Multistep Cascade Reactions Research Articles

Syntheses of a Novel Class of 5/6/5-Heterocycles: Convenient Routes from Aldehydes to Bis(1,3,4-thiadiazolo)-1,3,5-triazinium Halides

Novel 5/6/5 heterocycles, 1,3,4-thiadiazolo[3,2-a]-1,3,4-thiadiazolo[3,2-d]-1,3,5-triazinium halides 7, have been synthesized by the reaction of 2-amino-1,3,4-thiadiazoles 6 with either 1-(haloalkyl)pyridinium halides 4 or N,N′-methylenebis(pyridinium) dibromides 5. The tricyclic compounds 7 are generated in the course of several successive reaction steps in which specific proton migrations, bond-breaking and bond-forming processes occur. The structures 7 have been verified by spectral data (1H and 13C NMR, MS), X-ray analysis and ab initio calculations. The latter show that both sp2-C atoms C(10) and C(12) of 7 are significantly positively charged and, therefore, exhibit electrophilic properties towards the primary amino group of the amino-thiadiazoles 6. In the course of a multi-step reaction cascade of the 6/7 mixture, novel multi-aza/thia heterocycles 8 are formed. The structures of the latter compounds have been confirmed by X-ray analysis as well as by detailed experimental and theoretical NMR-spectroscopic studies.

Thermal Rearrangements, XXV. The Automerization of Benzene as A Radical‐Initiated Reaction

AbstractThe thermal isomerization of [1,4‐D2]‐ (3a) and [1,2‐13C2]benzene (1a) has been studied in excess hydrogen at 750–850°C with contact time less than 1.2 s and very low partial pressure in a quartz flow system. In both cases, the main isomerization products are the corresponding meta isomers. The data suggest a radical intramolecular interchange of the benzene carbon atoms by 1,2‐C shifts. The multistep reaction cascade is initiated by H addition to the benzene ring followed by transannular homoallyl rearrangements involving the intermediate formation of bicyclo[3.1.0]hexenyl and cyclopentadienylmethyl radicals. This pathway constitutes a side reaction competing with the direct stabilization of the cyclohexadienyl radicals formed preferentially at high temperature.

Odor recognition and second messenger signaling in olfactory receptor neurons

The detection of volatile odorants is supposed to begin with their interaction with soluble binding proteins which shuttle the hydrophobic ligands through the aqueous mucus layer towards specific odorant receptors in the ciliary membrane of olfactory neurons. A large family of receptors for odorants has been identified recently; individual receptor types are expressed in subsets of cells distributed in distinct zones of the olfactory epithelium. Ligand-receptor interaction triggers a rapid multistep reaction cascade, ultimately leading to an electrical response of the receptor neuron. Olfactory signaling is terminated by phosphorylation of receptors via a negative feedback reaction catalyzed by two types of kinases.

Signal recognition and chemoelectrical transduction in olfaction

The mimicking of olfaction is considered to be a promising approach for the construction of artificial odour-sensing systems. In the nose, the detection of volatile odorants begins when the odorant ligands interact with specific odorant receptors in the ciliary membrane of the olfactory neurons. A large family of genes encoding putative odorant receptors has been identified recently. Individual receptor types are expressed in subsets of cells distributed in distinct zones of the olfactory epithelium. Ligand-receptor interaction triggers a rapid multistep reaction cascade, resulting in a “pulse” of second messengers that initiates an electrical response from the receptor neuron. Olfactory signalling is terminated by phosphorylation of receptors via a negative feedback reaction, catalyzed by specific kinases.

Rapid kinetics of second messenger formation in olfactory transduction

Olfactory transduction is thought to be mediated by a membrane-bound receptor protein initiating a multistep reaction cascade which ultimately leads to a depolarizing generator current. There is considerable evidence for the involvement of adenylate cyclase in vertebrate olfactory transduction, and some data indicate that phospholipase C may have a central role in insect olfaction. However, one must show that odorants not only stimulate enzyme activity but also induce changes in concentrations of relevant second messengers. One important criterion for a candidate second messenger of chemo-electrical transduction is that its formation must precede the onset of the odorant-induced membrane permeability changes which proceed on a subsecond time-scale. Here we report an odorant-induced, transient accumulation of cyclic AMP in isolated olfactory cilia from rats, and the generation of inositol trisphosphate in antennal preparations from insects, both of which show subsecond time courses that are sufficiently rapid to mediate the odorant-regulated permeability of olfactory receptor cells.