Molecules as Biotic Messengers.

Chemical ecology has grown as a scientific discipline from its earliest days of tracking the exquisitely potent chemistry of insect pheromones to a deep understanding of the molecular, physiological, and behavioral interactions governed by naturally occurring small molecules. The current practice of the field relies on knowledge of genomes and gene expression patterns, protein biology, and small-molecule chemistry, providing illustrations of ecological and evolutionary patterns in natural communities.

Sequestered defensive toxins in tetrapod vertebrates: principles, patterns, and prospects for future studies.

Chemical defenses are widespread among animals, and the compounds involved may be either synthesized from nontoxic precursors or sequestered from an environmental source. Defensive sequestration has been studied extensively among invertebrates, but relatively few examples have been documented among vertebrates. Nonetheless, the number of described cases of defensive sequestration in tetrapod vertebrates has increased recently and includes diverse lineages of amphibians and reptiles (including birds).

2D NMR-spectroscopic screening reveals polyketides in ladybugs.

Small molecules of biological origin continue to yield the most promising leads for drug design, but systematic approaches for exploring nature's cache of structural diversity are lacking. Here, we demonstrate the use of 2D NMR spectroscopy to screen a library of biorationally selected insect metabolite samples for partial structures indicating the presence of new chemical entities. This NMR-spectroscopic survey enabled detection of novel compounds in complex metabolite mixtures without prior fractionation or isolation.

Natural products as molecular messengers.

The chemistry of naturally occurring compounds has long been pursued in the search for medicines, dyes, pesticides, flavors, and fragrances. In addition, the deeper aim of understanding life itself as a chemical phenomenon has motivated generations of scientists. One consequence of such studies has been the realization that natural products often serve central roles as biological signaling agents.

NMR-spectroscopic screening of spider venom reveals sulfated nucleosides as major components for the brown recluse and related species.

Extensive chemical analyses of spider venoms from many species have revealed complex mixtures of biologically active compounds, of which several have provided important leads for drug development. We have recently shown that NMR spectroscopy can be used advantageously for a direct structural characterization of the small-molecule content of such complex mixtures. Here, we report the application of this strategy to a larger-scale analysis of a collection of spider venoms representing >70 species, which, in combination with mass spectrometric analyses, allowed the identification of a wide range of known, and several previously undescribed, small molecules.

Defensive Chemistry of Lycid Beetles and of Mimetic Cerambycid Beetles that Feed on Them.

Beetles of the family Lycidae have long been known to be chemically protected. We present evidence that North American species of the lycid genera Calopteron and Lycus are rejected by thrushes, wolf spiders, and orb-weaving spiders, and that they contain a systemic compound that could account, at least in part, for this unacceptability. This compound, a novel acetylenic acid that we named lycidic acid, proved actively deterrent in feeding tests with wolf spiders and coccinellid beetles.

Grass roots chemistry: meta-tyrosine, an herbicidal nonprotein amino acid.

Fine fescue grasses displace neighboring plants by depositing large quantities of an aqueous phytotoxic root exudate in the soil rhizosphere. Via activity-guided fractionation, we have isolated and identified the nonprotein amino acid m-tyrosine as the major active component. m-Tyrosine is significantly more phytotoxic than its structural isomers o- and p-tyrosine.

Dietary sequestration of defensive steroids in nuchal glands of the Asian snake Rhabdophis tigrinus.

The Asian snake Rhabdophis tigrinus possesses specialized defensive glands on its neck that contain steroidal toxins known as bufadienolides. We hypothesized that R. tigrinus does not synthesize these defensive steroids but instead sequesters the toxins from toads it consumes as prey.

Pinoresinol: A lignol of plant origin serving for defense in a caterpillar.

Pinoresinol, a lignan of wide distribution in plants, is found to occur as a minor component in the defensive secretion produced by glandular hairs of caterpillars of the cabbage butterfly, Pieris rapae. The compound or a derivative is appropriated by the larva from its normal food plant (the cabbage, Brassica oleracea). Pinoresinol was shown to be absent from the secretion if the larva was given a cabbage-free diet but present in the effluent if that diet was supplemented with pinoresinol.

Exploring uncharted terrain in nature's structure space using capillary NMR spectroscopy: 13 steroids from 50 fireflies.

Capillary NMR spectroscopy (CapNMR) was used to characterize 13 new cardenolides and related steroids from a severely mass-limited natural products sample derived from a rare firefly, Lucidota atra. These analyses were carried out on only partially purified samples, each containing 20-100 mug of up to three steroids. Compared to other NMR spectroscopic techniques, CapNMR provided an up to 3-fold gain in sensitivity while maintaining very high spectral quality, which was essential for the identification of the L.

Location of double bonds in diene and triene acetates by partial reduction followed by methylthiolation.

Two random reduction procedures (NH2NH2/H2O2 and NH2NH2/O2) were compared and conditions optimized for the reduction of two synthetic pheromone compounds (9Z,11E)-9,11-tetradecadienyl acetate and (9Z,12E)-9,12-tetradecadienyl acetate on a 300 microg scale at 60 degrees C. The relative amounts of the four products (completely reduced acetate, unreacted diene acetate and two monoene acetates), characterized by gas chromatography (GC) from the reaction mixture, depended on the reaction conditions. The reduction was straightforward without any detectable undesired side products.

Personal reflections on receiving the Roger Adams Award in organic chemistry.

The author reflects on his early experiences as a chemist, and on the subsequent shift in emphasis that his research has undergone from mechanistic and synthetic organic chemistry to natural products chemistry. Finally, the extension of the field of natural products chemistry into the emerging discipline of chemical ecology is noted. This essay concludes with a consideration of the importance of including science in the curricula of all college and university students.

Study of the interaction of chlorisondamine and chlorisondamine analogues with an epitope of the alpha-2 neuronal acetylcholine nicotinic receptor subunit.

Chlorisondamine (CHL), a neuronal nicotinic ganglionic blocker, when injected in the cerebral ventricle of rats chronically blocks the increase in locomotion and rearing by subcutaneous nicotine injection. The blocking of the ion channel(s) prevents nicotine from exerting its rewarding effects on the CNS. When administered intraperitoneally, a dose 400-500 times the intracerebroventricular one is needed to cross the blood-brain barrier and to generate the same level of nicotine antagonism, resulting in severe side-effects, thus making it unlikely to be used as a therapeutical compound.

Chiral silylation reagents: determining configuration via NMR-spectroscopic coanalysis.

[structure: see text]Derivatization with (+)- and (-)-chloromenthoxydiphenylsilane was used to determine the absolute configuration of the insect defensive agent pinoresinol (1). Although the (1)H NMR chemical shift differences of the resulting two diastereomers are small, (1)H NMR spectroscopy provided for the unambiguous assignment of the natural product's configuration. For this purpose, a new approach involving NMR spectra of mixtures of diastereomers was used.

A new approach to natural products discovery exemplified by the identification of sulfated nucleosides in spider venom.

Using a new approach based on the NMR spectroscopic analysis of the entire, unpurified spider venom, we identified a family of unusual sulfated nucleoside derivatives from the venom of the hobo spider, Tegenaria agrestis. These compounds are ribonucleoside mono- and disulfates derived from guanosine and xanthosine, some of which are glycosylated, bearing one or two D-fucose units. The use of NMR spectroscopy to characterize the unfractionated venom was central to the discovery of this heretofore overlooked class of venom components.

Defensive chemicals of two species of Trachypachus Motschulski.

Analyses of pygidial gland contents of two species of a previously uninvestigated family of beetles (Trachypachidae) by Gas Chromatography-Mass Spectrometry (GC-MS) revealed that their chemistry is similar to that reported from many members of the family Carabidae. Nevertheless, the composition of defensive gland fluids of the two species Trachypachus slevini and T. gibbsii differs sufficiently to distinguish between the two species solely on the basis of their defensive chemistry.

New non-glycosidic diterpenes from the leaves of Stevia rebaudiana.

Six new labdane-type, non-glycosidic diterpenes, sterebins I-N (1-6), were isolated from the leaves of Stevia rebaudiana. Their structures, analogous to those of the previously described sterebins A-H, were elucidated on the basis of spectroscopic and chemical studies.

New silyl ether reagents for the absolute stereochemical determination of secondary alcohols.

[reaction: see text] Herein we report a new set of silyl ether reagents for determining the enantiomeric purity and absolute stereochemistry of secondary alcohols. These derivatives are easily synthesized, provide straightforward spectroscopic results, and allow for facile recovery of the original chiral alcohol.

Synthesis of mayolene-16 and mayolene-18: larval defensive lipids from the European cabbage butterfly.

A tandem Wittig approach has been employed for the synthesis of both (11S,9Z,12Z,15Z)- and (11R,9Z,12Z,15Z)-hydroxyoctadeca-9,12,15-trienoic acid (11-hydroxylinolenic acid, 11-HLA) from (R)-glyceraldehyde acetonide. From (11R)-HLA we have prepared the corresponding palmitic acid and stearic acid esters, mayolene-16 (1) and mayolene-18 (2), insect defensive compounds recently identified from Pieris rapae larvae. In addition, we describe the synthesis of three macrocyclic oligomers (24-26) derived from (11R)-HLA.