piperidines and sedridine

The catalytic asymmetric aminoallylation of chiral aldehydes is developed as a new method for the catalyst controlled synthesis of syn- and anti-1,3-aminoalcohols. This methodology is highlighted in the synthesis of the sedum alkaloids (+)-sedridine and (+)-allosedridine both of which have their final carbon incorporated during closure of the piperidine ring via a hydroformylation with formaldehyde.

Topics: Alkaloids; Amino Alcohols; Catalysis; Formaldehyde; Piperidines; Sedum; Stereoisomerism

An efficient total synthesis of the natural alkaloid (+)-dumetorine by using flow technology is described. The process entailed five separate steps starting from the enantiopure (S)-2-(piperidin-2-yl)ethanol 4 with 29% overall yield. Most of the reactions were carried out by exploiting solvent superheating and by using packed columns of immobilized reagents or scavengers to minimize handling. New protocols for performing classical reactions under continuous flow are disclosed: the ring-closing metathesis reaction with a novel polyethylene glycol-supported Hoveyda catalyst and the unprecedented flow deprotection/Eschweiler-Clarke methylation sequence. The new protocols developed for the synthesis of (+)-dumetorine were applied to the synthesis of its simplified natural congeners (-)-sedamine and (+)-sedridine.

Topics: Alkaloids; Catalysis; Cyclization; Molecular Structure; Piperidines; Solvents; Stereoisomerism; Technology; Temperature

[reaction: see text] N-Sulfinyl beta-amino Weinreb amides are prepared by condensation of sulfinimines with the potassium enolate of N-methoxy-N-methylacetamide. These new chiral building blocks are useful for the asymmetric synthesis of beta-amino carbonyl compounds, as illustrated here by the concise enantioselective syntheses of sedum alkaloids (+)-sedridine and (-)-allosedridine.

Topics: Amides; Indicators and Reagents; Magnetic Resonance Spectroscopy; Piperidines; Stereoisomerism; Sulfoxides

Kinetic resolution of N-Boc-piperidine-2-ethanol (2), a case of remote stereocenter discrimination, was accomplished by sequential transesterification mediated by two enzymes, Lipase PS and porcine pancreatic lipase, showing opposite enantioselectivity. The gram-scale availability of the two enantiomeric N-Boc alcohols 2a (R) and 2c (S) enlarges their synthetic exploitation for the enantioselective preparation of piperidine alkaloids. As an example, the convenient three-step synthesis of both the enantiomers of sedamine and allosedamine is described.

Topics: Acetylation; Alkaloids; Animals; Kinetics; Lipase; Models, Chemical; Molecular Structure; Piperidines; Stereoisomerism

Topics: Alkaloids; Chemistry, Pharmaceutical; Pharmacology; Pharmacy; Piperidines; Pyridines; Research