A short synthesis of bisabolane sesquiterpenes

A facile total synthesis of three members of the bisabolane sesquiterpene family, namely (±)-curcumene, (±)-xanthorrhizol and (±)-curcuhydroquinone had been achieved in high overall yield. The synthesis used bromobenzene derivatives as starting materials. The halogen-lithium exchange followed by addition of isoprenylacetone and reduction of the obtained carbinols are the key steps of the synthetic pathway. This synthetic approach provides a new route to the bisabolane sesquiterpenes.     

(S)-(+)-姜黄烯的立体选择性全合成

利用不对称双羟化反应和Raney镍的原位还原,高对映选择性和高产率地实现了(S)-(+)-α-姜黄烯(1)的立体选择性合成.用MsCl保护化合物7a和7b时,发现了有趣的消除和重排反应,得到对应的二烯化合物8.     

Sesquiterpenoids from Costus Root Oil (Saussurea lappa CLARKE)

Apart from the well-known constituents (+)-β-selinene ( 2 ), (?)-β-elemene ( 4 ), (+)-β-costol ( 7 ), (?)-caryophyllene ( 17 ), and (?)-elemol ( 19 ) the following sesquiterpenoids have been isolated for the first time from costus root oil (Saussurea lappa CLARKE ): (?)-α-selinene ( 1 ), (+)-selina-4, 11-diene ( 3 ), (?)-α-trans-bergamotene ( 5 ), (?)-α-costol ( 6 ), (+)-γ-costol ( 8 ), (?)-elema-1,3,11 (13)-trien-12-ol ( 9 ), (?)-α-costal ( 11 ), (+)-γ-costal ( 12 ), (+)-γ-costal ( 13 ), (?)-elema-1,3,11 (13)-trien-12-al (elemenal, 14 ), (?)-(E)-trans-bergamota-2, 12-dien-14-al ( 15 ), (?)-ar-curcumene ( 16 ), and (?)-caryophyllene oxide ( 18 ). Compounds 6 , 8 , 9 , and 13 are new sesquiterpenoids. IR. and NMR. spectra of 12 sesquiterpenoids are reproduced.     

Enantioselective synthesis of orthogonally protected (2R,3R)-(−)-epicatechin derivatives,key intermediates in the de novo chemical synthesis of (−)-epicatechin glucuronides and sulfates

Ten orthogonally protected (?)-epicatechin and 3′- or 4′-O-methyl-(?)-epicatechin derivatives were prepared in a regiospecific and enantioselective manner. For each orthogonally protected (?)-epicatechin derivative, one specific phenolic hydroxyl was protected with a methoxymethyl (MOM) or p-methoxybenyzl (PMB) group and the remainder were protected as benzyl ethers. These uniquely protected (?)-epicatechin derivatives were designed to facilitate the regiospecific installation of a glucuronic acid or sulfate unit onto (?)-epicatechin after selective removal of the MOM or PMB protecting group to provide authentic standards of (?)-epicatechin glucuronides and sulfates.     

Asymmetric total synthesis of optically active α-curcumene

(R)-(?)-α-Curcumene has been prepared in 66% optical yield and in 34% overall yield in five steps by means of asymmetric Grignard cross-coupling reaction catalyzed by a nickel complex of chiral (aminoalkylferrocenyl)phosphine as a key carbon-carbon bond forming step.     

Synthesis and antibacterial activity of methylated N-(4-N,N-dimethylaminocinnamyl) chitosan chloride

The methylated chitosan containing different aromatic moieties were synthesized by two steps, the reductive amination and the methylation. The chemical structures of all methylated derivatives, methylated N-(4-N,N-dimethylaminocinnamyl) chitosan chloride (MDMCMCh), methylated N-(4-pyridylmethyl) chitosan chloride (MPyMeCh), and N,N,N-trimethyl chitosan chloride (TMChC) were characterized by ATR-FTIR and ¹H NMR spectroscopy. The molecular weights of the methylated chitosan derivatives were determined by gel permeation chromatography. The results revealed that the molecular weights of chitosan and N-aryl chitosan derivatives could be reduced by the methylation process. The degree of N-substitution (DS) and the degree of quaternization (DQ) were calculated by ¹H NMR ranged from 50% to 76%, and 28% to 82%, respectively. The water solubility of the methylated chitosan derivatives decreased with increasing concentration and pH. The antibacterial studies of these methylated chitosan derivatives were carried out by using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods against Escherichia coli ATCC 25922 (Gram-negative) and Staphylococcus aureus ATCC 6538 (Gram-positive) bacteria. It was found that the MDMCMCh showed higher antibacterial activity than TMChC while MPyMeCh exhibited reduced antibacterial activity against both bacteria at the same DQ level. In comparison to each of the chemical structure, it was found that the antibacterial activity was not only dependent on the DQ but it was also dependent on the positively charged location and the molecular weight.     

1,3-Dipolar cycloaddition of a chiral nitrone to (E)-1,4-dichloro-2-butene: a new efficient synthesis of (2S,3S,4R)-4-hydroxyisoleucine

1,3-Dipolar cycloaddition of a chiral nitrone derived from (?)-menthone to (E)-1,4-dichlorobut-2-ene was the key step in a novel 5 step synthesis of (2S,3S,4R)-4-hydroxyisoleucine, obtained in 21% overall yield with high enantiopurity.     

Organocatalytic Asymmetric Mannich Cyclization of Hydroxylactams with Acetals: Total Syntheses of (−)‐Epilupinine, (−)‐Tashiromine,and (−)‐Trachelanthamidine

An asymmetric, organocatalytic, one‐pot Mannich cyclization between a hydroxylactam and acetal is described to provide fused, bicyclic alkaloids bearing a bridgehead N atom. Both aliphatic and aromatic substrates were used in this transformation to furnish chiral pyrrolizidinone, indolizidinone, and quinolizidinone derivatives in up to 89 % yield and 97 % ee. The total syntheses of (?)‐epilupinine, (?)‐tashiromine, and (?)‐trachelanthamidine also achieved to demonstrate the generality of the process.     

One-step,stereoselective synthesis of octahydrochromanes via the Prins reaction and their cannabinoid activities

Novel, functionalized octahydrochromane derivatives were synthesized in a single step via the Prins reaction. Enantiomerically pure (+)-isopulegol was reacted with benzaldehyde to stereoselectively yield the corresponding octahydro-2H-chromen-4-ol derivative containing five stereocenters. A total of 10 compounds were synthesized by altering the enantiomer of isopulegol and the substituted benzaldehyde, and the resulting enantiopure octahydrochromanes were screened in vitro against the cannabinoid receptor isoforms CB1 and CB2. Compounds containing an olefin at the C4 position [(+)-3c, (?)-3c, (?)-7c, (?)-9c and (?)-11c] of the octahydrochromane scaffold were found to exhibit reasonable displacement of [³H] CP55,940 from the CB receptors, whereas the corresponding hydroxy analogs [(+)-3a, (+)-3b, (?)-3a, (?)-3b and (+)-5a] had very little or no effect.     

Microwave promoted synthesis and antimicrobial activity of 3-thiazole substituted 2-styryl-4(3H)-quinazolinone derivatives

The present paper describes an optimized reaction condition for the microwave promoted synthesis of newer 3-thiazole substituted 2-styryl-4(3H)-quinazolinone derivatives, which in turn were prepared in good yield by the treatment of various 2-styryl benzoxazinone derivatives with various 2-aminothiazoles using co-solvent under microwave irradiation. All the compounds were characterized by various spectroscopic techniques and analytical methods. All newly synthesized compounds have been screened for their in vitro antibacterial and antifungal activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus megaterium,Bacillus subtilis, and Aspergillus niger.     

Asymmetrische Synthese von L-γ-Carboxyglutaminsäure-Derivaten

Asymmetric synthesis of L -γ-carboxyglutamic acid derivatives A modified Strecker synthesis according to Patel & Worsley was used to prepare γ,γ′-di-t-butyl L (?)-N-phthaloyl-γ-carboxyglutamate with almost 100% optical purity and an overall yield of about 10% relative to di-t-butyl malonate, or 20% relative to (?)-α-methyl-benzylamine (s. Scheme).     

Catalytic Asymmetric Construction of α‐Quaternary Cyclopentanones and Its Application to the Syntheses of (−)‐1,14‐Herbertenediol and (−)‐Aphanorphine

A novel and efficient strategy to build α‐benzylic quaternary cyclopentanones with excellent enantioselectivities (up to 96 % ee) and high yields (up to 99 % yield) has been developed, and its application demonstrated by the first catalytic asymmetric total synthesis of (?)‐1,14‐herbertenediol and the formal synthesis of (?)‐aphanorphine.     

Engineering quaternized chitosan in the 3D bacterial cellulose structure for antibacterial wound dressings

Balancing antibacterial properties with biocompatibility is of paramount importance for wound dressings loaded with antibacterial agents. In this work, a water soluble antibacterial agent, quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) with an appropriate degree of substitution was introduced into the bacterial cellulose (BC) network by adding it into the BC culture medium. Results indicated that the addition of HACC could affect the yield of BC, porous structure, thermal stability, water absorption and antibacterial properties. HBC-1 with a low content of HACC (13.65 ± 0.30%) cannot inhibit the biofilm formation of bacteria, while HBC-3 with a high content of HACC (62.05 ± 0.90%) has a low yield of BC and confused structure. HBC-2 with an optimum concentration of HACC (37.33 ± 0.80%) possessed a typical porous structure, acceptable thermal stability, good water absorption and favorable antibacterial properties against Staphylococcus aureus (S. aureus, ATCC 25923) and methicillin-resistant S. aureus (ATCC 43300). Most importantly, none of the HACC/BC films exhibited cytotoxicity to NIH3T3 cells. We believe that obtained HACC/BC films with favorable bactericidal properties and biocompatibility could be potential candidates for wound dressings in clinical applications.     

Antibacterial activity of methylated chitosan and chitooligomer derivatives: Synthesis and structure activity relationships

The purpose of this study was to synthesize series of methylated chitosaccharide derivatives, possessing various degree of methylation, and to determine their structure activity relationship (SAR) with regard to their antibacterial effect against Staphylococcus aureus. Chitosan polymer and chitooligomers were used as starting materials and were methylated by reaction with methyl iodide. Depending on the reaction conditions the degree of N-quaternization ranged from 0% to 74%, with varying degree of N,N-dimethylation, N-monomethylation and O-methylation. More selective N-quaternization could be obtained with protection group strategy. At pH 5.5 the chitosaccharide polymers and their methylated derivatives were active against S. aureus with minimal inhibitory concentration (MIC) ranging from 16 to 512 μg/mL. At pH 7.2 the non-quaternized derivatives were inactive but their highly N-quaternized derivatives showed MIC as low as 8 μg/mL. The chitooligomers, as well as their derivatives, were inactive at both pH’s. The SAR studies revealed that N-quaternization was mainly responsible for the antibacterial effects at pH 7.2, whereas it did not contribute to the antibacterial activity under acidic conditions.     

Cycloaddition of a chiral nitrone to allylic motifs: an access to enantiopure sugar-based amino acids displaying a stable glycosidic bond and to 4(S)-4-hydroxy-l-ornithine

A (?)-menthone-derived nitrone and various allyl O-, and S-glycosides reacted at 110 °C to afford the corresponding cycloadducts in good yields. For an N-acetylated allyl N-glycoside, an N-glycoside-based product was formed in poor yield with loss of the N-acetyl residue, while the major product 4 (60%), in which the sugar moiety was absent, arose from cleavage of the N-glycosidic bond, under the cycloaddition conditions. The cycloadducts of the O-, and S-glycoside type were ring-opened and subjected to acidic and basic hydrolysis, for removing the chiral auxiliary. This resulted in glycosidic bond cleavage for O-glycosides and loss of material, while an S-glycoside amino acid was isolated in 78% yield, indicating a higher resistance of the S-glycosidic bond. N–O Bond cleavage and hydrolytic treatments applied to 4 afforded 4(S)-4-hydroxy-l-ornithine in high yield. Use of the nitrone derived from (+)-menthone should afford the enantiomer of 4, both precursors of 4-hydroxy arginine derivatives by guanidination.     

A flexible enantioselective approach to 3,4-dihydroxyprolinol derivatives by SmI2-mediated reductive coupling of chiral nitrone with ketones/aldehydes

A flexible enantioselective approach to polyhydroxylated prolinol derivatives was described, which is based on the samarium diiodide-mediated reductive coupling of the chiral nitrone (3S,4R)-8, derived from d-isoascorbic acid with aldehydes/ketones. Thereby, polyhydroxyprolinol derivatives 9a–e and 9h–j were obtained from aromatic ketones and aliphatic aldehydes in good to excellent yields of 65–91%. These reductive hydroxyalkylations are highly diastereoselective in establishing the C-4 stereogenic center. By this way, the asymmetric syntheses of (?)-8a-epi-swainsonine (4) and (?)-8,8a-di-epi-swainsonine (5) have been achieved.     

Preparation of chiral trans-5-substituted-acenaphthene-1,2-diols by baker’s yeast-mediated reduction of 5-substituted-acenaphthylene-1,2-diones

A series of trans-5-substituted-acenaphthene-1,2-diols were obtained in 21–72% yield with 97–100% ee by baker’s yeast-mediated reduction of the corresponding acenaphthylene-1,2-diones, in the presence of DMSO as a co-solvent and under vigorous agitation. The absolute configuration of (?)-trans-5-methoxy-acenaphthene-1,2-diol trans-3b and (?)-trans-5-bromo-acenaphthene-1,2-diol trans-3c was assigned as (S,S) and (?)-trans-5-thiomorpholin-acenaphthene-1,2-diol trans-3d was established as (R,R) by exciton-coupled circular dichroism.     

Prediction of the antimicrobial activity of quaternary ammonium salts against Staphylococcus aureus using artificial neural networks

The study of the quantitative structure–activity relationship (QSAR) on antibacterial activity in a series of new imidazole derivatives against Staphylococcus aureus was conducted using artificial neural networks (ANNs). Antibacterial activity against S. aureus was associated with a number of physicochemical and structural parameters of the examined imidazole derivatives. The designed regression and classification models were useful in determining the antibacterial properties of quaternary ammonium salts against S. aureus. The developed models of artificial neural networks were characterized by high predictability (93.57% accuracy of classification, regression model: training data R = 0.92, test data R = 0.92, validation data R = 0.91). ANNs are considered to be a useful tool in supporting the design of synthesis and further biological experiments in the logical search for new antimicrobial substances. Data analysis using ANNs enables the optimization and reduction of labor costs by narrowing the compound synthesis to achieve the desired properties.     

High antibacterial activity and low toxicity of pyridoxal derivatives of chitosan and their nanoparticles

The pyridoxal derivatives of chitosan with various degrees of substitution (DS) were synthesized from low-, moderate- and high-molecular-weight chitosans by their reaction with pyridoxal followed by treatment with NaBH₄. The derivative of moderate molecular weight and high DS demonstrated a maximum antibacterial activity against S. aureus and E. coli. The nanoparticles of this derivative obtained by ionic gelation are nontoxic, and they exhibit a high in vitro antibacterial effect, which slightly exceeds that of ampicillin and gentamicin.     

Seasonal and chemotype influences on the chemical composition of Lantana camara L.: Essential oils from Madagascar

Yellow-orange and pink-violet colours of flower plants of Lantana camara from Madagascar were studied with a focus on essential oil (EO) in order to characterize chemotype EO variability. The chemical composition of 73 samples of aerial part EO of L. camara collected each month of the year, at various location, have been characterized by gas chromatography-mass spectrometry (GC-MS). Among the 50 peaks characterized, 43 were identified. The main components changed within the two flower colour types. EO from yellow-orange colour of flowers compared to pink-violet flowers is characterized by high content in terpenic compounds and lower amount in oxygenated compounds. Similar results were observed during seasons, showing that the chemical composition is relatively stable all year long. The components characterizing the pink-violet flower chemotype are: sabinene (9.4-11.3%), 1,8-cineole (3.7-4.6%), linalool (4.8-6.1%), β-caryophyllene (11.3-13.6%), α-humulene (4.4-5.2%), β-bisabolene (1.7-2.3%), γ-cadinene (0.1-0.4%), ar-curcumene (1.0-1.6%), caryophyllene oxide (1.2-0.7%) and davanone (22.6-25.9%). The components characterizing the yellow-orange flower chemotype are: sabinene (9.0-14.3%), 1,8-cineole (0.8-1.0%), linalool (0.4-1.4%), β-caryophyllene (25.8-30.8%), α-humulene (2.4-2.6%), β-bisabolene (13.6-14.9%), γ-cadinene (0.6-5.2%), ar-curcumene (0.7-2.8%), caryophyllene oxide (0.1-0.4%) and davanone (0.0-0.6%). Chemical composition of nine L. camara industrial EO show that they are composed of mixture of yellow-orange and pink-violet colour of flower chemotypes. Davanone is found in all samples with a mean of 12.4%, linalool (5.4%) and 1,8-cineole (4.1%). For sesquiterpenes, the main are β-caryophyllene (15.9%), β-bisabolene (1.8%) and γ-muurolene (1.4%).