Gymnangiamide, a cytotoxic pentapeptide from the marine hydroid Gymnangium regae

A cytotoxic aqueous extract from the marine hydroid Gymnangium regae provided a novel linear pentapeptide, designated gymnangiamide (1). The planar structure of 1 was elucidated by interpretation of spectral data as well as chemical degradation and derivatization studies. In addition to the amino acids isoleucine and phenylserine, this peptide contained N-desmethyldolaisoleuine, O-desmethyldolaproine, and alpha-guanidino serine, three residues that have not previously been reported in a natural product. The absolute configurations of the constituent amino/guanidino acids were determined by chemical degradation and derivatization, followed by HPLC and LC-MS comparison with authentic standards. Gymnangiamide (1) was moderately cytotoxic against a number of human tumor cell lines in vitro.     

Isolation, structure determination, and synthesis of neodysiherbaine A, a new excitatory amino acid from a marine sponge

[structure: see text] A new excitatory amino acid, neodysiherbaine A (2), was isolated as a minor constituent of the aqueous extract from the marine sponge Dysidea herbacea. The structure was deduced by spectroscopic methods and established unambiguously by the total synthesis. The present synthesis, including as a key step cross-coupling of the 6/5-bicyclic core with an amino acid residue, is useful in constructing its structural analogues.     

Isolation, structure, and synthesis of dolastatin D, a cytotoxic cyclic depsipeptide from the sea gare Dolabella auricularia

Dolastatin D (1), a cytotoxic cyclic depsipeptide possessing the novel β-amino acid (2R,3R)-3-amino-2-methylbutanoic acid [(2R,3R]-3] as a component, has been isolated from the Japanese sea hare Dolabella auricularia. The absolute stereostructure of 1 was elucidated on the basis of spectroscopic analysis and chemical degradation and was further confirmed by synthesis.     

Isolation and structure of sergeolide,a potent cytotoxic quassinoid from picrolemma pseudocoffea

Sergeolide $\text{2}$, isolated from the French Guyanan Simaroubaceae, Picrolemma pseudocoffea Ducke, is a novel quassinoid possessing the normal C₂₀ basic skeleton with a butenolide function attached to the A ring. Structure $\text{2}$ was established by interpretation of the 400 MHz ¹H-NMR and the ¹³C-NMR data. It is highly cytotoxic and is active against mouse leukemia P388. The previously known isobruceine B $\text{1}$ was also isolated.     

Total synthesis of proposed structure of coibamide A,a highly N- and O-methylated cytotoxic marine cyclodepsipeptide

Total synthesis of the originally proposed structure of coibamide A, a highly N- and O-methylated cytotoxic marine cyclodepsipeptide, has been accomplished by using a [(4+1)+3+3]-peptide fragment-coupling strategy and careful examination and optimization of the multiple dense N-methylated amide-bond formations. The synthetic sample of the proposed coibamide A could not match the natural product in both ¹H and ¹³C NMR spectra, but was found to exhibit low micromolar cytotoxicity against the proliferation of three tested cancer cells.     

Scytalidamides A and B, new cytotoxic cyclic heptapeptides from a marine fungus of the genus Scytalidium

Two new cyclic heptapeptides have been isolated from the culture broth of a marine fungus, Scytalidium sp., collected from the Bahamas. The planar structures of scytalidamides A (1) and B (2) were assigned on the basis of 1D and 2D NMR spectroscopic techniques, while the absolute configuration of the amino acid residues in both molecules was determined by application of the advanced Marfey's method. The absolute stereochemistry of the uncommon 3-methylproline moiety in scytalidamide B (2) was confirmed by isolation and CD measurements, as well as application of the advanced Marfey's method. Scytalidamides A (1) and B (2) showed moderate in vitro cytotoxicity toward HCT-116 human colon adenocarcinoma with IC(50) values of 2.7 and 11.0 microM, respectively.     

Isolation and structure determination of the biologically active sphingolipids from marine sponge Haliclona species

In a continuation to our study on the marine sponge Haliclona species we have isolated three new cytotoxic components of sphingolipids (1-3). Methanolysis of the sphingolipid 1a-d in methanol produces fatty acid methyl ester. GC/MS was used to determine the length. The structure of each isolated compound has been determined on the basis of spectroscopic data and chemical evidence.     

Characterization,crystal structure and cytotoxic activity of a rare iridoid glycoside from Lonicera saccata

A new iridoid glycoside, methyl (3R,4R,4aS,7S,7aR)‐3‐hydroxy‐7‐methyl‐5‐oxooctahydrocyclopenta[c]pyran‐4‐carboxylate‐3‐O‐β‐d ‐(1′S,2′R,3′S,4′S,5′R)‐glucopyranoside, named loniceroside A, C₁₇H₂₆O₁₀, ( 1 ), was obtained from the aerial parts of Lonicera saccata. Its structure was established based on an analysis of spectroscopic data, including 1D NMR, 2D NMR and HRESIMS, and the configurations of the chiral C atoms were determined by X‐ray crystallographic analysis. The single‐crystal structure reveals that the cyclopenta[c]pyran scaffold is formed from a five‐membered ring and a chair‐like six‐membered ring connected through two bridgehead chiral C atoms. In the solid state, the glucose group of ( 1 ) plays an important role in constructing an unusual supramolecular motif. The structure analysis revealed adjacent molecules linked together through intermolecular O—H…O hydrogen bonds to generate a banded structure. Furthermore, the banded structures are linked into a three‐dimensional network by interesting hydrogen bonds. Biogenetically, compound ( 1 ) carries a glucopyranosyloxy moiety at the C‐3 position, representing a rare structural feature for naturally occurring iridoid glycosides. The growth inhibitory effects against human cervical carcinoma cells (Hela), human lung adenocarcinoma cells (A549), human acute mononuclear granulocyte leukaemia (THP‐1) and the human liver hepatocellular carcinoma cell line (HepG2) were evaluated by the MTT method.     

Isolation, synthesis and structures of cytotoxic ginsenoside derivatives

Four known ginsenosides: ginsenoside-Rb1 (1), Rb3 (2), Rd (3) and Re (4) were isolated from the methanolic extract of the traditional Chinese medicine Panax ginseng C. A. Meyer. Further enzyme reactions and chemical modifications led us to obtain ginsenoside-M1 (5) and synthesize three novel mono-esters of ginsenoside-M1, ginsenoside-DM1 (6), PM1 (7) and SM1 (8) 30 - 50% of yield via a facile and green synthetic strategy. The structures were elucidated on the basis of extensive 1D- and 2DNMR, as well as high resolution ESI-TOF mass spectroscopic analyses. The isolated and synthetic compounds were tested in an anti-tumor bioassay, and compounds 5-8 showed considerable cytotoxicity (SRB) against several human cancer cell lines (breast cancer MCF-7, skin melanoma SK-MEL-2 and human ovarian carcinoma B16), but moderate effects on lung carcinoma COR-L23. The other ginsenosides showed no effects.     

Isolation, structure determination, and synthesis of allo-RA-V and neo-RA-V, RA-series bicyclic peptides from Rubia cordifolia L

Two bicyclic hexapeptides, allo-RA-V (4) and neo-RA-V (5), and one cyclic hexapeptide, O-seco-RA-V (6), were isolated from the roots of Rubia cordifolia?L. Their gross structures were elucidated on the basis of spectroscopic analysis and X-ray crystallography of compound 5. The absolute stereochemistry of compounds 4 and 5 were established by their total syntheses, and the absolute stereochemistry of compound 6 by chemical correlation with deoxybouvardin (3). Comparison of the 3D structures of highly active RA-VII (1) with less-active compounds 4 and 5 suggests that the orientation of the Tyr-5 and/or Tyr-6 phenyl rings plays a significant role in their biological activity. The isolation of peptides 4-6, along with compound 3, and the comparison of their structures seem to indicate that peptide 6 may be the common precursor to bicyclic peptides 3-5 in the plant.     

New methods and reagents in organic synthesis. 51. A synthesis of ascidiacyclamide,a cytotoxic cyclic peptide from ascidian — determination of its absolute configuration

A first synthesis of ascidiacyclamide, a cytotoxic cyclic peptide from ascidian, has been achieved through the cyclodimerization with diphenyl phosphorazidate(DPPA), which has unambiguously determined the absolute configuration of ascidiacyclamide as $\text{1}$.     

First enantioselective synthesis of salinipostin A,a marine cyclic enol-phosphotriester isolated from Salinispora sp

Salinipostins are cyclic enol-phosphotriesters isolated from a marine-derived Salinispora sp. as antimalarial compounds. Herein, the first enantioselective synthesis of salinipostin A was achieved. Organocatalyst-mediated asymmetric cyclopropanation and regioselective cyclopropane ring opening were the key steps.     

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.     

Isolation and structure determination of lysiformine from bacteria associated with marine sponge Halichondria okadai

Marine sponge Halichondria okadai is a source of numerous toxic secondary metabolites, which are considered as products of the symbiotic species associated with the sponge. In this study, we tested 720 culture conditions and purified 48 sponge-associated microbes. The ethyl acetate extract from the liquid culture of each species was tested for cytotoxicity, hemolytic activity, and brine shrimp lethal activity. Lysiformine (1) was isolated from Lysinibacillus fusiformis and its structure was determined by HRMS and NMR.     

Biomimetic synthesis and structure elucidation of rubicordifolin, a cytotoxic natural product from Rubia cordifolia

The biomimetic synthesis and full structural elucidation of rubicordifolin, a cytotoxic natural product isolated from Rubia cordifolia, is described.     

New methods and reagents in organic synthesis. 58. : A synthesis of patellamide a, a cytotoxic cyclic peptide from a tunicate. Revision of its proposed structure

The real structure of patellamide A, a cytotoxic lipophilic cyclic peptide from a marine tunicate, has been unambiguously determined by the synthesis of both its proposed and revised structures.     

Design and synthesis of all diastereomers of cyclic pseudo-dipeptides as mimics of cyclic CXCR4 pentapeptide antagonists

The four diastereomers of 2,5-bis[(3-guanidino)propyl]-1-[3-(4-hydroxyphenyl)propionyl]-7-(2-naphthylacetyl)-1,4,7-triazacycloundec-9-en-3-one (-) and of 2,5-bis[(3-guanidino)propyl]-1-(4-hydroxyphenylacetyl)-7-(2-naphthylacetyl)-1,4,7-triazacycloundec-9-en-3-one (-) were synthesized by a divergent methodology from l- and D-glutamic acids. The 11-membered ring core was made by ring closing metathesis of linear bis(allylamines), and the guanidyl functions were introduced by a simultaneous double Mitsunobu reaction using bis(Boc)guanidine. These compounds were designed to mimic cyclic pentapeptide FC131 (c[Gly-D-Tyr-Arg-Arg-Nal]).