Tetrahydropyridines peroxidation

A5. Adams, J. D., Odunze, I. N., and Sevanian, A., Induction by l-methyl-4-phenyl-l,2,3, 6-tetrahydropyridine of lipid peroxidation in vivo in vitamin E deficient mice. Biochem. Pharmacol. 39, R5-R8 (1990). 

A regioselective free radical initiated reaction between 1,2,5,6-tetrahydropyridine and thiiranes has been shown to produce /3-aminothiols (311), which cyclize on boiling under reflux with di-/-butyl peroxide in chlorobenzene to give perhydrothiazolo[3,2-a]pyridine derivatives (312) (82TL5039). 

The importance of fully or partially hydrogenated isoxazolo[2,3-a]pyridines as intermediates in the synthesis of stereochemically complex molecules, particularly alkaloids, has led to a continued high level of interest in their preparation. The route of choice remains the 1,3-dipolar cycloaddition reaction between a tetrahydropyridine A-oxide, that is a nitrone, and a dipolarophile. A number of methods for the production of the nitrone for in situ reaction have been developed. They include the oxidation of the secondary amine, piperidine, with hydrogen peroxide in the presence of... 

The 1,2-dihydropyridine chromium tricarbonyl complex (85) has been converted into the tetrahydropyridine (86) as shown in Scheme 32. The endo peroxides of l-alkoxycarbonyl-l,2-dihydropyridines, e.g. (87) react with carbon nucleophiles such as enamines, in the presence of stannous chloride, to give substitution products, e.g. (88) (Scheme 33). ... 

Studies on A -methyl,4-phenyl-l,2,3,6 tetrahydropyridine (MPTP)-induced model of PD indicate that activities of PLA2, COX-2, and rate of lipid peroxidation are increased (Table 8.3), and PLA2, COX inhibitors, and some antioxidants protect neural cells from MPTP-mediated neurodegeneration (Yoshinaga et al., 2000 Teismann et al., 2003 Farooqui et al., 2006). Similarly, arachidonic acid signaling is upregulated in the caudate-putamen and frontal cortex of unilaterally... 

An interesting synthesis of 5-amino-5-deoxy-DL-piperidinoses from l-acyl-1,2-dihydro-pyridines (21) has been reported (Scheme 2). The photochemical oxidation of (21) afforded the bicyclic peroxide (22) which on reduction gave the tetrahydropyridine (23). Hydroxylation of (23) afforded the cyanohydrin (24), which on hydrolysis and reduction afforded the methyl piperidinoses (25)-(27). (See also Vol. 12, p. 71.)... 

Methyl - 4 - phenyl -1,2,3,6 - tetrahydropyridine (MPTP) is a frequently used animal model for Parkinson s disease. When injected into animals, MPTP is taken up by the cells in the substantia nigra where monoamino oxidase B (EC 1.4.3.4) converts it to l-methyl-4-phenylpyridinium ion (MPP ). This ion induces free radicals and duplicates many of the signs of Parkinson s disease in animals. In mice melatonin attenuated the resulting damage in the central nervous system (Acuna-Castroviejo et al. 1997). MPTP-induced neural lipid peroxidation was reduced to control levels when melatonin was co-administered with the herbicide. Neuronal loss and MPTP-induced reduction of tyrosine hydroxylase (EC 1.14.16.2) activity in neurones of the striatum were attenuated by melatonin. 

---