.77 and 2.92 μM, respectively; on the other hand, compound 3 exhibited moderate antibacterial activities against Escherichia coli, Staphylococcus aureus and Candida albicans with MIC values of 20.0 40.0 and 40.0 μM, respectively.     

First total synthesis of versicotide D and analogs

The first total synthesis of cyclotetrapeptide versicotide D has been achieved in 21% overall yield using solid phase peptide synthesis and solution cyclization. In addition, in the search for candidates of antimalarial new drugs, one cyclic tetrapeptide analog which differs in the sequence, and four cyclic pentapeptide containing N-methyl amino acids, were prepared. The obtained compounds were evaluated against P. falciparum 3D7. Versicotide D showed low micromolar antiplasmodial activity.     

Cereusitin A,a cyclic tetrapeptide from a Bacillus cereus strain isolated from the soft coral Antillogorgia (syn. Pseudopterogorgia) elisabethae

Two new compounds, cereusitin A (1), the tetrapeptide cyclo-(L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-leucyl-trans-4-hydroxy-L-proline and 4-(R)-hydroxysattabacin (2), along with the methyl, isopropyl, and propyl esters of p-hydroxybenzoic acid (3–5) were isolated from the organic extracts of the culture of the B. cereus RKHC-09 strain in two culture media (MOLP and B1), recovered from the sea fan Antillogorgia elisabethae (syn. Pseudopterogorgia elisabethae). Cereusitin A (1) showed mild antifungal activity against Colletotrichum gloeosporoides C26 (yam pathogen) but was inactive against Fusarium oxysporum f.sp. dianthi (carnation pathogen). The methyl and propyl esters of p-hydroxybenzoic acid (4 and 5) showed antimicrobial activity against S. aureus ATCC 33591 and S. cerevisiae, with an MIC of 2 μM.     

Spongiains A-C: Three new spongian diterpenes with ring A rearrangement from the marine sponge Spongia sp.

Spongiains A-C (1–3), the first examples of spongian diterpenes bearing a pentacyclic skeleton composed of a fused 5/5/6/6/5 ring system through ring A rearrangement, together with four new spongian diterpenes, spongiains D-G (4–7), were isolated from the marine sponge Spongia sp.. The structures with absolute configurations of these compounds were elucidated by the methods of NMR, X-ray diffraction and quantum chemical approaches. The hypothetical biogenetic pathways as well as cytotoxic activities of 1–7 were also discussed.