Palladium-catalyzed approach for the general synthesis of (E)-2-arylmethylidene-N-tosylindolines and (E)-2-arylmethylidene-N-tosyl/nosyltetrahydroquinolines: access to 2-substituted indoles and quinolines.

A facile and efficient method for the synthesis of (E)-2-arylmethylidene-N-tosylindolines and (E)-2-arylmethylidene-N-tosyl/nosyltetrahydroquinoline variants has been developed through palladium-catalyzed cyclocondensation of aryl iodides with readily available 1-(2-tosylaminophenyl)prop-2-yn-1-ols and their higher homologues, respectively. The proposed reaction mechanism invokes the operation of trans-aminopalladation during cyclization (5/6-exo-dig), which ensures exclusive (E)-stereochemistry in the products. The method is fast, operationally simple, totally regio- and stereoselective, and versatile enough to access a variety of 2-substituted indoles and quinolines. The reactions proceeded efficiently with a wide variety of substrates and afforded the corresponding products in moderate to excellent yields.

Fluorescent pigment and phenol glucosides from the heartwood of Pterocarpus marsupium.

The fluorescence shown by extracts of the heartwood of Pterocarpus marsupium is attributed to salts of the new compound 1, whose structure was elaborated using detailed spectroscopic/spectrometric studies. The plant material also contains the nonfluorescent compounds 2 and 3. The absolute configuration of 1 was determined by experimental and theoretically calculated electronic CD spectra, while that of 3 was deduced from ECD comparison with reported results in the α-hydroxydihydrochalcone series.

A rapid and facile method for the general synthesis of 3-aryl substituted 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrazines and their ring fused analogues.

We report a general and facile method that provides rapid entry into 3-aryl substituted 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrazines and their ring fused analogues in one-pot under palladium-copper catalysis. The methodology utilises simple and easily available substrates of broad range. The applicability of this reaction for the synthesis of optically active products has been demonstrated. A plausible reaction mechanism has also been proposed.

A novel galacto-glycerolipid from Oxalis corniculata kills Entamoeba histolytica and Giardia lamblia.

Oxalis corniculata is a naturally occurring weed that has been used in traditional medicine for the cure of dysentery and diarrhea in India. One of the common causes of dysentery is due to infection by the protist pathogen Entamoeba histolytica. Bioactivity profiling of extracts from O. corniculata identified several compounds that showed antiamoebic activity in axenic cultures of E. histolytica. These were characterized by nuclear magnetic resonance, infrared, and mass spectrometry as (i) Oc-1, a mixture of saturated fatty acids C24 to C28; (ii) Oc-2, a mixture of long-chain alcohols C18 to C28; and (iii) Oc-3, a single compound that was a galacto-glycerolipid (GGL). Of the different compounds that were obtained, the strongest antiamoebic activity was found in GGL. The addition of GGL to E. histolytica xenic cultures containing other microbial flora from the large intestine did not affect its antiamoebic activity. Amoebicidal concentrations of GGL had no effect on intestinal microbial flora or on the mammalian cell line HEK-293. GGL was also found to be equally effective in killing another protist pathogen, Giardia lamblia, that causes diarrhea in humans. The importance of this study is based on the identification of novel natural products and the possibility of developing these compounds as active agents to treat at least two pathogenic parasitic intestinal infections endemic to tropical regions.

Locked nucleosides based on oxabicyclo[3.2.1]octane and oxabicyclo[2.2.1]heptane skeletons.

Intramolecular nitrone cycloaddition (INC) reaction on a d-glucose derived substrate carrying an allyl group at C-1 and an enose-nitrone at C-5 or an aldehyde-nitrone at C-1 and vinyl group at C-4 furnished a tricyclo[6.2.1.0(2,6)]undecane or a tricyclo[5.2.1.0(2,6)]decane ring structure. These tricycles were converted to bicylic nucleosides with oxabicyclo[3.2.1]octane and oxabicyclo[2.2.1]heptane rings in three steps. An oxabicyclo[3.2.1]octane ring compound could alternatively be formed by RCM reaction between C-1-allyl and C-4-vinyl moieties and transformed to nucleoside analogues through a nucleophilic substitution reaction. Participation of a neighboring benzyl ether substituent in one case paved the way for an enantiodivergent synthesis.

An expedient and facile route for the general synthesis of 3-aryl substituted 1,2,3-triazolo[1,5-a][1,4]benzodiazepin-6-ones and 1,2,3-triazolo[1,5-a][1,5]benzodiazocin-7-ones.

We describe herein a convenient approach for the general synthesis of novel tricyclic scaffolds incorporating a fusion of the 1,2,3-triazole ring with difficultly obtainable medium sized rings such as [1,4]benzodiazepin-5-ones and [1,5]benzodiazocin-6-ones through Sonogashira coupling of an aryl iodide with 2-amino-N-methyl-N-(prop-2-ynyl)benzamide or homologue followed by in situ diazotisation, azidation and cycloaddition reactions. The strategy also allows easy accessibility of the corresponding amide-reduced analogues. The operational simplicity and easy substrate availability make the process cost effective and practical.

Expedient and rapid synthesis of 1,2,3-triazolo[5,1-c]morpholines through palladium-copper catalysis.

A one-pot approach using palladium-copper as catalyst has been developed for the synthesis of morpholines fused with 1,2,3-triazole. Good regioselectivity, mild reaction conditions, high yields and short reaction time are the hallmarks of this method.

First example of 5/6-O-linked pseudosaccharides: synthesis of bicyclic nucleosides containing azido or extended carbohydrate moiety.

Treatment of the d-glucose-derived substrate 1 with sodium hydride in tetrahydrofuran provided 3,6-anhydro monosaccharide 2, along with the 5,6-ether linked pseudodisaccharide 3, and pseudotrisaccharide 4. However, reaction of 1 with sodium ethoxide in ethanol afforded 2 as the sole product, elaborated to the bicyclic azidonucleosides 9 and 16. Acetylated bicyclic nucleosides 17-19 with extended carbohydrate residues have been synthesized from 3.

Woodfordia fruticosa: traditional uses and recent findings.

Woodfordia fruticosa Kurz of the family Lythraceae is a plant of tropical and subtropical region with a long history of medicinal use. A wide range of chemical compounds including tannins (especially those of macrocyclic hydrolysable class), flavonoids, anthraquinone glycosides, and polyphenols have been isolated from this species in recent times. Extracts and metabolites of this plant, particularly those from flowers and leaves, possess useful pharmacological activities. A comprehensive account of the chemical constituents and the biological activities is presented and a critical appraisal of the ethnopharmacological issues is included in view of the many recent findings of importance on this plant.

Glucosides from Curculigo orchioides.

From the rhizomes of Curculigo orchioides two phenolic glucosides named orchiosides A and B were isolated besides four known compounds and their structures were elucidated by the combination of 2D-NMR analysis, mass spectrometry and chemical evidences.

Hopane-type saponins from Glinus lotoides Linn.

Seven hopane-type saponins were isolated from the methanol extract of Glinus lotoides. Six of them were identified as novel compounds and designated as lotoideside A [3-O-beta-D-xylopyranosyl (1-->2)-alpha-L-rhamnopyranosyl-6 alpha-O-beta-D-xylopyranosyl-22-beta-O-beta-D-glucopyranosyl-16 beta-hydroxy hopane (1)], lotoideside B [3-O-beta-D-xylopyranosyl (1-->2)-alpha-L-rhamnopyranosyl-22-beta-O-beta-D-glucopyranosyl-6 alpha,16 beta-dihydroxyhopane (2)], lotoideside C [3-OD-xylopyranosyl-6 alpha-O-beta-D-xylopyranosyl-16 beta-O-beta-D-xylopyranosyl-22 beta-hydroxyhopane (3)], lotoideside D [3-O-beta-D-xylopyranosyl-16 beta-O-alpha-L-arabinopyranosyl-6 alpha,22-beta-dihydroxyhopane (4)], lotoideside E [3-O-beta-D-xylopyranosyl-6 alpha-O-beta-D-xylopyranosyl-16 beta,22-beta-dihydroxyhopane (5)], and lotoideside F [3-O-beta-D-xylopyranosyl-22-beta-O-beta-D-glucopyranosyl-16 beta-hydroxyhopan-6-one (6)]. The known compound succulentoside B (7) was also encountered. Their structures were elucidated on the basis of one-and two-dimensional NMR spectroscopic techniques, ESIMS and chemical evidences.

Bicyclic nucleoside analogues from D-glucose: synthesis of chiral as well as racemic 1,4-dioxepane ring-fused derivatives.

The dioxepanofuranose derivatives 4 and 12, obtained through the cyclization of the 3-(2-hydroxyethyl) ether of a D-xylo-pentodialdose derivative, were appropriately functionalized and elaborated to the first examples of the new class of 3'-O and 5'-O-bicyclic nucleoside analogues 9, 10, and 14 with a fused seven-membered ring. Reactions carried out through the intermediacy of the D-xylo-pentodialdose derivative 5 yielded racemic products, while prior protection of the 4-formyl group (as in 7) before deprotection of the 1,2-hydroxyl groups led to optically active analogues.

First total synthesis of the 4a-methyltetrahydrofluorene diterpenoids (+/-)-dichroanal B and (+/-)-dichroanone.

[reaction: see text] A simple synthesis of the 4a-methyltetrahydrofluorene diterpenoids (+/-)-dichroanal B and (+/-)-dichroanone has been achieved through a common hexahydrofluorenone intermediate obtained via Pd(0)-catalyzed reductive cyclization of a substituted 2-(2-bromobenzyl) methylene cyclohexane.

Oxorhenium(V) and Oxotechnetium(V) Complexes of Cysteine.

Earlier attempts to obtain technetium complexes with cysteine always resulted in the formation of a product contaminated with polymeric species. A pure product, which could be chemically characterized and adopted for radiopharmaceutical preparation, has now been obtained by using cystine as the precursor of cysteine. This method has been extended to prepare the corresponding rhenium chelate, isolated as the tetraphenylphosphonium salt [Ph(4)P](+)[{ReO(Cys)(2)}(-){HReO(Cys)(2)}].4H(2)O. The X-ray crystal structure of this compound revealed the presence of both neutral and anionic chelated species. In [HReO(Cys)(2)], the cysteine carboxylate moiety is unidentatedly bound to rhenium, while the carboxylic acid of the second cysteine remains as free COOH. The coordination environment around rhenium in the anionic species [ ReO(Cys)(2)(-)] is similar, the only difference being that the uncoordinated carboxylate moiety is present as a COO(-) anion. The thiolate, amine coordination of the ligand with the metal is present in both the chelate units. The compound crystallized in an orthorhombic system with the space group P2(1)2(1)2(1), and having four formula units in each cell. The crystal data are a = 9.700(2) Å, b = 12.836(3) Å, and c = 36.228(3) Å. The rhenium chelate has been structurally correlated with the technetium chelates through comparable spectroscopic and chromatographic data. The technetium-99m analogue of this rhenium chelate exhibited renal tubular transport and renal retention, which makes this radiopharmaceutical useful for evaluation of the clinical status of renal patients.

Rational construction of triazole/urea based peptidomimetic macrocycles as pseudocyclo-ß-peptides and studies on their chirality controlled self-assembly.

A tandem macro-dimerization reaction via a Cu(I) catalyzed azide/alkyne cycloaddition reaction has been employed to construct triazole/urea based peptidomimetic macrocycles considered as pseudocyclo-ß-peptides. Introduction of one particular chirality in the peptide backbone can alter the conformation as well as nature of self-assembly from cyclic D-,L-,α-peptide to cyclo-ß-peptide. One of them (16a) forms antiparallel dimers while the other (16b) undergoes higher order aggregation to form a nanorod structure.

Design and synthesis of regioisomeric triazole based peptidomimetic macrocycles and their dipole moment controlled self-assembly.

Two peptidomimetic macrocycles, regioisomeric in terms of the position of triazole/amide, have been synthesized. Both undergo self-assembly in a parallel manner but in solvents of opposite polarity, ascribed to (ß, ß) and (ß-D, ß-L) hydrogen bonding leading to formation of two different unique classes of organic nanostructures.

Interaction of aristololactam-ß-D-glucoside and daunomycin with poly(A): spectroscopic and calorimetric studies.

The binding of two sugar containing antibiotics viz. aristololactam-ß-D-glucoside and daunomycin with single and double stranded poly(A) was investigated by spectroscopic and calorimetric studies. The binding affinity of daunomycin to ss poly(A) was of the order of 106 M⁻¹ and that to ds poly(A) was of the order of 105 M⁻¹. Aristololactam-ß-D-glucoside showed a relatively weaker binding with an affinity of the order of 104 M⁻¹ with both the conformations of poly(A). Fluorescence studies showed maximum quenching for daunomycin-ss poly(A) complexes. The binding constants calculated from fluorescence spectroscopy were in good agreement with that obtained from UV spectroscopy. Moderate perturbation of circular dichroic spectra of both the conformations of poly(A) in presence of these molecules with concomitant formation of prominent extrinsic CD bands in the 300-450 nm region further revealed the association. Isothermal titration calorimetry results showed an overall entropy driven binding in all the four systems though the entropy change was maximum in daunomycin-ss poly(A) binding. The binding affinity was also maximum for daunomycin-ss poly(A) and varied as daunomycin-ds poly(A) > aristololactam-ß-D-glucoside-ds poly(A) > aristololactam-ß-D-glucoside-ss poly(A). A 1:1 binding stoichiometry was observed in all the cases, as confirmed by Job plot analysis, indicating the interaction to consist of a single binding mode. Ferrocyanide quenching studies showed good stacking interaction in all cases but was best for daunomycin-ss poly(A) interaction. No self-structure formation was observed in poly(A) with both daunomycin and aristololactam-ß-D-glucoside suggesting the hindrance of the sugar moiety for such structural organization.

Simultaneous parallel and antiparallel self-assembly in a triazole/amide macrocycle conformationally homologous to D-,L-α-amino acid based cyclic peptides: NMR and molecular modeling study.

A 1,4-linked triazole/amide based peptidomimetic macrocycle, synthesized from a triazole amide oligomer of cis-furanoid sugar triazole amino acids, possesses a conformation resembling the D-,L-α-amino acid based cyclic peptides despite having uniform backbone chirality. It undergoes a unique mode of self-assembly through an antiparallel backbone to backbone intermolecular H-bonding involving amide NH and triazole N2/N3 as well as parallel stacking via amide NH and carbonyl oxygen H-bonding, leading to the formation of a tubular nanostructure.

Introduction of vinyl and hydroxymethyl functionalities at C-4 of glucose-derived substrates: synthesis of spirocyclic, bicyclic, and tricyclic nucleosides.

Installing hydroxymethyl and hydroxyethyl substitutions at C-4 through vinylation and hydroboration-oxidation reactions of the C-4 bis-hydroxymethyl derivative of d-glucose based substrate, and inserting heteroatoms thereafter permitted formation of N-, O-, or S-heterocycles leading to [4,5]- or [5,5]-spirocycles and a bicyclo[3.3.0]octane product. Some of the spirocycles were converted to spironucleosides under Vorbruggen glycosidation reaction conditions. Similarly, the bicyclic product was elaborated to the corresponding bicyclic nucleoside as well as an unexpected tricyclic nucleoside.

Synthesis of oxepane ring containing monocyclic, conformationally restricted bicyclic and spirocyclic nucleosides from D-glucose: a cycloaddition approach.

Carbohydrate-derived substrates having (i) C-5 nitrone and C-3-O-allyl, (ii) C-4 vinyl and a C-3-O-tethered nitrone, and (iii) C-5 nitrone and C-4-allyloxymethyl generated tetracyclic isoxazolidinooxepane/-pyran ring systems upon intramolecular nitrone cycloaddition reactions. Deprotection of the 1,2-acetonides of these derivatives followed by introduction of uracil base via Vorbrüggen reaction condition and cleavage of the isooxazolidine rings as well as of benzyl groups by transfer hydrogenolysis yielded an oxepane ring containing bicyclic and spirocyclic nucleosides. The corresponding oxepane based nucleoside analogues were prepared by cleavage of isoxazolidine and furanose rings, coupling of the generated amino functionalities with 5-amino-4,6-dichloropyrimidine, cyclization to purine rings, and finally aminolysis.