Piperidine ring synthesi

In spite of the diverse nature of alkaloid structures, two structural units, i.e. fused pyrrolidine and piperidine rings in different oxidation states, appear as rather common denominators. We therefore chose to give several examples for four types of synthetic reactions which have frequently been used in alkaloid total synthesis and which provide generally useful routes to polycyclic compounds with five- or six-membered rings containing one nitrogen atom. These are ... 

Reduction of the exocylic double bond and inclusion of the side chain nitrogen in a piperidine ring leads to a compound (19) which exhibits skeletal muscle relaxant activity. Its one step synthesis begins with reaction of thioxanthene (17) with phenyl sodium... 

Other routes to piperidines involving 1,4-addition reactions include the incorporation of a Michael addition reaction as the piperidine ring formation step in the total synthesis of Histrionicotoxin <06JA12656> and the use of an intramolecular 1,4-addition, 6-endo-dig ring... 

The resulting derivatives (269) can be considered as strategically important intermediates in the synthesis of glycosidase inhibitors and carbocyclic nucleosides (150). A new approach to the stereoselective synthesis of the piperidine ring with the use of [4+ 2] [3+ 2]-cycloaddition from specially prepared substrates is also very interesting (431)b, c. In the context of this problem, the conditions for the formation of systems containing quaternary vicinal stereocenters were found. 

If the synthesis is carried out without ammonia the six-ring synthesis of Knoevenagel takes place. This synthesis, which is catalytically induced by bases such as diethylamine and piperidine, consists in ring closure of the intermediate product, of which the di-enol form is shown above. 

Sufentanyl Sufentanyl, iV-(4-(methoxymethyl)-l-[2-(2-thienyl)ethyl]-iV-phenylpropanamide (3.1.72), is a drag that is analogous to alfentanil, but that differs by the substituent on the nitrogen atom of the piperidine ring. Its synthesis contains many of the same elements as the synthesis of alfentanil, and it only differs in the last stage, where alkylation of 4-methoxymethyl-4-iV-propionilanihnopiperidine (3.1.68) is carried out with 2-hydroxy-ethylthiophofene methanesulfonate [44-46]. 

The chiral center on the piperidine ring retained stereochemical integrity to this point in the synthesis, and provided the basis for a relatively modest level (72 28 threo erythro) of substrate-based stereocontrol in the BH3-THF/H202 hydroboration/oxidation of the... 

The rare reports of quinolizidine formation by a nitrone cycloaddition strategy include the racemic total synthesis of lasubine II (58), one of a series of related alkaloid isolated from the leaves of Lagerstoemia subcostata Koehne (Scheme 1.14) (104). While these alkaloids were previously accessed by infennolecular nitrone cycloaddition reactions, this more recent report uses an intramolecular approach to form the desired piperidine ring. Thus, cycloaddition of nitrone 59 affords predominantly the desired bridged adduct 60 along with two related... 

A short total synthesis of (-l-)-prosopinine 36 from (R)-serine was achieved via cyclohydrocarbonylation catalyzed by Rh-BIPHEPHOS complex for the construction of the key piperidine ring (2R,33 )-33 (Scheme 6). Compound 33 was converted to (-l-)-prosopinine 36 via the nucleophilic displacement of the ethoxy group with organocopper reagent 34 forming 35, followed by deprotection. A similar procedure has been used for the total synthesis of (—)-deoxoprosophylline 37. 

Piperidine ring-expansion methodology and aziridinium ion intermediate formation has been demonstrated to provide good regio- and stereochemical control in the synthesis of substituted azepanes. Reaction of 298 with azide ion afforded 300 from preferential attack from behind by the azide ion at the methine carbon in the intermediate 299 (Scheme 38) <2002J(P1)2080>. 

Scheme 21. Synthesis of 2,3,5,6-tetrasubstituted piperidine ring system 64...

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