Esa T. T. Kumpulainen

Catalytic Activity Dependency on Catalyst Components in Aerobic Copper-TEMPO Oxidation

The influence of catalyst components in the copper-TEMPO (2,2,6,6-tetramethylpiperidine N-oxide) catalysed aerobic oxidation of alcohols was investigated. The type and amount of base greatly influences reactivity. The bipyridyl ligand concentration had no major influence on catalysis, but excessive amounts led to a decrease in activity for longer reaction times. The kinetic dependency for TEMPO was found to be 1.15, and for copper 2.25, which is an indication of a binuclear catalytic system. Optimised conditions with various allylic and aliphatic alcohols give good to excellent rapid oxidations.

Highly Chemoselective Copper-Catalyzed Conjugate Reduction of Stereochemically Labile alpha,beta-Unsaturated Amino Ketones

Highly chemoselective conjugate reduction of chiral alpha,beta-unsaturated amino ketones has been developed by using triisopropyl phosphite ligated copper hydride complex. The highlights of the method are wide substrate compatibility and exceptional chemoselectivity.

Conformational ensembles of flexible beta-turn mimetics in DMSO-d(6)

Beta-turns play an important role in peptide and protein chemistry, biophysics, and bioinformatics. The aim of this research was to study short linear peptides that have a high propensity to form beta-turn structures in solution. In particular, we examined conformational ensembles of beta-turn forming peptides with a general sequence CBz-L-Ala-L-Xaa-Gly-L-Ala-OtBu. These tetrapeptides, APGA, A(4R)MePGA, and A(4S)MePGA, incorporate proline, (4R)-methylproline, and (4S)-methylproline, respectively, at the Xaa position. To determine the influence of the 4-methyl substituted prolines on the beta-turn populations, the NAMFIS (NMR analysis of molecular flexibility in solution) deconvolution analysis for these three peptides were performed in DMSO-d(6) solution. The NBO (natural bond orbital) method was employed to gain further insight into the results obtained from the NAMFIS analysis. The emphasis in the NBO analysis was to characterize remote intramolecular interactions that could influence the backbone-backbone interactions contributing to beta-turn stability. NAMFIS results indicate that the enantiospecific incorporation of the methyl substituent at the C(gamma) (C4) position of the proline residue can be used to selectively control the pyrrolidine ring puckering propensities and, consequently, the preferred varphi,psi angles associated with the proline residue in beta-turn forming peptides. The NAMFIS analyses show that the presence of (4S)-methylproline in A(4S)MePGA considerably increased the type II beta-turn population with respect to APGA and A(4R)MePGA. The NBO calculations suggest that this observation can be rationalized based on an n-->pi* interaction between the N-terminus alanine carbonyl oxygen and the proline carbonyl group. Several other interactions between remote orbitals in these peptides provide a more detailed explanation for the observed population distributions.

C(21)-C(40) of tetrafibricin via metal catalysis: beyond stoichiometric chiral reagents, auxiliaries, and premetalated nucleophiles.

The C(21)-C(40) fragment of fibrinogen receptor inhibitor tetrafibricin was prepared in 12 steps from propane diol (longest linear sequence). In this approach, 6 C-C bonds are formed via asymmetric iridium catalyzed transfer hydrogenative carbonyl allylation and 2 C═C bonds are formed via Grubbs olefin cross-metathesis.