Claisen rearrangement

About: Claisen rearrangement is a research topic. Over the lifetime, 3783 publications have been published within this topic receiving 57974 citations.

First Asymmetric Total Synthesis of Tetrodotoxin

Abstract: Tetrodotoxin, a toxic principle of puffer fish poisoning, is one of the most famous marine natural products because of the complex structure having many functional groups and its potent biological activity leading to death. Since the structure elucidation in 1964, this toxin has been recognized as a formidable target molecule for total synthesis. We have recently achieved the first asymmetric total synthesis from 2-acetoxy-tri-O-acetyl-d-glucal as a chiral starting material. The highly hydroxylated cyclohexane ring was constructed by Claisen rearrangement and regioselective hydroxylations of an acetone moiety and an intramolecular directed aldol condensation of the precursor having methyl ketone with dihydroxyacetone, which was synthesized through Sonogashira coupling. Installation of nitrogen functionality was unsuccessful through an attempted Overman rearrangement. We, therefore, employed a new intramolecular conjugate addition strategy between the carbamate and unsaturated ester groups. The alpha-hydroxyl lactone moiety was synthesized through an intramolecular epoxide opening by the Z-enolate of aldehyde, which was followed by oxidation-reduction of the resulting cyclic vinyl ether. The lactone was then converted to a protected ortho ester, and then gunanidinylation was followed by cleavage of the 1,2-glycol to give the fully protected tetrodotoxin. Selection of the protective groups has finally led us to accomplish the total synthesis of tetrodotoxin in an enantiomerically pure form. All the stereogenic centers were controlled with high selectivity, and the hydroxyl groups were differently protected to discriminate for the future analogue synthesis of a bioorganic program. The synthetic tetrodotoxin was purified by ion exchange chromatography and characterized to be identical with the natural compound.

The near attack conformation approach to the study of the chorismate to prephenate reaction.

Abstract: Standard free energies (ΔGN°) for formation of near attack conformers, those ground state conformers that can convert directly to the transition state, were calculated for the Claisen rearrangement of chorismate to prephenate in six different environments: water, wild-type enzymes from Bacillus subtilis and Escherichia coli, their Arg90Cit and Glu52Ala mutants, and the 1F7 catalytic antibody. Values of the calculated ΔGN°s and the experimentally determined activation energies (ΔG‡) are linearly related with the slope of ≈1. This demonstrates that the relative rate of the chorismate → prephenate reaction is overwhelmingly dependent on the efficiency of formation of near attack conformers in the ground state.

Total Synthesis of (±)-Garsubellin A

Abstract: The first total synthesis of garsubellin A, a neurotrophic compound with potent choline acetyltransferase-inducing activity, is described. Keys for success were (1) stereoselective intermolecular aldol reaction at the C-4 position with acetaldehyde, (2) stereoelective Claisen rearrangement to introduce an allyl group to the most sterically crowded position at C-6, (3) ring-closing metathesis to construct the B-ring, and (4) Wacker-type oxidative C-ring formation. This synthetic route can be extended to an asymmetric synthesis of garsubellin A using the Koga catalytic enantioselective alkylation, which produced enantioenriched alpha-prenyl cyclohexenone with excellent enantioselectivity (95% ee).

Synthesis and Claisen rearrangement of alkoxyallyl enol ethers. Evidence for a dipolar transition state

Abstract: Etude de l'effet d'un substituant alcoxy sur le groupe allyl d'(allyl vinyl) ethers sur la vitesse de transposition Claisen de ces ethers