Piperidine bases

Aminolysis of 0-aryloximes shows a third-order term for both pyrrolidine and piperidine bases temperature effects on different routes are reported and explained. Hydrolysis of a-hydroxy-a-phenylbenzeneacetic acid salicylidenehydrazide (33) in aqueous ethanol proceeds via fast protonation, followed by rate-determining attack of water the results are compared with several related molecules. 

Yet another piperidine-based antipsychotic agent replaces the butyrophenone or diarylpropyl function found in earlier compounds by a benzopyrimidine group. The synthesis starts by the conversion of the carboxylic acid in piperidine (22-1) to its acid chloride. Reaction with 1,3-difluorobenzene (22-2) in the presence of aluminum chloride affords the acylated product (22-3). Reaction with hydroxylamine leads to the corresponding oxime (22-4). Treatment of that derivative with a base... 

Stereoselective total syntheses of (-)-deoxoprosopinine (20) and (-)-deoxoprosophylline (21), derived respectively from the natural bases prosopinine and prosophylline, have been described the route adopted should be applicable to other related piperidine bases.20 Prosafrinine (22), a piperidine alkaloid of Prosopis africana, has been synthesized stereoselectively, along with pseudocar-pamic acid (23), as racemic varieties.21 Additional stereoselective syntheses of ( )-carpamic and ( )-azimic acids have been described.22... 

Donor-n-acceptor dyads can be employed as molecular rectifiers. For this purpose, a quinolinium hemicyanine was prepared by Ashwell et al. [14], Reaction between 33 and 34 in the presence of piperidine base gave the dyad 35 (Scheme 10.10). 

Most amphibian alkaloids are not as complex in structure as the steroidal batrachotoxins and samandarines. Of the 300 known amphibian alkaloids, most have been characterized from the skin extracts of frogs of the family Dendrobatidae and, hence, have been referred to as dendrobatid alkaloids. The major bicyclic classes of dendrobatid alkaloids are the histrionicotox-ins, decahydroquinolines, and pumiliotoxin-A class. Because of the presence of a piperidine ring in most dendrobatid alkaloids, they also have been referred to as piperidine-based alkaloids. 

Wasserman et al. utilized an intramolecular imine-epoxide ring opening/cyclization process <88TL4973> to synthesize heterotropanes and substituted piperidines (Scheme 20). This methodology has been applied to the total syntheses of piperidine-based alkaloids (+)-teneraic acid <89TL6077> and ( )-solenopsin-A <88TL4977>. 

Freifelder el al. found rhodium on carbon to be better suited than rhodium on alumina for reduction of the pyridine ring. The poisoning effect of the piperidine base formed can be overcome by use of sufficient catalyst. 

Moll3 gas chromatographed some Conium alkaloids and a number of other piperidine bases. 

Pyridine and piperidine bases occur widely in Nature, both as alkaloids in plants and in the defence secretions of certain insects and amphibians. They frequently co-occur with tetrahydroquinolines and quinolizines with which they share common biosynthetic origins. 

Wu, W. L., Burnett, D. A., Spring, R., Qiang, L., Sasikumar, T. K., Domalski, M. S., Greenlee, W. J., O Neill, K., Hawes, B. E. Synthesis and structure-activity relationships of piperidine-based melanin-concentrating hormone receptor 1 antagonists. Bioorg. Med. Chem. Lett. 2006, 76(14), 3668-3673. 

Piperidine-based dimer ligands were prepared and eval-ed " for their inhibiting activity for dopamine (DA) and atonin (5-HT) transporters (Figure 18.6). Two trans-piperidine units were linked by a pentamethylene spacer to... 

Human renin X-ray anaiysis of a weak, non-peptide, piperidine-based HTS hit (26 pM) reveaied a radicaiiy novel mode of binding associated with a iarge conformationai change of the enzyme that had never been observed before. Structure-guided optimization ied to a low nanomolar, drug-like inhibitor. 189... 

Piperidine-based aminoketones similar to 456 also featured in syntheses of (+ )-427 by Munchhof and Meyers (Scheme 57) 412), and by Solladie and Chu (Scheme 58) 413). In the former, the enantiomerically pure bicyclic oxazolidine-thione 457 underwent Eschenmoser sulfide contraction under forcing conditions to produce the vinylogous urethane 458, which was simultaneously hydrogenated and hydrogenolyzed over Pearlman s catalyst to give the 2,6-c/s-disubstituted piperidine... 

Analogous condensation 203 with dione 217 in ethanol in the presence of piperidine base afforded a mixture of polyannulated bisnaphthyridines 218-220 in a total yield of 82% (1992JCS(P1)1747). 

When pyridine is reduced catalytically in the form of a salt or in acid solution, uptake of hydrogen proceeds rapidly in contrast to its reduction as base in a neutral solvent (10). This falls in line with Maxted s concept of the toxic or unshielded nitrogen atom in both pyridine and piperidine bases and the nontoxic or shielded salt form (30). Calculation of the... 

There are disadvantages in carrying out the hydrogenation of pyridines as salts. When the corresponding piperidine bases are desired, isolation of some of them in good yield is difficult because of their extreme water solubility. The isolation of pure piperidinecarboxylic and piperidine-alkanoic acids after reduction as hydrochloride salts is troublesome and often extremely difficult. The reduction of the corresponding pyridine acids now no longer requires the presence of an acid. This will be discussed in a subsequent section. 

A final point arises from the fact that the stereochemistry at C-2 is not the same in different piperidine bases. For example ( —)-sedamine (20) is 2S whereas (— )-pelletierine [as (23)] is 2R. This indicates that addition of the side chain to A -piperideine (30) can occur on both the re and si faces of the molecule, for later epimerization at C-2 seems to be excluded by tritium retention at this site. 

Kozikowski, A.P., Araldi, G.L., Boja, J., Meil, W.M., Johnson, K.M. et al. (1998) Chemistry and pharmacology of the piperidine-based analogues of cocaine. Identification of potent DA-T inhibitors lacking the tropane skeleton. J. Med. Chem. 41 1962-1969. 

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