Synthesis ofα-triazolylα-amino acid derivatives

Summary We report the synthesis of-triazolyl-amino esters by 1,3 dipolar cycloaddition of acetylenic compounds and-azido-amino esters.     

Amphiphilic molecular gels from ω-aminoalkylated l-glutamic acid derivatives with unique chiroptical properties

Self-assembling amphiphiles with unique chiroptical properties were derived from l-glutamic acid through ω-aminoalkylation and double long-chain alkylation. These amphiphiles can disperse in various solvents ranging from water to n-hexane. TEM and SEM observations indicate that the improvement in dispersity is induced by the formation of tubular and/or fibrillar aggregates with nanosized diameters, which makes these amphiphiles similar to aqueous lipid membrane systems. Spectroscopic observations, such as UV–visible and CD spectroscopies indicate that the aggregates are constructed on the basis of S- and R-chirally ordered structures through interamide interactions in water and organic media, respectively, and that these chiroptical properties can be controlled thermotropically and lyotropically. It is also reported that the chiral assemblies provide specific binding sites for achiral molecules and then induce chirality for the bonded molecules. Further, the applicability of the amphiphiles to template polymerization is discussed.     

Bicyclic α,ω-dicarboxylic acid derivatives from a colonial tunicate of the family Polyclinidae

In the course of our search for bioactive metabolites from a colonial tunicate of the family Polyclinidae, six new (1–6) cyclic fatty acid derivatives were isolated. Their planar structures were established on the basis of NMR and MS spectroscopic analyses. The relative configuration was determined by NOESY experiment. Compounds 1–6 represent a fused bicyclic skeleton possibly derived from α,ω-dicarboxylic acids such as eicosanedioic acid or docosanedioic acid via a Diels–Alder type of cyclization. Compounds 1–4 and 6 showed mild cytotoxicity against a panel of five human solid tumor cell lines.     

Synthesis of chimera oligopeptide including furanoid β-sugar amino acid derivatives with free OHs: mild but successful removal of the 1,2-O-isopropylidene from the building block

Complementary to hydrophobic five membered ring β-amino acids (e.g. ACPC), β-sugar amino acids (β-SAAs) have found increasing application as hydrophilic building blocks of foldamers and α/β chimeric peptides. Fmoc-protected β-SAAs [e.g. Fmoc-RibAFU(ip)-OH] are indeed useful Lego elements, ready to use for SPPS. The removal of 1,2-OH isopropylidene protecting group increasing the hydrophilicity of such SAA is presented here. We first used N₃-RibAFU(ip)-OH model compound to optimize mild deprotection conditions. The formation of the 1,2-OH free product N₃-RibAFU-OH and its methyl glycoside methyl ester, N₃-RibAFU(Me)-OMe were monitored by RP-HPLC and found that either 50% TFA or 8 eqv. Amberlite IR-120 H⁺ resin in MeOH are optimal reagents for the effective deprotection. These conditions were then successfully applied for the synthesis of chimeric oligopeptide: -GG-X-GG- [X=RibAFU(ip)]. We found the established conditions to be effective and—at the same time—sufficiently mild to remove 1,2-O-isopropylidene protection and thus, it is proposed to be used in the synthesis of oligo- and polypeptides of complex sequence combination.

     

α-Methylene-γ-aminobutyric acid from Mycena pura

α-Methylene-γ-aminobutyric acid was isolated and characterized from fruit bodies of Mycena pura. It was the decarboxylation product of l-γ-methyleneglutamic acid by l-glutamic acid decarboxylase.     

α-Lipoic acid dependent regeneration of ascorbic acid from dehydroascorbic acid in rat liver mitochondria

Rat liver mitochondria were examined for their ability to reduce dehydroascorbic acid to ascorbic acid in an -lipoic acid dependent or independent manner. The a-lipoic acid dependent reduction was stimulated by factors that increased the NADH dependent reduction of -lipoic acid to dihydrolipoic acid in coupled reactions. Optimal conditions for dehydroascorbic acid reduction to ascorbic acid were achieved in the presence of pyruvate, -lipoic acid, and ATP. Electron transport inhibitors, rotenone and antimycin A, further enhanced the dehydroascorbic acid reduction. The reactions were strongly inhibited by 1 mM iodoacetamide or sodium arsenite. Mitoplasts were qualitatively similar to intact mitochondria in dehydroascorbate reduction activity. Pyruvate dehydrogenase and -ketoglutarate dehydrogenase reduced dehydroascorbic acid to ascorbic acid in an -lipoic acid, coenzyme A, and pyruvate or -ketoglutarate dependent fashion. Dehydroascorbic acid was also catalytically reduced to ascorbic acid by purified lipoamide dehydrogenase in an -lipoic acid (K _0.5=1.4±0.8 mM) and lipoamide (K _0.5=0.9±0.3 mM) dependent manner.     

α-Santalol derivatives from Santalum album and their cytotoxic activities

A bioassay-guided fractionation of the heartwood of Santalum album led to the isolation of seven α-santalol derivatives including (9S,10E)-9-hydroxy-α-santalal, (10R,11S)-10,11-dihydroxy-α-santalol, (9E)-11,13-dihydroxy-α-santalol, and (10E)-12-hydroxy-α-santalic acid. Their structures were determined on the basis of results of spectroscopic analysis, including two-dimensional (2D) NMR spectroscopic data. The isolated compounds and derivatives were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells and TIG-3 normal human diploid fibroblasts. Of these (9S,10E)-9-hydroxy-α-santalal, exhibited tumor-selective cytotoxicity. The apoptosis induction properties of sesquiterpenes with cytotoxic potency in HL-60 cells are also described.     

Identification of mollic acid α-L-arabinoside,a 1α-hydroxycycloartenoid from Combretum molle leaves

A further novel 1α-hydroxycycloartane glycoside, mollic acid α-L-arabinoside, has been identified in the leaves of Combretum molle.     

Formation ofα,ω-dodecanedioic acid andα,ω-tridecanedioic acid from different substrates by immobilized cells of a mutant ofCandida tropicalis

Summary The metabolic formation of either,-dodecanedioic acid or,-tridecanedioic acid from the individual n-alkane, n-alcohol, n-monoacid and,-diol with corresponding carbon chain length using K-carrageenan entrapped mutants S76 ofCandida tropicalis was studied. The immobilized cells of S76 could also directly produce-hydroxy acid and,-dioic acid from,-diol. With n-alcohol and n-monoacid as substrate, the amount of-hydroxy acid and,-dioic acid produced was also a function of the incubation time.The results demonstrated that in the immobilized cells of S76 the formation of,-dioic acid from n-alcohol can also run both via n-monoacid and via,-diol as well as in the normal cells of S76.     

Sulphate esters of hydroxycinnamic acid—sugar derivatives from Adiantum capillus-veneris

Two new and two known sulphate esters of hydroxycinnamic acid—sugar derivatives have been isolated from the fronds of the fern Adiantum capillus-veneris. The new compounds have been shown to be 1-p-coumarylglucose 2-sulphate and 1-caffeylgalactose 6-sulphate by chemical and spectroscopic methods.     

α-pyrone derivatives from endophytic fungus Diaporthe sp. RJ-41

A new α-pyrone derivative 1 and six known α-pyrone derivatives 2–7, along with known compounds 8–10 were isolated from the fermentation products of the endophytic fungus Diaporthe sp. RJ-41. Among them, nine compounds (1–9) were reported for the first time from the genus Diaporthe. This work expanded the knowledge of the chemical diversity of the genus Diaporthe, and the chemotaxonomic significance of the isolates was also discussed.     

α-Pyrone derivatives with cytotoxic activities,from the endophytic fungus Phoma sp. YN02-P-3

Four new α-pyrone derivatives phomones C-F (1?4) together with four known compounds (5?8) were isolated from the endophytic fungus Phoma sp. YN02-P-3. Compound 1 is the first example of 6-α,β-unsaturated ester-2-pyrone dimers via intermolecular symmetrical [2 + 2] cycloaddition. The chemical structures of these compounds were determined from spectroscopic data (1D/2D NMR, MS and IR). The acetylated product (9) of 1 along with compounds 1–8 were then tested for their cytotoxicity against HL-60, PC-3 and HCT-116 cell lines. Compounds 2, 3, 5 and 9 with acetyl groups showed significant inhibitory activities against the three cell lines with IC₅₀ values in the range 0.52–9.85 μM. while compounds 1, 4 and 6–8 that possess no acetyl group showed no inhibitory activity (IC₅₀ > 50 μM), indicating that the acetyl group at 10- or 12- are essential for their cytotoxic activities. The structure-activity relationships of these phomones were also reported.     

8R-Lipoxygenase-catalyzed synthesis of a prominent cis-epoxyalcohol from dihomo-γ-linolenic acid: a distinctive transformation compared with S-lipoxygenases

Conversion of fatty acid hydroperoxides to epoxyalcohols is a well known secondary reaction of lipoxygenases, described for S-specific lipoxygenases forming epoxyalcohols with a trans-epoxide configuration. Here we report on R-specific lipoxygenase synthesis of a cis-epoxyalcohol. Although arachidonic and dihomo-γ-linolenic acids are metabolized by extracts of the Caribbean coral Plexaura homomalla via 8R-lipoxygenase and allene oxide synthase activities, 20:3ω6 forms an additional prominent product, identified using UV, GC-MS, and NMR in comparison to synthetic standards as 8R,9S-cis-epoxy-10S-erythro-hydroxy-eicosa-11Z,14Z-dienoic acid. Both oxygens of (18)O-labeled 8R-hydroperoxide are retained in the product, indicating a hydroperoxide isomerase activity. Recombinant allene oxide synthase formed only allene epoxide from 8R-hydroperoxy-20:3ω6, whereas two different 8R-lipoxygenases selectively produced the epoxyalcohol.A biosynthetic scheme is proposed in which a partial rotation of the reacting intermediate is required to give the observed erythro epoxyalcohol product. This characteristic and the synthesis of cis-epoxy epoxyalcohol may be a feature of R-specific lipoxygenases.     

4′-Alkoxy derivatives of abscisic acid: a promising new probe for mechanisms of abscisic acid perceptions

The preparation of new compounds for exploring the molecular andbiochemical mechanisms of abscisic acid signal perception is described. The4-carbonyl group of abscisic acid was replaced with either benzyloxy orn-octyloxy groups. Both modified products possessedABA-like activity in bioassays using barley aleurone protoplasts. The benzyloxyderivative was active in dehydrin induction tests, but not in inhibition of-amylase induction tests. The difference in the activity of this chemical inthe two assay systems suggests that the perception system for the inhibition ofamylase induction systems differs from that of dehydrin induction.     

Identification and characterization of two bile acid coenzyme A transferases from Clostridium scindens, a bile acid 7α-dehydroxylating intestinal bacterium

The human bile acid pool composition is composed of both primary bile acids (cholic acid and chenodeoxycholic acid) and secondary bile acids (deoxycholic acid and lithocholic acid). Secondary bile acids are formed by the 7α-dehydroxylation of primary bile acids carried out by intestinal anaerobic bacteria. We have previously described a multistep biochemical pathway in Clostridium scindens that is responsible for bile acid 7α-dehydroxylation. We have identified a large (12 kb) bile acid inducible (bai) operon in this bacterium that encodes eight genes involved in bile acid 7α-dehydroxylation. However, the function of the baiF gene product in this operon has not been elucidated. In the current study, we cloned and expressed the baiF gene in E. coli and discovered it has bile acid CoA transferase activity. In addition, we discovered a second bai operon encoding three genes. The baiK gene in this operon was expressed in E. coli and found to encode a second bile acid CoA transferase. Both bile acid CoA transferases were determined to be members of the type III family by amino acid sequence comparisons. Both bile acid CoA transferases had broad substrate specificity, except the baiK gene product, which failed to use lithocholyl-CoA as a CoA donor. Primary bile acids are ligated to CoA via an ATP-dependent mechanism during the initial steps of 7α-dehydroxylation. The bile acid CoA transferases conserve the thioester bond energy, saving the cell ATP molecules during bile acid 7α-dehydroxylation. ATP-dependent CoA ligation is likely quickly supplanted by ATP-independent CoA transfer.     

Novel γ-lactone derivatives from Trigonostemon heterophyllus with their potential antiproliferative activities

Two novel γ-lactone derivatives, trigoheterophines A (1) and B (2), together with four known furan derivatives (3–6), were isolated from the stems and leaves of Trigonostemon heterophyllus. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparing with the data reported in literature. Among them, trigoheterophines A (1) and B (2) represent an unusual type of γ-lactone derivatives, possessing 21 carbon atoms on the carbon skeleton, and known compouds (3–6) are rare furan derivatives in the plant kingdom with diverse long-chain hydrocarbyl groups as substituents at C-4. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1–6 showed significant antiproliferative effects against various human cancer cell lines with IC₅₀ values ranging from 0.28 to 12.06 μM. These findings suggest that the discoveries of these novel γ-lactone derivatives and furan derivatives with significant antiproliferative activities isolated from T. heterophyllus could be of great importance to the development of new anticancer agents.