Chemoselective Deprotection of Symmetrically Diprotected Resorcinol -Methyliminodiacetate (MIDA) Boronates Using the MIDA Boronate Moiety as a Blocking Group: Synthesis of Monoprotected Resorcinol MIDA Boronates.

A novel protocol for the synthesis of monoprotected resorcinol -methyliminodiacetate (MIDA) boronates was developed via the chemoselective deprotection of diprotected resorcinol MIDA derivatives with identical protecting groups, utilizing the MIDA boronate moiety as a blocking group for deprotection. This protocol exhibited a broad substrate scope, and the resulting MIDA boronates were readily isolated by simple filtration from the reaction mixture. Furthermore, the utility of this protocol was demonstrated by converting the resulting MIDA boronates into value-added chemicals containing resorcinol scaffolds.

Synthesis of 2-(2-nitrophenyl)indoline-3-acetic acid derivatives base-catalyzed cyclization of -(2-nitrobenzyl)-2-aminocinnamic acid derivatives.

A protocol for the synthesis of 2-(2-nitrophenyl)indoline-3-acetic acid derivatives was developed base-catalyzed cyclization of -(2-nitrobenzyl)-2-aminocinnamic acid derivatives. The synthetic utility of this methodology was illustrated by the concise synthesis of dihydropaullone, a partially saturated analog of paullone. Furthermore, the indoline scaffold could be further converted to the corresponding indoles and other indole-fused heterocycles.

Biomimetic hydrogel blanket for conserving and recovering intrinsic cell properties.

Background: Cells in the human body experience different growth environments and conditions, such as compressive pressure and oxygen concentrations, depending on the type and location of the tissue. Thus, a culture device that emulates the environment inside the body is required to study cells outside the body.

Methods: A blanket-type cell culture device (Direct Contact Pressing: DCP) was fabricated with an alginate-based hydrogel.

Asymmetric Total Synthesis of Iheyamine B.

Herein, we report the first asymmetric total synthesis of iheyamine B from 2,2'-bisindoloazepinone using the stereoselective construction of the -vicinal 2-oxopropyl moiety in the azepine scaffold. The asymmetric decarboxylative allylic alkylation provided the α-allylated 2,2'-bisindoloazepinone intermediate. The subsequent conversion of the lactam moiety into another allyl group in a -selective manner followed by Wacker oxidation of each allyl unit to the corresponding 2-oxopropyl group completed the total synthesis of iheyamine B.

A cyanide-catalyzed imino-Stetter reaction enables the concise total syntheses of rucaparib.

Two routes toward the synthesis of rucaparib, an FDA-approved drug used for the treatment of ovarian and prostate cancers, have been developed from commercially available starting materials utilizing the cyanide-catalyzed imino-Stetter reaction as the key step for the construction of the indole motif bearing all the desired substituents in their correct positions. In the first-generation synthesis, -fluorobenzoate, the starting material currently used in the process chemistry route of rucaparib, was converted into 4,6-disubstituted 2-aminocinnamic acid derivatives (ester or amide). The cyanide-catalyzed imino-Stetter reaction of aldimines derived from the resulting 2-aminocinnamic acid derivatives and a commercially available aldehyde afforded the desired indole-3-acetic acid derivatives.

Rapid Synthesis of Multifunctional Apatite via the Laser-Induced Hydrothermal Process.

Synthetic biomaterials are used to overcome the limited quantity of human-derived biomaterials and to impart additional biofunctionality. Although numerous synthetic processes have been developed using various phases and methods, currently commonly used processes have some issues, such as a long process time and difficulties with extensive size control and high-concentration metal ion substitution to achieve additional functionality. Herein, we introduce a rapid synthesis method using a laser-induced hydrothermal process.

Precisely Localized Bone Regeneration Mediated by Marine-Derived Microdroplets with Superior BMP-2 Binding Affinity.

Prompt and robust bone regeneration has been clinically achieved using supraphysiological doses of bone morphogenetic protein-2 (BMP-2) to overcome the short half-life and rapid clearance. However, uncontrolled burst release of exogenous BMP-2 causes severe complications such as heterotopic ossification and soft tissue inflammation. Therefore, numerous researches have focused on developing a new BMP-2 delivery system for a sustained release profile by immobilizing BMP-2 in various polymeric vehicles.

Total Synthesis of Rucaparib.

A concise total synthesis of rucaparib, an FDA-approved drug for ovarian and prostate cancers, is reported. The Heck reaction of the commercially available aryl iodide with acrylonitrile provided the desired ()-2-aminocinnamonitrile derivative. A subsequent imino-Stetter reaction of the aldimine derived from 2-aminocinnamonitrile and aldehyde furnished indole-3-acetonitrile bearing the desired substituents at appropriate positions.

A Stereodivergent Strategy for Total Syntheses of Antirhine Alkaloids.

Total syntheses of the antirhine alkaloids are described. The cyanide-catalyzed imino-Stetter reaction of the aldimine derived from ethyl 2-aminocinnamate and 4-bromopyridine-2-carboxaldehyde provided a 2-pyridinyl substituted indole-3-acetate, which was further converted into the corresponding indoloquinolizidinium intermediate through C-ring formation. Subsequent -selective installation of the homoallylic alcohol side-chain at C-15 in the resulting indoloquinolizidinium allowed the total syntheses of antirhine and its known epimer.

Total Synthesis of Hinckdentine A.

The total synthesis of (±)-hinckdentine A is described herein. A cyanide-catalyzed imino-Stetter reaction of the aldimine derived from ethyl 2-amino-3,5-dibromocinnamate and 5-bromo-2-nitrobenzaldehyde followed by oxidative rearrangement afforded a 2,2-disubstituted 3-indolinone derivative containing the carbon skeleton and all of the functional groups present in the natural product correctly positioned, including three bromine atoms. Subsequent D-ring formation and seven-membered C-ring construction completed the total synthesis of hinckdentine A.

Real-Time Reaction Monitoring with In Operando Flow NMR and FTIR Spectroscopy: Reaction Mechanism of Benzoxazole Synthesis.

In operando observation of reaction intermediates is crucial for unraveling reaction mechanisms. To address the sensitivity limitations of commercial ReactIR, a flow cell was integrated with a Fourier transform infrared (FTIR) spectrometer yielding a "flow FTIR" device coupled with an NMR spectrometer for the elucidation of reaction mechanisms. The former device detects the low-intensity IR peaks of reaction intermediates by adjusting the path length of the FTIR sample cell, whereas the flow NMR allows the quantitative analysis of reaction species, thus offsetting the limitations of IR spectroscopy resulting from different absorption coefficients of the normal modes.

Atroposelective Total Syntheses of Naphthylisoquinoline Alkaloids with ()-Configuration.

Asymmetric total syntheses of naphthylisoquinoline alkaloids with a ()-configuration are described. An atroposelective Suzuki-Miyaura reaction between naphthyl pinacol boronate and an aryl iodide bearing an ()-2-(-acetylamino)propyl group at the -position using Pd(OAc) in the presence of SPhos and Ba(OH) provided the ()-selective biaryl product as the major product without any external chiral sources. This biaryl product was converted into naphthylisoquinoline alkaloids with a ()-configuration via stereoselective construction of the isoquinoline framework with the appropriate oxidation state and stereochemistry.

Asymmetric Total Syntheses of Naphthylisoquinoline Alkaloids via Atroposelective Coupling Reaction Using Central Chirality as Atroposelectivity-Controlling Group.

We describe the asymmetric total syntheses of naphthylisoquinoline alkaloids. Atroposelective biaryl coupling reaction between naphthyl pinacol boronate and an aryl iodide, bearing ()-2-aminopropyl group at the -position using the existing central chirality as an atroposelectivity-controlling group, provided the desired biaryl product with high atroposelectivity, without the use of an external chiral source. From the resulting biaryl product, several naphthylisoquinoline alkaloids were prepared via the stereoselective formation of the isoquinoline framework with the appropriate oxidation state and stereochemistry.

Total Synthesis of Iheyamine A via the Cyanide-Catalyzed Imino-Stetter Reaction.

The total synthesis of iheyamine A from readily available ethyl 2-aminocinnamate and 5-methoxyindole-2-carboxaldehyde is described. The cyanide-catalyzed imino-Stetter reaction of an aldimine derived from ethyl 2-aminocinnamate and 5-methoxyindole-2-carboxaldehyde provided the desired unsymmetrical 2,2'-bisindole-3-acetic acid derivative. The subsequent introduction of an amino group at the C-3' position, followed by the formation of the azepine ring, completed the total synthesis of iheyamine A.

General Strategy for the Synthesis of Antirhine Alkaloids: Divergent Total Syntheses of (±)-Antirhine, (±)-18,19-Dihydroantirhine, and Their 20-Epimers.

A general synthetic strategy for antirhine alkaloids was developed in this study. The cyanide-catalyzed imino-Stetter reaction of ethyl 2-aminocinnamate and 4-bromopyridine-2-carboxaldehyde afforded the corresponding indole-3-acetic acid derivative. Subsequent formation of the six-membered C ring followed by -selective installation of the two-carbon unit at C-15 provided rapid access to the key intermediate.

Synthesis of V-doped InO Nanocrystals via Digestive-Ripening Process and Their Electrocatalytic Properties in CO Reduction Reaction.

The development of synthetic methods for monodisperse nanomaterial is of great importance in science and technology related to nanomaterials. The strong demands to prepare exceptionally monodisperse nanocrystals have made digestive-ripening one of the most sought-after size-focusing processes. Although digestive-ripening processes have been demonstrated to produce various metals and semiconductors, their applicability to oxides has rarely been studied despite various unique properties and applications of oxide nanomaterials.

Total Synthesis of Phenanthroquinolizidine Alkaloids Using a Building Block Strategy.

A concise and general strategy for the total synthesis of the phenanthroquinolizidine alkaloids has been developed. An iterative Suzuki-Miyaura coupling reaction between the requisite aryl boronic acid, 2-bromo-4,5-dimethoxyphenyl -methyliminodiacetate (MIDA) boronate derived from boronic acid, and a suitable bromopyridine substrate bearing a homopropargyl alcohol at the 2-position generated the desired -aza-terphenyl compounds. Hydrogenation of the triple bond followed by treatment with methanesulfonyl chloride afforded their corresponding tetrahydroquinolizinium ion intermediates, which were subsequently reacted with NaBH to provide the desired hexahydroquinolizine products.

Modular Syntheses of Phenanthroindolizidine Natural Products.

A highly concise strategy for the total synthesis of phenanthroindolizidines was developed. The one-pot iterative Suzuki-Miyaura reaction of aryl boronic acids with ortho-bromoaryl N-methyliminodiacetate (MIDA) boronate followed by a second Suzuki-Miyaura reaction with a suitable pyridyl bromide provided ortho-aza-terphenyls. Subsequent saturation of the triple bond, treatment with mesyl chloride, and reduction of the resulting dihydroindolizidinium ring afforded the hexahydroindolizines.

On-Water Synthesis of 2-Substituted Quinolines from 2-Aminochalcones Using Benzylamine as the Nucleophilic Catalyst.

On-water synthesis of 2-substituted quinolines from 2-aminochalcone derivatives was developed using benzylamine as the nucleophilic catalyst. Various 2-aminochalcones could be applied to this protocol, and the desired 2-substituted quinoline products were isolated in excellent yields by simple filtration. Furthermore, we elucidated the role of benzylamine in this transformation and provided the detailed reaction mechanism.

Enantioselective Synthesis of Tetrahydroquinolines from 2-Aminochalcones via a Consecutive One-Pot Reaction Catalyzed by Chiral Phosphoric Acid.

A new asymmetric protocol for the synthesis of chiral tetrahydroquinolines from 2-aminochalcones via a two-step one-pot consecutive process (cyclization/asymmetric reduction) has been developed using chiral phosphoric acid as the sole catalyst. 2-Aminochalcones were converted into the corresponding quinolines through chiral phosphoric acid-catalyzed dehydrative cyclization, and the resultant quinolines were subsequently reduced to the chiral tetrahydroquinolines via chiral phosphoric acid-catalyzed asymmetric reduction with Hantzsch ester. Various 2-aminochalcones could be applicable to this protocol, and the desired tetrahydroquinolines were obtained in excellent yields and with excellent enantioselectivities.

Chemistry of Cyanide Adducts of Aldimines from Aniline Derivatives.

The chemistry of hydrogen cyanide adducts of imines is well-developed, but that of cyanide adducts remains unexplored. This is presumably because these cyanide adducts are not stable and thus not readily available in their isolated forms. In this personal account, we present the progress made in our research program towards the development of novel organic transformations utilizing cyanide adducts of imines as key intermediates.

Synthesis of 2-Substituted Quinolines from 2-Aminostyryl Ketones Using Iodide as a Catalyst.

A new protocol for the synthesis of 2-substituted quinolines from 2-aminostyryl ketones has been developed using iodide as a nucleophilic catalyst. Conjugate addition of iodide to 2-aminostyryl ketones yielded the corresponding β-iodoketones, which could have a conformation where the amino and carbonyl groups are proximal through free rotation about the C-C single bond. Subsequent condensation between the amino and carbonyl groups followed by elimination of hydrogen iodide provided the corresponding quinolines, with regeneration of the iodide catalyst.

A general strategy for the synthesis of indoloquinolizine alkaloids via a cyanide-catalyzed imino-Stetter reaction.

A new strategy applicable to the synthesis of indoloquinolizine natural products has been developed. A cyanide-catalyzed intramolecular imino-Stetter reaction of aldimines, derived from 2-aminocinnamic acid derivatives and 2-pyridinecarboxaldehydes, provided indole-3-acetic acid derivatives bearing a pyridyl ring at the 2-position. Reduction of the carboxylic acid moiety to an alcohol followed by activation of the resulting alcohol with TfO or TsCl generated indoloquinolizinium salts, which were utilized as precursors for indoloquinolizine natural products.

Total Syntheses of Arcyriaflavin A and Calothrixin B Using 2,2'-Bisindole-3-acetic Acid Derivative as a Common Intermediate.

A new protocol for the synthesis of 2,2'-bisindole-3-acetic acid derivatives from aldimines derived from 2-aminocinnamic acid derivatives and indole-2-carboxaldehyde was developed via a cyanide-catalyzed imino-Stetter reaction. With this protocol, the divergent total syntheses of arcyriaflavin A, a representative indolocarbazole natural product, and calothrixin B, a representative indolo[3,2-j]phenanthridine natural product, were completed using a 2,2'-bisindole-3-acetic acid derivative as the common intermediate.

Total Synthesis of Luotonin A and Rutaecarpine from an Aldimine via the Designed Cyclization.

The total synthesis of rutaecarpine (1) and luotonin A (2) is described through controlled cyclization of a common aldimine intermediate 5 derived from ethyl-2-aminocinnamate and quinazolinone-2-carbaldehyde. The cyanide-mediated imino-Stetter reaction of aldimine 5 provided the corresponding indole derivative 3, from which the total synthesis of rutaecarpine (1) was completed via the formation of a 6-membered C-ring. On the other hand, microwave-assisted thermal 6π-electrocyclization of the common intermediate 5, followed by the formation of a 5-membered C'-ring, allowed the completion of the total synthesis of luotonin A (2).