Elaeodendron orientale as a source of cytotoxic cardenolides.

In the present study, we report six cardiac glycosides (1-6) along with four known ones (7-10) isolated from the leaves and fruits of Elaeodendron orientale. Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR, and the absolute configuration of 1 was determined by X-ray diffraction analysis. The compounds were evaluated for growth inhibitory activity against a panel of human cancer cell lines, HeLa, A-549, MCF-7 and HL-60, and normal Vero cells. Four compounds from this series (5 and 7-9, IC50 values ranging from 0.01 to 0.07µM) exhibited cytotoxicity against three of the cancer cell lines assayed that was similar to or higher than the well-known therapies digoxin and digitoxigenin. Taking into account the narrow safety range of cardiac glycosides used in clinic, this series shows a selectivity index higher than 3 for three of the cancer cell lines assayed, increasing their interest for further study.

Defensive sesquiterpenes from Senecio candidans and S. magellanicus, and their structure-activity relationships.

Eleven eremophilanolides, 1-3 and 6-13, and two eremophilanes, 24 and 25, were isolated from Senecio candidans and S. magellanicus from the Magallanes Region (Chile). Compounds 2, 3, 9, and 10 have not been previously reported as natural products. Their structures were established by NMR spectroscopic analysis and chemical transformations. The X-ray analysis of compounds 11, 13, and 17 were also performed. Different semisynthetic analogs from eremophilanolide 11 were generated to carry out a structure-activity relationship study. Their possible plant defensive role was tested against herbivorous insects (Spodoptera littoralis, Rhopalosiphum padi, and Myzus persicae) and plants (Lactuca sativa). Additionally, their effects on insect (Sf9) and mammalian (CHO) cell lines were tested.

Intramolecular Nicholas reaction: stereoselective synthesis of 5-alkynylproline derivatives.

The intramolecular Nicholas reaction of propargylic alcohols derived from N, N-acyl-diprotected omega-semialdehydes obtained from glutamic acid provided stereoselectively 5-alkynylproline derivatives. The suitable choice of the N-protecting group (tosyl or benzoyl derivative) permitted control of the stereochemistry during the ring formation. Semiempirical calculations of the species involved in the cyclization support the observed stereochemistry.

Iron(III)-promoted aza-Prins-cyclization: direct synthesis of six-membered azacycles.

[reaction: see text] A new iron(III) halide-promoted aza-Prins cyclization between gamma,delta-unsaturated tosylamines and aldehydes provides six-membered azacycles in good to excellent yields. The process is based on the consecutive generation of gamma-unsaturated-iminium ion and further nucleophilic attack by the unsaturated carbon-carbon bond. Homoallyl tosylamine leads to trans-2-alkyl-4-halo-1-tosylpiperidine as the major isomer. In addition, the alkyne aza-Prins cyclization between homopropargyl tosylamine and aldehydes gives 2-alkyl-4-halo-1-tosyl-1,2,5,6-tetrahydropyridines as the only cyclic products.

Distinct dynamic behaviors of water molecules in hydrated pores.

Water molecules confined inside narrow pores are of great importance in understanding the structure, stability, and function of water channels. Here we report that besides the H-bonding water that structures the pore, the permanent presence of a significant, fast-moving fraction of incompletely H-bonded water molecules inside the pore should control the free entry and exit of water. This is achieved by means of complementary DSC and solid-state NMR studies. We also present compelling evidence from X-ray diffraction data that the cluster formed by six water molecules in the most stable cage-like structure is sufficiently hydrophobic to be stably adsorbed in a nonpolar environment.

Synthesis and structure of hydroxyl acids of general structure 7,7-alkenyl/alkynyl-5-hydroxymethyl-6-oxabicyclo[3.2.1]octane-1-carboxylic acid.

The open-ended hollow tubular structure formed by inclusion of water molecules in the packing of the hydroxyl acid 1 (R1 = CH2OH, R2 = ethyl groups) led to the synthesis and structural study of their unsaturated analogues. In this article we report on a general and practical large-scale synthesis of hydroxyl acids that possess alkenyl and alkynyl appendages. Substitution of the ethyl groups in 1 with unsaturated two-carbon appendages has a different effect on the molecular structure and on the hydrogen-bonding pattern. No variation has been induced by substitution of only one ethyl group with a vinyl one, although the substitution of both ethyl groups with vinyl or acetylene appendages has the greatest effect on the molecular structure and results in different hydrogen-bonding motifs.

Bioactive eremophilanolides from Senecio poepigii.

A new bioactive eremophilanolide, 1alpha-tigloyloxy-8betaH,10betaH-eremophil-7(11)-en-8alpha,12-olide, was isolated from Senecio poepigii and its structure was elucidated by spectral analysis. 1alpha-Angeloyloxy-8beta-methoxy-10betaH-eremophil-7(11)-en-8alpha,12-olide was also isolated. Antifungal and insect antifeedant properties were evaluated.

Water molecules in hydroxy/acid networks as a competition between dynamics and bonding. Synthesis of a wet hydrophobic pore.

In a model formed by hydroxy acids with a general structure (+/-)-1, we found that solid-state structures depend on steric interactions. Thus, with the exception of molecules 1b and 1e, compounds (+/-)-1a-(+/-)-1m, which possess bulky and conformationally rigid substituents, aggregate by forming tapes and sheets by alternating (+) and (-) subunits held together via carboxylic acid to alcohol hydrogen bonds. Homologue (+/-)-1n with conformationally flexible substituents, which allow conformational deformation gives, by way of the incorporation of water molecules, an efficient hexagonal assembly, which extends to the third-dimension to form tubular H-bonding networks. Each puckered channel can be described as being interconnected by closely packed hexagons in chair-like conformations. The ethyl groups presented in (+/-)-1n provided the volume required to lock the inner hexagonal wall into a rigid structure.

Cause of hydration/dehydration in condensed organic materials: synthesis of hydrophobic pores.

[reaction: see text] The unique solid-state hydration/dehydration properties of the diacid (+/-)-1e in comparison with other homologues of the same family are studied. Hydrophobic enhancement, which is a consequence of the loss of water molecules from (+/-)-1e chains, is a property that can be exploited to achieve organic condensed systems for nonpolar molecules by interstitial van der Waals confinement.

Rhoiptelenol and rhoiptelenone, two pentacyclic triterpenes from Sideritis macrostachya.

The pentacyclic triterpenes rhoiptelenol and rhoiptelenone have been isolated from Sideritis macrostachya. Rhoiptelenone is a new natural compound, whose structure has been determined as D:B-friedo-urs-5-en-3-one. The 1H and 13C NMR spectra of rhoiptelenol, rhoiptelenol acetate and glutinol have been reassigned. The natural occurrence of the D:B-friedo-ursene and D:B-friedo-oleanene derivatives has been examined.

Synthesis of octahydroquinolines through the Lewis acid catalyzed reaction of vinyl allenes and imines.

The reaction of vinyl allenes with imines under Lewis acid catalysis has been explored. Vinyl allenes in which the allenic portion of the molecule is tri- or tetrasubstituted gave octahydroquinoline derivatives as single isomers together with a minor compound formed by an ene reaction of the imine with the allene. Compounds in which the allene is 1,3-disubstituted do not react under the conditions assayed.

Controlled incorporation of water molecules into carboxy hydrogen-bond networks: a designed approach.

The incorporation of water molecules into the hydrogen-bonded pattern of condensed organic materials implies an unfavorable entropic tradeoff resulting from water ordering. Here we show for a family of diacids of general structure (+/-)-1 that extended chains of anhydrous or hydrated structures can be prepared by controlling the steric factors that lead to the closest packing of individual components.

Four new alkaloids from Consolida glandulosa.

The structures of four new hetisine-type diterpenoids, 9-deoxyglanduline (1), glandulosine (2), 11,13-O-diacetylglanduline (3), and 9-O-acetylglanduline (4), isolated from Consolida glandulosa, were determined by two-dimensional NMR techniques. All the structures of these compounds were substantiated by a single-crystal X-ray analysis performed on compound 3.

Novel bis-betaines and betaines within [1(4)]meta-heterophane frameworks.

After prior selection of betaine building blocks for the construction of quadrupolar heterophane frameworks, a convergent "3+1" synthetic strategy is reported for the synthesis of the title macrocycles composed of heterocyclic betaine subunit(s). These typify the first example of simple cyclophanes constructed out of both highly pi-excessive and highly pi-deficient heteroaromatic moieties linked in a 1,3-alternating fashion. The chemical reactivity of the quadrupolar heterophanes 1a and 1c toward electrophiles under neutral conditions corroborated their bis-betaine structure. The structural features of the bis-betaines 1, betaines 2 x PF6 and 5 x X, and the corresponding dicationic [1(4)]heterophanes 3 x 2X and 4 x 2Cl were studied by 1H and 13C NMR spectroscopy and electrospray ionization mass spectrometry, and confirmed by single-crystal X-ray diffraction analysis of macrocycles 1a and 2a x PF6.