Tetsuya Sengoku

A Synthetic Approach to Diverse 3-Acyltetramic Acids via O- to C-Acyl Rearrangement and Application to the Total Synthesis of Penicillenol Series

For the efficient approach to medicinally important α-branched 3-acyltetramic acids, the key reaction of O- to C- acyl rearrangement using α-amino-acid-derived 4-O-acyltetramic acids was extensively examined in the presence of various metal salts. Use of CaCl(2) or NaI dramatically changed the results in the reaction efficiency and rapidly brought about the desired α-branched 3-acyltetramic acids in markedly improved yields. We also discuss an epimerization at C5 stereocenter under the rearrangement conditions as well as the tolerance for structural variation at C3 and C5. In addition to the preceding success in the total synthesis of new cytotoxic tetramic acid, penicillenol A(1), this methodology could be also applied to the first total synthesis of penicillenol A(2).

Catalytic Enantioselective Amide Allylation of Isatins and Its Application in the Synthesis of 2-Oxindole Derivatives Spiro-Fused to the α-Methylene-γ-Butyrolactone Functionality

This article is a full account of the work exploring the potential utility of catalytic enantioselective amide allylation of various isatins using indium-based chiral catalysts. A survey of various isatin substrates and NH-containing stannylated reagents revealed that the reaction has a remarkably wide scope to result in extremely high yields and enantioselectivities (up to >99 %, 99 % ee) of variously substituted homoallylic alcohols. Several mechanistic investigations demonstrated that the substrate-reagent hydrogen-bond interaction plays a critical role in the formation of the key transition states to result in enhanced catalytic reaction. The success of this approach allowed convenient access to chiral 2-oxindoles spiro-fused to the α-methylene-γ-butyrolactone functionality and their halogenated derivatives in almost enantiopure forms, thus highlighting the general utility of this synthetic method to deliver a large variety of antineoplastic drug candidates and pharmaceutically meaningful compounds.

Construction of Spiro-Fused 2-Oxindole/α-Methylene- γ-Butyrolactone Systems with Extremely High Enantioselectivity via Indium-Catalyzed Amide Allylation of N-Methyl Isatin

A remarkably effective method allowing an extremely high enantioselective synthesis of the spiro-fused 2-oxindole/α-methylene-γ-butyrolactones is described. The key strategy lies in the use of indium-catalyzed asymmetric amide allylation of N-methyl isatin with functionalized allylstannanes, which can lead to the antineoplastic spirocyclic lactones in almost enantiopure forms.

First total synthesis of epicoccarine A via O- to C-acyl rearrangement strategy.

The first total synthesis of antibacterial epicoccarine A isolated from a fungus Epicoccum sp. has been accomplished in 10 steps along with synthetic elaboration of its C5-epimer, highlighting the utility of O- to C-acyl rearrangement of a 4-O-acyltetramic acid derivative. Comparison of spectroscopic properties and specific optical rotations of the synthetic samples with those reported for authentic material has clearly indicated the unspecified absolute stereochemistry of this natural product to be 5S.

Mechanistic investigation of energy transfer in perylene-cored anthracene dendrimers

In this publication, we describe results of investigations focusing on detailed mechanisms of directed energy transfer in perylene-cored anthracene dendrimers. To obtain definitive statistical data for probing the energy transfer pathways, we synthesized four analogous dendrimers, which were designed to funnel the energy only from remote anthracene groups to the perylene cores. Static fluorescence studies with these dendrimers revealed that excitation of the anthracene groups led to the core emissions, indicating efficient energy transfer should be involved. Inspection of the energy transfer efficiencies obtained from all ten dendrimers demonstrated that single-step energy transfer should represent a key mechanism for the long-range energy transport in these dendrimers.

Indium-Catalyzed Amide Allylation of N-Carbonyl Imides: Formation of Azaspiro-γ-lactones via Ring Opening–Reclosure

A novel and facile synthesis of azaspiro-γ-lactones with a methylene-lactam framework from N-carbonyl imides is described. Mechanistic investigations provide evidence for a two-step reaction process involving ZnCl(2)-promoted addition of β-amido allylindium species followed by an unexpectedly molecular-sieves-mediated ring opening-reclosure concomitantly with the loss of an N-carbonyl unit.

Spontaneous formation of dye-functionalized gold nanoparticles using reverse micellar systems

Detailed exploratory and mechanistic investigations on spontaneous formation of dye-functionalized gold nanoparticles (GNPs) using dye-based reverse micellar systems are described in this publication. The accumulated results from spectroscopic and microscopic investigations demonstrated that water molecules confined within nanoscopic enclosure of the self-assembled reverse micelles played critical role in the redox processes of aurate ions to produce GNPs, which are assumed to have approximately constant size distributions. The resulting dye-functionalized GNPs were found to offer their absorption and fluorescence emission tunability by changing the medium polarity as well as to exhibit excellent film-forming properties to give optically homogeneous polystyrene thin films. These key findings in addition to broad applicability of the self-assembling process with a variety of dye analogues have led to a conclusion that the protocol presented here serves as a versatile synthetic method to provide a potential convenience for future development of new organic-inorganic hybrid nanomaterials.

A new approach toward the total synthesis of (+)-batzellaside B

Summary A new synthetic approach to (+)-batzellaside B from naturally abundant L-pyroglutamic acid is presented in this article. The key synthetic step involves Sharpless asymmetric dihydroxylation of an olefinic substrate functionalized with an acetoxy group to introduce two chiral centres diastereoselectively into the structure. Heterocyclic hemiaminal 4, which could be converted from the resulting product, was found to provide stereospecific access to enantiomerically enriched allylated intermediate, offering better prospects for the total synthesis of this natural product.

Novel chiral tetramic acid-derived diols: organocatalytic facile synthesis and unique structural properties

Organocatalytic tandem reactions of L-phenylalanine-derived tetramic acid with aldehydes allow a one-pot and high-yielding access to a diverse range of novel chiral diols in enantiomerically pure forms. In addition, a new entry of the diols, featuring their unique structures associated with C2- and pseudo C2-symmetric chiral motifs, is reported.

Developments in the Synthesis of 3-Acyltetramic Acid Natural Products

Abstract 3-Acyltetramic acids are a large and diversified family of fungal or bacterial metabolites that possess hybrid structures composed of amino acid and polyketide. They have attracted a great deal of interest among chemists and biologists because of their potential applications in drug discovery. Reported syntheses of them are classified into two categories according to their retrosynthetic analysis. One is the ring construction of tetramic acid core from polycarbonyl substrates, including Lacey–Dieckmann cyclization that is the most popular method for the preparation of 3-acyltetramic acids. The method imitating the biosynthetic transformation of amino acid into 3-acyltetramic acid consists of the introduction of a β-keto carbonyl function on the nitrogen atom of amino acid derivatives and following lactam formation via intramolecular Dieckmann cyclization. Many total syntheses of complicated natural products such as polycephalin C, macrocidin A and fusarisetin have been achieved by this approach. Another category is the acylation of 3-unsubstituted tetramic acids. Since this type of synthetic approach was reported in the late 1970s, only a few synthetic examples of simple 3-acyltetramic acids using strong Lewis acids such as BF 3 •OEt 2 or TiCl 4 are known so far. An alternative approach for the acylation could be achieved by employing a sequence of O-acylation of a 3-unsubstituted tetramic acid and O- to C-acyl rearrangement mediated by DMAP and neutral metal salts. This mild protocol was demonstrated to be quite effective through the convergent syntheses of natural products and their absolute structure determination.