Determination of the absolute structure of (+)-akaterpin

We describe the total synthesis and structural determination of (+)-akaterpin (1), an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC). The key features of the synthetic strategy include the resolution of β,γ-unsaturated ketone (±)-2a with chiral sulfoximine 6. The absolute stereochemistry was determined by comparison of the specific optical rotation data of (+)-1 and (-)-1 with that of natural akaterpin.     

General entry to asymmetric one-pot [N + 2 + N] cyclization for the synthesis of three- to seven-membered azacycloalkanes

Enantio- and diastereoselective one-pot synthesis of three- to seven-membered cis-azaheterocycles was achieved using a triggered asymmetric conjugate addition reaction of lithium amide with an enoate, followed by alkylation of the resulting lithium enolate with α,ω-dihaloalkane and N-alkylation. Isomerization of cis-azaheterocycles with a base yielded the trans-product, constituting a one-pot synthesis of cis-azacycles and a two-step synthesis of trans-azacycles. The four-step asymmetric synthesis of nemonapride highlights the general utility of the method.     

13C Chemical shifts and conformational equilibria in quaternary piperidinium salts

Carbon-13 nuclear magnetic resonance spectra of a series of N-methyl-N-alkylpiperidinium salts have been measured, and the observed chemical shifts analysed in terms of the stereochemical and conformational properties of the molecules. Furthermore, the differences of the free energy (ΔG°) between two conformers on ring inversion have been estimated.