The SAMP-/RAMP-hydrazone methodology in asymmetric synthesis

This paper is concerned with the nature of the chiral inducer in the high pressure-induced conjugate addition of amines to auxiliary-tethered crotonates. Almost complete stereocontrol was obtained in the addition of diphenylmethanamine to crotonates derived from the “arylmenthol” auxiliaries 18a, 18c, and 4 bearing an o-methoxyphenyl, p-phenoxyphenyl, or β-naphthyl substituent, respectively. This high efficiency has been attributed to the predominance of stacked conformations in such crotonates, a hypothesis supported by the 1H NMR spectra, calculated energy of conformational optima of the corresponding crotonates, and X-ray crystal structure of 5a. The arene and enoate appendages are roughly coplanar, separated by 3.4−4 A. In contrast, only moderate selectivities could be achieved using various trans-2-arylcyclohexanols (27, 28, 2c, 29) as auxiliaries. In these cases the efficiency appears to be seriously compromised by the “widening V” arrangement exhibited by the two π-systems, as shown in the X-ray cr...

Investigating the π-Facial Discrimination Phenomenon in the Conjugate Addition of Amines to Chiral Crotonates: A Convenient Basis for the Rational Design of Chiral Auxiliaries

Diastereoselectivity in the intermolecular Pauson-Khand reaction of chiral 2-alkynoates

Human immunodeficiency virus 1 integrase (HIV-1 IN) is the enzyme responsible for integrating the viral DNA into the host genome, and is essential to the replication of the virus. L-Chicoric acid (L-CA) is a bidentate catechol that has been identified as a potent inhibitor of HIV-1 IN. Using the new Autodock 4.0 free-energy function we have obtained a L-CA binding mode that explains its observed potency and is consistent with available experimental data. Because of the alpha,beta-unsaturated ester functionality of the side arms of L-CA we first performed an extensive conformational analysis of L-CA using semiempirical and ab initio calculations. As a result we have identified two distinct L-CA binding modes, one for the s-cis/s-cis and another for the s-cis/s-trans isomers. The most stable conformer was found to be the structure with the alpha,beta-unsaturated ester in the s-cis conformation for both arms of L-CA. This conformer also gave the top-ranked docking solution. Analysis of the interactions with key IN residues, combined with results using a L-CA tetraacetylated derivative and a Q148A IN mutant, correlate well with the experimental data.

A docking study of L-chicoric acid with HIV-1 integrase.

Enantioselective conjugate additions of silylketene acetals to 2-carboxycyclopentenones promoted by chiral Ti complexes

The s-cis/s-trans preference of acyclic α,β-unsaturated esters has been studied by their reactions to elucidate the preference in the transition state and by supersonic jet spectroscopy, NOE experiments, and X-ray analysis to clarify the preference in the ground state. It has been rudely accepted that enoate-Lewis acid complexes prefer the s-trans conformation not only in the ground state but also in the transition state of the reactions involving those complexes. The conjugate addition of metal amides to uncomplexed enoates proceeds predominantly through the s-cis conformation, and most organocopper conjugate additions in the absence of Lewis acids or related metal salts take place preferentially in the s-cis conformation

Taeko Niwa

Papers

Studies on s-Cis/s-Trans Preference of Acyclic .alpha.,.beta.-Unsaturated Esters. Reactions, Supersonic Jet Spectroscopy, NOEs, and X-ray Analysis