Enantioselective Synthesis of Secondary Amines by Combining Oxidative Rearrangement and Biocatalysis in a One-Pot Process.

This contribution describes the development of chemoenzymatic one-pot processes, which combine an oxidative rearrangement and a biotransformation catalyzed by an imine reductase (IRED), for the synthesis of highly enantiomerically enriched secondary amines, such as an aryl-substituted pyrrolidine and a benzazepine. The benefits of this chemoenzymatic one-pot approach include high overall conversions (up to >99%), high enantiomeric excesses (up to >99% ), and a straightforward synthetic approach toward secondary amines without the need to isolate the formed intermediate. For the initial chemical reaction, namely, the oxidative rearrangement, PhI(OAc) in methanol is used as a non-natural reagent, whereas the enzymatic step requires only stoichiometric amounts of d-glucose along with catalytic amounts of IRED, glucose dehydrogenase (GDH), and the cofactor NADPH.

Total Synthesis and Antibacterial Activity of Marine Tris-indole Alkaloid Tulongicin A.

Bis-indole alkaloids from marine sponges are an intriguing class of natural products with a variety of activities. However, only a preliminary biological study of tulongicin A (), a related previously isolated marine tris-indole alkaloid, has been conducted. In this study, we accomplished the first asymmetric total synthesis of via the construction of an imidazoline-linked bis-indolylmethane skeleton using a Friedel-Crafts-type reaction.

Axially Chiral Borinic Acid Catalysts: Design, Synthesis, and Application in Alkylative Desymmetrization of 1,2-Diols.

A novel chiral borinic acid (CBA), an organocatalyst possessing a binaphthyl skeleton, was designed and synthesized. The synthesis of CBA was achieved with a 72% yield in four steps starting with optically pure 1,1'-bi-2-naphthol. The asymmetric catalytic activity was investigated in the desymmetrization of -1,2-diol.

Heteroannulation of bicyclobutane derivatives Au-catalyzed hydration to enol ethers and intramolecular cyclization giving spirocyclobutanes.

We report the heteroannulations of bicyclobutane derivatives bearing enol ether groups in the presence of HO under mild conditions. The reaction affords spirocyclobutanes with cyclic acetal groups the Au-catalyzed hydration of the enol ether group and subsequent intramolecular cyclization.

Synthesis and Biological Evaluation of Simplified Ansellone Analogues with Lipophilic Side Chains as HIV Latency-Reversing Agents.

Structurally simplified analogues of ansellone A, in which the decalin skeleton is replaced with a lipophilic chain, were prepared and their HIV latency-reversing activities biologically evaluated. In particular, two analogues bearing ether and alkenyl side chains, respectively, showed comparable activities to that of ansellone A. Each of the simplified compounds was easily synthesized using Prins cyclisation chemistry.

Palladium-Catalyzed Intramolecular Migratory Cycloisomerization of 3-Phenoxy Acrylic Acid Ester via C-O Bond Cleavage and C-O/C-C Bonds Formation for 2,3-Disubstituted Benzofurans Synthesis.

Migratory cycloisomerization using transition metal catalyst is useful for synthesizing substituted heterocyclic compounds. We achieved palladium-catalyzed migratory cycloisomerization of 3-o-alkynylphenoxy acrylic acid ester derivatives to give 2,3-disubstituted benzofurans. Although there are several reports of benzofuran synthesis with palladium-catalyzed migratory cycloisomerization, migratory groups are limited to allyl and propargyl groups.

Double Ring Expansion Strategy for Fused 3-Benzazepines: Alternative Synthesis of the Dolby-Weinreb Enamine.

A double ring expansion strategy for constructing fused 3-benzazepines is described. The oxidative ring expansion of spiroamine compounds with -chlorosuccinimide and subsequent ring expansion of the resulting ketiminium ion intermediates with trimethylsilyldiazomethane afforded fused 3-benzazepines in a one-pot operation. Importantly, the Dolby-Weinreb enamine, which is a key synthetic intermediate for harringtonine alkaloids, cephalotaxines, can be accessed from commercial materials in only two steps using our developed method.

Physiological concentrations of glucocorticoids induce pathological DNA double-strand breaks.

Steroid hormones induce the transcription of target genes by activating nuclear receptors. Early transcriptional response to various stimuli, including hormones, involves the active catalysis of topoisomerase II (TOP2) at transcription regulatory sequences. TOP2 untangles DNAs by transiently generating double-strand breaks (DSBs), where TOP2 covalently binds to DSB ends.

Design, Synthesis, and Monoamine Oxidase B Selective Inhibitory Activity of -Arylated Heliamine Analogues.

Monoamine oxidase B (MAO-B) metabolizes monoamines such as dopamine regarding neural transmission and controls its level in the mammalian's brain. When MAO-B metabolizes dopamine abnormally, normal neurotransmission does not occur, and central nervous system disorders such as Parkinson's disease may develop. Although several MAO inhibitors have been developed, most of them have no selectivity between monoamine oxidase A (MAO-A) and MAO-B, or they work irreversibly against the enzyme.

Iridium-Catalyzed Isomerization/Cycloisomerization/Aromatization of -Allyl--sulfonyl--(λ-silylethynyl)aniline Derivatives to Give Substituted Indole Derivatives.

We have developed a one-iridium-catalyst system that transforms -allyl--sulfonyl-2-(silylalkynyl)aniline derivatives, which are 1,7-enynes in which both multiple bonds have a heteroatom, to the corresponding substituted indole derivatives via isomerization/cycloisomerization/aromatization. This strategy provides an atom-economical and straightforward synthetic approach to a series of valuable indoles having vinyl and silylmethyl groups at the 2- and 3-positions.

Total Synthesis and Biological Evaluation of the Potent HIV Latency-Reversing Agent Ansellone A and its Analogues.

The total synthesis and biological evaluation of the marine sesterterpenoid ansellone A (), an HIV latency-reversing agent, and its analogues are reported. The key to the success of this synthetic route is a Prins cyclization reaction enabled by the strategic use of the TfO group for stabilization of the acid-labile tertiary allylic alcohol. The SAR study found the alcohol analogue to exhibit more potent activity than .

Selective Reduction of α,β-Unsaturated Weinreb Amides in the Presence of α,β-Unsaturated Esters.

α,β-Unsaturated esters were selectively protected in situ in the presence of α,β-unsaturated Weinreb amides using PEt and trimethylsilyl trifluoromethanesulfonate (TMSOTf) in toluene under reflux. Diisobutylaluminium hydride (DIBAL-H) reduction of the mixture followed by tetra-n-butylammonium fluoride (TBAF) treatment produced α,β-unsaturated aldehydes in good yields along with the recovered α,β-unsaturated esters.

Ring-opening 1,3-arylboration of arylcyclopropanes mediated by BCl.

Herein, we report a ring-opening 1,3-arylboration of aryl cyclopropanes using BCl in the presence of arene nucleophiles. Formal 1,3-oxy arylation and 1,3-amino arylation of the arylcyclopropane one-pot derivatization of the installed boron group were also achieved.

Iridium-Catalyzed Intramolecular Cycloisomerization between Functionalized Alkyne with Aryl Vinyl Ether: Synthesis of 2-Vinyl-3-functionalized Methylbenzofurans.

We have developed cycloisomerization between an aryl vinyl ether and a functionalized alkyne, such as silylalkyne, to give 2,3-disubstituted benzofuran derivatives using [IrCl(cod)], PCy, and NaBAr. This catalyst system not only catalyzes the above cycloisomerization but also isomerize a terminal olefin to give an aryl vinyl ether.

Design and Synthesis of 1,2-Deoxy-pyranose Derivatives of Spliceostatin A toward Prostate Cancer Treatment.

We designed and synthesized a novel 1,2-deoxy-pyranose and terminal epoxide methyl substituted derivatives of spliceostatin A using Julia-Kocienski olefination as a key step. With respect to the biological activity, the 1,2-deoxy-pyranose analogue of spliceostatin A suppressed AR-V7 expression at the nano level (IC = 3.3 nM).

Absorption, Fluorescence, and Two-Photon Excitation Ability of 5-Phenylisolidolo[2,1-]quinolines.

We report on the absorption, fluorescence, and two-photon excitation spectra of a series of 5-phenylisoindolo[2,1-]quinoline dyes. Depending on the substituents, we observed increasing two-photon absorption cross sections, with values up to 56 GM@973 nm, which are similar to those of the enhanced green fluorescent protein and fluorescein, common fluorescent chromophores.

Direct synthesis of dialkylarylvinylsilane derivatives: metathesis of dialkylaryl-iso-propenylsilane and its application to tetracyclic silacycle dye synthesis.

The metathesis of dialkylarylvinylsilane, which has not been accomplished to date, is achieved using dialkylaryl-iso-propenylsilane as a substrate. In addition, we discovered that the reason why the metathesis of a ruthenium carbene complex and dialkylarylvinylsilane is difficult is the formation of a carbide complex.

Ni-Catalyzed Cycloisomerization between 3-Phenoxy Acrylic Acid Derivatives and Alkynes via Intramolecular Cleavage and Formation of the C-O Bond To Give 2,3-Disubstituted Benzofurans.

Reactions based on transition-metal-catalyzed C-O bond cleavage have attracted much attention as a new synthetic method. Until now, several intermolecular reactions via C-O bond cleavage of aryl ethers, alkenyl ethers, esters, and others have been reported. Here we report an unprecedented C-O bond cleavage of 3-phenoxy acrylic acid derivatives, followed by intramolecular C-O bond formation with alkynes.

Chemoselective Transformations of Aromatic Methoxymethyl Ethers Using Trialkylsilyl Triflate and 2,2'-Bipyridyl.

Aromatic methoxymethyl (MOM) ethers behave differently from aliphatic MOM ethers upon treatment with trialkylsilyl triflate (RSiOTf) and 2,2'-bipyridyl. The aromatic MOM ethers are first converted to silyl ethers and subsequently deprotected by hydrolysis to give the mother alcohols when the RSiOTf used is trimethylsilyl triflate (TMSOTf). Conversely, direct conversion of aromatic MOM ethers to aromatic triethylsilyl (TES) ethers is possible when the RSiOTf used is triethylsilyl triflate (TESOTf).

Pd-Catalyzed Migratory Cycloisomerization of N-Allyl- o-allenylaniline Derivatives.

The Pd-catalyzed migratory cycloisomerization of N-allyl- o-allenyl aniline derivatives is first reported to give indoles having a substituent at the 2-position.

Oxidative Rearrangement of Primary Amines Using PhI(OAc) and CsCO.

An oxidative rearrangement of primary amines mediated by a hypervalent iodine(III) reagent is herein reported. The combination of PhI(OAc) and CsCO proves highly efficient at inducing the direct 1,2-C to N migration of primary amines, which can be applied to the preparation of both acyclic and cyclic amines. A mechanistic study shows that the rearrangement proceeds via a concerted mechanism.

Design and synthesis of N,N-diacetylspermidine analogues having a linker with desired functional groups.

The synthesis of new N1,N8-diacetylspermidine (DiAcSpd) analogues having a linker with desired functional groups in the methylene skeleton, which have been designed by theoretical calculations, is described. We have also achieved the preparation of DiAcSpd supported on solid-phase resins, which have the potential to be used for the evolution of ligands by exponential enrichment (SELEX).

Highly Discriminative and Chemoselective Deprotection/Transformations of Acetals with the Combination of Trialkylsilyl Triflate/2,4,6-Collidine.

Acetals are the most useful protecting groups for carbonyl functional groups. In addition to the role of protection, they can also be used as synthons of carbonyl functions. Previously, we developed a chemoselective deprotection and nucleophilic substitution of acetals from aldehydes in the presence of ketals.