Showing papers in "Helvetica Chimica Acta in 2013"

Stoichiometric Reactions of Enamines Derived from Diphenylprolinol Silyl Ethers with Nitro Olefins and Lessons for the Corresponding Organocatalytic Conversions – a Survey

Abstract: The stoichiometric reactions of enamines prepared from aldehydes and diphenyl-prolinol silyl ethers (intermediates of numerous organocatalytic processes) with nitro olefins have been investigated. As reported in the last century for simple achiral and chiral enamines, the products are cyclobutanes (4 with monosubstituted nitro-ethenes), dihydro-oxazine N-oxide derivatives (5 with disubstituted nitro-ethenes), and nitro enamines derived from γ-nitro aldehydes (6, often formed after longer reaction times). The same types of products were shown to be formed, when the reactions were carried out with peptides H-Pro-Pro-Xaa-OMe that lack an acidic H-atom. Functionalized components such as alkoxy enamines, nitro-acrylates, acetamido-nitro-ethylene, or hydroxylated nitro olefins also form products carrying the diphenyl-prolinol silyl ether as a substituent. All of these products must be considered intermediates in the corresponding catalytic reactions; the investigation of their chemical properties provided useful hints about the rates, the conditions, the catalyst resting states or irreversible traps, and/or the limitations of the corresponding organocatalytic processes. High-level DFT and MP2 computations of the structures of alkoxy enamines and thermodynamic data of a cyclobutane dissociation are also described. Some results obtained with the stoichiometrically prepared intermediates are not compatible with previous mechanistic proposals and assumptions.

Nigerasterols A and B, Antiproliferative Sterols from the Mangrove-Derived Endophytic Fungus Aspergillus niger MA-132

Abstract: Two new 6,8(14),22-hexadehydro-5,9-epidioxy-3,15-dihydroxy sterols, nigerasterols A and B (1 and 2, resp.), together with two known cyclopentapeptides, malformins A1 and C (3 and 4, resp.), were identified in the culture extract of Aspergillus niger MA-132, an endophytic fungus isolated from a fresh healthy sample of the mangrove plant Avicennia marina. The structures and relative configurations of these compounds were established on the basis of extensive spectroscopic analyses. The absolute configuration of compound 1 was determined by application of a modified version of Mosher's method. Nigerasterols A and B (1 and 2, resp.) represent the first 5,9-epidioxy-sterol compounds of marine origin, and they displayed potent activity against tumor cell lines HL60 and A549 in a preliminary bioassay.

New Cytotoxic Triterpenoids from the Aerial Parts of Euphorbia sieboldiana

Abstract: Phytochemical investigation of the EtOH extract of Euphorbia sieboldiana led to the isolation of four new oleanane-type triterpenoids, (1β,2α,3β,19β)-1,2,3,19-tetrahydroxyolean-12-en-28-oic acid, (1β,3β,19β)-1,3,19-trihydroxyolean-12-en-28-oic acid, (1β,2α,3β,16β,19β)-1,2,3,16,19-pentahydroxyolean-12-en-28-oic acid, and (1β,2α,3β,19β,23)-1,2,3,19,23-pentahydroxyolean-12-en-28-oic acid, along with 16 known compounds. Their structures were established by extensive 1D- and 2D-NMR, as well as other spectral analyses. Biological evaluation of the four new triterpenoids revealed potent cytotoxic activities against HeLa and Hep-G2 cells.

Doped Nano-Sized Copper(I) Oxide (Cu2O) on MelamineFormaldehyde Resin: a Highly Efficient Heterogeneous Nano Catalyst for ‘Click’ Synthesis of Some Novel 1H-1,2,3-Triazole Derivatives Having Antibacterial Activity

Abstract: A facile and simple protocol for the 1,3-dipolar cycloaddition of organic azides with terminal alkynes catalyzed by doped nano-sized Cu2O on melamineformaldehyde resin (nano-Cu2OMFR) as a new and convenient heterogeneous catalyst is described. In this method, ‘click’ cycloaddition of various structurally diverse β-azido alcohols and alkynes in the presence of nano-Cu2OMFR in H2O/THF 1 : 2 furnished the corresponding 1,4-disubstituted 1H-1,2,3-triazole adducts 1a–1o in good to excellent yields at room temperature (Scheme and Table 3). The nano-Cu2OMFR was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), inductively coupled plasma (ICP) analysis, and FT-IR. The nano-Cu2OMFR could be easily recovered and recycled from the reaction mixture and reused for many consecutive trials without significant decrease in activity (Table 4). The in vitro antibacterial activities of all synthesized compounds were tested on several Gram-positive and/or Gram-negative bacteria (Table 5). The results demonstrate the promising antibacterial activity for some of the synthesized compounds.

Molecular Chirality in Chemistry and Biology: Historical Milestones

Abstract: Beginning early in the 19th century, developments in crystallography, optics, and chemistry in France set the stage for the discovery of molecular chirality by Louis Pasteur in 1848. He found that the crystallization of the sodium ammonium salt of ‘paratartaric acid’, a mysterious ‘isomer’ of natural (+)-tartaric acid (TA), produced two different crystal types that were non-superimposable mirror-image forms of each other. He separated the two types and found their optical rotations in solution opposite in direction and equal in absolute magnitude. This led him to conclude that paratartaric acid is a combination of two mirror-image molecule types of TA that are ‘dissymmetric’, an existing term he adapted to the connotation of today's ‘chiral’. In 1857, he found that the two enantiomers of TA were metabolized by a microorganism at drastically different rates, and thereby discovered biological enantioselectivity. In 1886, Italian chemist Arnaldo Piutti discovered D-asparagine and found that it tasted intensely sweet, in contrast to the known L-asparagine which had no taste. This was the discovery of stereoselectivity at biological receptors. As a result of advances in stereoselective synthesis and enantioselective chromatography during the last decades of the 20th century, in the 1990s the importance of molecular chirality in drug action and disposition began to receive serious attention from drug-regulatory authorities and the pharmaceutical industry, the overall result of which has been the near-complete disappearance of racemic drugs as newly introduced pharmaceuticals.

Organic Stereochemistry. Part 3

Abstract: This review continues a general presentation of the principles of stereochemistry with special reference to medicinal compounds. Here, we discuss further stereogenic elements other than the stereogenic centers presented in Part 2. These are the axis of chirality, the plane of chirality, helicity, and (E,Z)-diastereoisomerism (stereoisomerism about double bonds). Some of these elements of stereoisomerism are not always well understood, and they raise specific convention issues. Isomerization reactions will also be discussed. As far as possible, the examples we present have biochemical and mainly medicinal relevance; a systematic overview concerning biosystems will be presented in Parts 5–8.

Synthesis of Monospiro‐2‐amino‐4H‐pyran Derivatives Catalyzed by Propane‐1‐sulfonic Acid‐Modified Magnetic Hydroxyapatite Nanoparticles

Abstract: Various monospiro-2-amino-4H-pyran derivatives have been synthesized in high yields (via three-component coupling of ninhydrin or different isatins with malononitrile and 1,3-dicarbonyl compounds) in the presence of catalytic amount of propane-1-sulfonic acid-modified magnetic hydroxyapatite nanoparticles in H2O. Due to easy magnetic removal of nanocatalyst and applying of H2O as solvent, this protocol enhanced product purity, and promised economic as well as environmental benefits, exemplifying a waste-free chemistry. More importantly, the catalyst could be easily recycled for more than five times without loss of activity.

Triazoles and other N-Containing metabolites from the marine-derived endophytic fungus penicillium chrysogenum EN-118

Abstract: Two new triazoles, chrysotriazoles A and B (1 and 2, resp.), along with two known quinazolinones, 3 and 4, two known 2-(4-hydroxyphenyl)acetamides, 5 and 6, and two known N-(4-hydroxystyryl)formamides, 7 and 8, were isolated and identified from the culture extract of Penicillium chrysogenum EN-118, an endophytic fungus obtained from the marine brown alga Sargassum pallidium. The structures of the isolated compounds were elucidated by NMR-spectroscopic analysis, and that of compound 1 was confirmed by X-ray crystallographic analysis of its p-bromobenzoate derivative. Compounds 4, 5, and 7 showed moderate cytotoxicities against Du145, A-549, and HeLa cell lines.

Homoisoflavonoids from Ophiopogon japonicus

Abstract: Phytochemical study on the root tubers of Ophiopogon japonicus resulted in the isolation and identification of 13 homoisoflavonoids, including three new compounds, 8-formyl-7-hydroxy-5,4′-dimethoxy-6-methylhomoisoflavone (1), 6-formylisoophiopogonone B (2), and 8-formylophiopogonanone B (4), and the ten known homoisoflavonoids 3, and 5–13. The absolute configurations of 8-formylophiopogonanone B (4) and 8-formyl-7-hydroxy-5,4′-dimethoxy-6-methylhomoisoflavanone (5) were confirmed by time-dependent density-functional-theory (TD DFT) calculations of their theoretical electronic circular dichroism (ECD) spectra. The structure of the formerly reported ‘6-aldehydoisoophiopogonone B’ was revised to 8-formylophiopogonone B (3). All compounds were evaluated for their cytotoxic activities against the human-lung-tumor A549 cell line, and compounds 3, 9, 10, and 13 exhibited promising antiproliferative activities with IC50 values of 10.01, 6.40, 0.84, and 1.66 μM, respectively.

Lanostane Triterpenes from Ceriporia lacerate HS‐ZJUT‐C13A, a Fungal Endophyte of Huperzia serrata

Abstract: Two new lanostane triterpenes, 3β-acetoxy-15α-hydroxylanosta-8,24-dien-21-oic acid (1) and 3β-acetoxylanosta-7,9(11),24-trien-21-oic acid (2), along with the four known analogs, 3–6, were isolated from the culture broth of Ceriporia lacerate HS-ZJUT-C13A, a fungal endophyte residing in the stems of the traditional Chinese herb Huperzia serrata. The structures of the new compounds 1 and 2 were established by spectroscopic methods, including UV, IR, HR-ESI-MS, and extensive 1D- and 2D-NMR techniques. To the best of our knowledge, this is the first report on triterpene metabolites from the genus Ceriporia.

Iridoids from the Roots of Valeriana jatamansi

Abstract: Three new iridoids, jatamanins N–P (1–3), along with the seven known iridiods 4–10, were isolated from the roots of Valeriana jatamansi. Compound 1 is an unusual iridoid bearing two epoxy bridges between C(3) and C(6) and between C(1) and C(10), forming a unique cage-like rigid skeleton. The structures of the new compounds were assigned on the basis of spectroscopic methods.

Sesterterpenes and 2H-Pyran-2-ones (=alpha-Pyrones) from the Mangrove-Derived Endophytic Fungus Fusarium proliferatum MA-84

Abstract: Two new tricyclic sesterterpenes, fusaprolifins A and B (1 and 2), and three new 2H-pyran-2-one derivatives, prolipyrones A C (35), were isolated and characterized from Fusarium proliferatum MA-84, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Bruguiera sexangula. In addition, two known sesterterpenes, terpestacin (6) and fusaproliferin (7), and one known 2H-pyran-2-one derivative, gibepyrone D (8), were also identified. The structures of these compounds were elucidated by detailed spectroscopic analyses. Fusaprolifin A (1) showed moderate activity against brine shrimp (Artemia salina), with a lethality rate of 49.5% at 100g/ml, while fusaprolifin B (2) showed weak activity.

Two New Rosane‐Type Diterpenoids from Euphorbia ebracteolata Hayata

Abstract: Two new diterpeniods, euphebracteolatins A and B (1 and 2, resp.) were isolated from Euphorbia ebracteolata Hayata, along with two known ones (3R)-ent-rosa-1(10),15-dien-3α-ol (3) and yuexiandajisu D (4). The structures were established by extensive spectroscopic analyses and comparison with literature data.

One‐Pot Synthesis of Sulfonamides and Sulfonyl Azides from Thiols using Chloramine‐T

Abstract: A convenient synthesis of sulfonamides and sulfonyl azides from thiols is described. In situ preparation of sulfonyl chlorides from thiols was accomplished by oxidation with chloramine-T (=N-chlorotosylamide=N-chloro-4-methylbenzenesulfonamide), tetrabutylammonium chloride (Bu4NCl), and H2O. The sulfonyl chlorides were then further allowed to react with excess amine or NaN3 in the same pot.

Organic stereochemistry. Part 5 : Stereoselectivity in molecular and clinical pharmacology

Abstract: This review continues a general presentation of the principles of stereochemistry with special reference to the medicinal sciences. Here, we discuss and illustrate molecular and clinical phenomena of stereoselectivity in pharmacological effects, namely activity differences between stereoisomers, principally enantiomers. The review begins with didactic models of chiral recognition, with a main focus on the early model of Easson and Stedman. There follows a Molecular Modeling (MM) and Molecular Dynamics (MD) depiction of the differential interaction of the enantiomers of hyoscyamine with cholinergic muscarinic receptors. The next section is devoted to various rationalizations in stereoselective pharmacological activity, e.g., the influence of optical purity on enantioselectivity, Pfeiffer's rule, and eudismic analysis. The review ends with selected examples taken from various fields of preclinical and clinical pharmacology, of differences between stereoisomers in terms of drug absorption, distribution, and excretion. The influence of conformational factor in molecular pharmacology will be discussed in Part 6, while stereoselective aspects of xenobiotic metabolism will be reviewed in Parts 7 and 8.

Triterpenoids from the Roots of Camellia oleifera C.Abel and Their Cytotoxic Activities

Abstract: Three new triterpenoids, 21β,22α-diangeloyloxy-3β,15α,16α,28-tetrahydroxyolean-12-en-23-al (1), 21β-angeloyloxy-3β,15α,16α,28-tetrahydroxy-22α-(2-methylbutanoyloxy)olean-12-en-23-al (2), and 21β-angeloyloxy-3β,16α,28-trihydroxy-22α-(2-methylbutanoyloxy)olean-12-en-23-al (3), along with six known triterpenoids, were isolated from the roots of Camellia oleifera C.Abel. The structures of compounds 1–3 were elucidated on the basis of spectroscopic analyses. Moreover, all compounds isolated were evaluated for their cytotoxic activities by MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay.

A New Taraxastane-Type Triterpene from Vitex trifolia var. simplicifolia

Abstract: 3-Oxotaraxer-14-en-30-al (1), a new taraxastane-type triterpene, together with 14 known compounds, taraxerone (2), 3-epiursolic acid (3), 2α,3β-dihydroxyurs-12-en-28-oic acid (4), lupeol (5), betulinic acid (6), casticin (7), artemetin (8), luteolin (9), 4-hydroxybenzoic acid (10), docosanoic acid (11), tetracosanoic acid (12), cerotic acid (13), β-sitosterol (14), and β-daucosterol (15), was isolated from the leaves and twigs of Vitex trifolia var. simplicifolia . Compounds 2–6 were found for the first time in this plant. Their structures were established by spectroscopic analysis, including 2D-NMR techniques. Cytotoxic activities of compounds 3, and 5–10 were tested on the three cancer cell lines, PANC-1, K562, and BxPC-3. Results revealed that 7 exhibited cytotoxicity against PANC-1, K562, and BxPC-3, with IC50 values of 4.67, 0.72, and 4.01 μg/ml, respectively, whereas 8 was inactive against these cancer cell lines. The structureactivity relationship of compound 7 and 8 indicated that the 3′-OH group in polymethoxyflavonoids is essential for antitumor activity.

New Cytotoxic Metabolites from the Marine‐Derived Fungus Penicillium sp. ZLN29

Abstract: One new penicillide derivative, prenpenicillide (1), and one new xanthone derivative, prenxanthone (2), were isolated from the culture extract of the marine-derived fungus Penicillium sp. ZLN29, together with six known polyketide compounds, 3–8. Their structures were elucidated on the basis of spectroscopic and spectrometric analyses. The cytotoxicities of these eight compounds were evaluated on four tumor-cell lines by SRB (=sulforhodamine B) or MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) methods. Compounds 1 and 3 exhibited weak cytotoxicities against HepG2 cell line with IC50 values of 9.9 and 9.7 μM, respectively.

Organic Stereochemistry. Part 2

Abstract: This review continues a general presentation of the principles of stereochemistry with special reference to medicinal compounds. Here, we explore stereoisomeric compounds characterized by a single or several stereogenic centers (often also called centers of chirality). The main focus will be on chiral tetrahedral structures, namely a) tetracoordinate centers, and b) tricoordinate centers where an electron lone pair plays the role of the fourth substituent, forming a tetrahedron. Following an overview of the main tetrahedral structures of interest in biological and medicinal stereochemistry, the review places emphasis on explaining the two dominant conventions, namely the d,l- and (R,S)-convention, the latter being known as the CIP (CahnIngoldPrelog) convention. The review ends with a discussion of reactions of stereoisomerization at stereogenic C-centers and its relevance to drug research.

Unusual Spirodecane Sesquiterpenes and a Fumagillol Analogue from Cordyceps ophioglossoides

Abstract: Investigation of the cultured mycelia of Cordyceps ophioglossoides resulted in the isolation and characterization of three new unusual spiro[4.5]decane sesquiterpenes, cordycepol A (1), cordycepol B (2), and cordycepol C (3), and a new fumagillol analogue, cordycol (4). Their structures were established by spectroscopic means. The cytotoxic activities were also evaluated, compounds 3 and 4 showing their IC50 values in the range of 1233 mu g/ml against HeLa and HepG2 (Table 3). In addition, 3 and 4 were not obviously harmful towards normal liver cell lines LO2, showing IC50 values above 80 mu g/ml.

Two New Secoanthraquinone Derivatives from the Marine-Derived Endophytic Fungus Aspergillus wentii EN-48

Abstract: Two new secoanthraquinone derivatives, wentiquinones A (1) and B (2), together with the eight known compounds 310, were isolated from the culture extracts of Aspergillus wentii EN-48, an endophytic fungus derived from an unidentified marine brown algal species of the genus Sargassum. The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis.

Organic stereochemistry. Part 4 : isomerisms about single bonds and in cyclic systems

Abstract: This Part 4 continues a general presentation of the principles of stereochemistry with special reference to medicinal compounds and their interactions with biological systems. Here, we discuss and illustrate two major aspects of conformational isomerism, namely a) the concept of torsional isomerism about single bonds, and b) the intertwined conformational and configurational aspects of the stereochemistry of cyclic systems. The review begins with a brief reminder of the history and thermodynamics of conformational isomerism, and goes on to explain and illustrate the conventions and graphical representations used for conformers. Examples are then examined, beginning with ethane, the simplest one, and building up to more complex cases, documenting the attractive or repulsive role of substituents. A similar approach is applied when dealing with cyclic systems, although here the presentation necessarily takes into account configurational aspects specific to cyclic systems. The pharmacological implications of the concepts discussed here will be presented in Part 6.

Synthesis and Metal Complexes of Thiourea Ligands Containing Carbohydrate‐Derived Substituents

Abstract: Two glucose-derived thiourea derivatives, 2a and 2b, were prepared by addition of the corresponding amino sugars to a solution of 4-nitrobenzoyl isothiocyanate (Scheme 1). The thioureas were isolated as colorless solids in good yields and were fully characterized by NMR spectroscopy, optical rotation, elemental analysis, and also by single-crystal X-ray diffraction. Attempts to obtain CuII and NiII bis(chelate) complexes with these thioureas failed. However, the C(1)-protected thiourea derivative 2a reacted with orthopalladated acetato-bridged dimers to afford the corresponding monomeric PdII complexes 3 and 4 (Scheme 2). In these compounds, the thiourea coordinates to the metal as monoanionic O,S chelate ligand, which was confirmed by X-ray crystallography.

Synthesis of Isoindolo[2,1‐a]quinazoline‐5,11‐dione Derivatives via the Reductive One‐Pot Reaction of N‐Substituted 2‐Nitrobenzamides and 2‐Formylbenzoic Acids

Abstract: Various isoindolo[2,1-a]quinazoline-5,11-dione derivatives 3 were synthesized in good yields by means of the reductive reaction of N-substituted 2-nitrobenzamides 1 and 2-formylbenzoic acids 2 in the presence of SnCl2⋅2 H2O under reflux in EtOH (Scheme, Table). The procedure needed two steps, the reduction of the nitro group of the 2-nitrobenzamide and ring closure by nucleophilic addition of the NH2 group to both the formyl and carboxylic acid CO groups.

Synthesis of Natural Atisane‐Type Diterpenoids by retro‐Biomimetic Transformations

Abstract: An efficient one step, retro-biomimetic procedure for the synthesis of natural products having the atisane structure is described (Scheme 2), natural products which are components of medicinal plants and possess relevant biological activity. Their structures were confirmed by chemical transformations and spectral data. The starting materials were the known ent-kaur-16-en-19-oic acid (1) and ent-trachyloban19-oic acid (2), diterpenoids readily available from the waste of sunflower.

New Triterpenes from Gymnema sylvestre

Abstract: Phytochemical investigation of the aerial parts of Gymnema sylvestre has led to the isolation of seven new triterpenes, six oleane types (5, 7–11) and a new lupane type (12), and of the six known analogues 1–4, 6, and 13. The structures and relative configurations of these compounds were elucidated by spectroscopic analyses, including 1D- and 2D-NMR spectroscopy and mass spectrometry, and by the comparison of their NMR data with those of related compounds.

One‐Pot Synthesis of Dispiro[oxindole‐3,3′‐pyrrolidines] by Three‐Component [3+2] Cycloadditions of in situ‐Generated Azomethine Ylides with 3‐Benzylidene‐2,3‐dihydro‐1H‐indol‐2‐ones

Abstract: An efficient one-pot, three-component synthesis of novel dispiro[oxindole-3,3′-pyrrolidines] by 1,3-dipolar cycloaddition of azomethine ylides, in situ generated by reaction of 1,2-diones with sarcosine and subsequent decarboxylation, with a series of (E)-3-benzylidene-2,3-dihydro-1H-indol-2-ones is reported. Molecular complexity is generated in only one synthetic step. All reactions proceed with excellent regioselectivity and in good-to-excellent yields. The workup is easy, the reaction times are short, and no catalyst is required.

One‐Pot Synthesis of 5,7,8,9,9a,10‐Hexahydro‐8‐thioxotetrahydropyrido[2,3‐d : 6,5‐d′]dipyrimidine‐2,4,6(1H,3H,5aH)‐triones via a Four‐Component Coupling Reaction of Aldehydes, Amines, Barbituric Acids, and Thiouracil

Abstract: An efficient one-pot approach to the synthesis of 5,7,8,9,9a,10-hexahydro-8-thioxopyrido[2,3-d : 6,5-d′]dipyrimidine-2,4,6(1H,3H,5aH)-triones 5 via a four-component reaction of an aldehyde 1, an amine 2, a barbituric acid 3, and thiouracil (4) is reported for the first time. This new multicomponent reaction is accomplished in refluxing EtOH in the presence of tungstophosphoric acid (H3PW12O40) as a catalyst. A variety of hexahydropyrido[2,3-d : 6,5-d′]dipyrimidinetrione derivatives were successfully synthesized in excellent yields with this protocol (Table 2).

Two New Indole Alkaloids from Emmenopterys henryi

Abstract: Two new indole alkaloids, 5-oxodolichantoside (1) and deglycocadambine (2), were isolated from the twigs and leaves of Emmenopterys henryi, together with four known indole alkaloids and five known iridoids. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses, including 1D- and 2D-NMR experiments, and confirmed by single-crystal X-ray diffraction studies. This is the first report on the isolation of indole alkaloids from this species. The indole alkaloids were evaluated for their cytotoxic activities against five human cancer lines.

New 9,10-Secosteroids from Biotransformations of Bile Acids with Rhodococcus ruber

Abstract: Ofrom C(11) C(12) of secosteroids 4a and 4b affords the compounds 5a (5%) and 5b (20%), respectively.Onthe otherhand,in thebiotransformation of hyocholicacid with R.ruber the9,10-secosteroid4c is notdetected,but,rearrangingtoanintramolecularhemiacetalform,itevolvestothefinalfuranderivative6c(35%) by easy elimination of two molecules of H