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Volume 69, Issue 5
Displaying 1-17 of 17 articles from this issue
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Preface
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Kiyoshi Tomioka2011 Volume 69 Issue 5 Pages 483
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL OPEN ACCESSDownload PDF (580K)
Reviews and Accounts
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Noboru Sayo2011 Volume 69 Issue 5 Pages 484-492
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSCatalyst developments so as to improve synthetic process are described. Efforts focused in this article include: Design of a catalyst which gives higher catalytic activities and enantioselectivities, development of a new reaction that can bypass a conventional synthetic route, and creation of new catalytic reaction that can replace stoichiometric reactions. These efforts contribute to reduction of cost, waste, and production time. Exemplified herein are: (1)SEGPHOS® ligands that enhanced catalytic activity and selectivity, (2)direct reductive amination that enabled short-cut process en route to β-amino acids from the β-ketoesters, (3)catalytic ester reduction with hydrogen gas that circumvents the use of stoichiometric amounts of metal hydrides, and (4)a Zn cluster catalyst that mediates catalytic acylation and deacylation.View full abstractDownload PDF (1340K) -
Takao Teshima2011 Volume 69 Issue 5 Pages 493-498
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSIn development of a manufacturing process for drug candidate, to ensure the safety of manufacturing is required for process chemists. It’s one of the useful procedures to understand the reaction behavior for the purpose of the safety consideration. In a process development for a ketone reduction with NaBH4/MeOH, we measured the reaction behavior of using a reaction calorimetry (RC1eTM), gas measurement devise and in situ particle counter (FBRM®). It was found that the combination of these reagents has the induction period and latent, abrupt release of heat and gas evolution. Furthermore, the measurement of the particle counts revealed that the induction period was caused by the insolubility of NaBH4 in THF and the disproportionation of NaBHx(OMe)4-x to NaBH4.View full abstractDownload PDF (1232K) -
Kazuhiko Saigo, Kenichi Sakai2011 Volume 69 Issue 5 Pages 499-505
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSIn order to overcome trial-and-error situation in the enantioseparation by the diastereomeric salt formation, we carried out systematic studies on the enantioseparation of racemic 1-arylethylamines with/without a substituent on the aryl group by using enantiopure arylglycolic acids. The studies revealed that there are three factors for the growth and stabilization of less-soluble diastereomeric salt crystals; 1)infinite hydrogen bonding interaction to form a 21-column, which enables a crystal to grow in one dimension, 2)effective van der Waals interaction between the columns to make the crystal growable in a three-dimensional manner, and 3)sufficient CH-π interaction in/between the columns, which also play an important role for three-dimensional crystal growth. On the basis of the observations, we propose molecular length rule and aromatic ring rule, which realize efficient van der Waals interaction and CH-π interaction, respectively.
Keeping in mind of these requirements for the molecular structure of a resolving agent, we industrialized an elegant process for the enantioseparation of racemic 1-phenylethylamine into the (R)-form, which is one of the most valuable chiral auxiliaries in the synthesis of drugs/drug intermediates in industrial scales, with (R)-mandelic acid upon optimizing conditions such as solvent, molar ratio, concentration, temperature, and additive, as well as the recycling process of (R)-mandelic acid and the racemizing process of (S)-1-phenylethylamine remained.View full abstractDownload PDF (912K) -
Yoshihiko Hirose2011 Volume 69 Issue 5 Pages 506-516
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSBiocatalysts are versatile tools for the quick synthesis of single enantiomers by not only kinetic resolution of racemates but desymmetrization of prochiral substrates. However, the theoretical yield of resolution is 50%. To circumvent the problem, enzymatic or non-enzymatic racemization method are investigated. Dynamic kinetic resolution (DKR) will be able to afford the desired product with high chemical yield and high enantiomeric excess in a one-pot reaction. Multi-enzyme system is an effective method. The combination of two types of dehydrogenases is useful to obtain secondary alcohols and amines. The utilization of genetically modified microorganism, in which the genes of those dehydrogenases are inserted, is an attractive synthetic process as whole cell biocatalysts.View full abstractDownload PDF (1469K) -
Motoko Hayashi2011 Volume 69 Issue 5 Pages 517-525
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSChiralscreen® is biocatalyst, i.e. enzyme for asymmetric synthesis. Chiralscreen® OH for chiral alcohols and Chiralscreen® NH for chiral amino acids and amines are available. It catalyzes the desired reaction in high regio/stereo selectivity under mild conditions without dangerous reagents. For example, chemical reduction requires hydride reagent or hydrogen, however, pseudo-hydride donor of reduction with Chiralscreen® is formate or glucose. The solvent is water, and the reactions proceeds under ambient pressure and room temperature. Therefore, special facilities and safety counterplans are not needed for the reactions. The solubility of substrate in the water is not essential for the reaction. We have an example that slightly soluble ketone (solubility in water is 0.05%) is reduced quantitatively in perfect selectivity. Chiralscreen® is produced using recombinant cell, however, endotoxin, DNA, and/or proteins derived from microbe are not detected in the product.View full abstractDownload PDF (1022K) -
Tatsuhiro Yamamoto, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori2011 Volume 69 Issue 5 Pages 526-533
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSIntegrated micro chemical systems on a chip have been attractive as evolutional tools for high speed, functional and compact instrumentation for chemical analysis, organic synthesis and many others. We have established micro unit operations (MUOs) and applied them to continuous flow chemical processing (CFCP). Recently, the space size of the system is further downscaled to 101-102nm, which we call extended nano space. We have developed fundamental research tools for the extended-nano space, located between conventional nanotechnology (100-101nm) and microtechnology (>1µm) and have been studying this space as new research field. In this review, we focus on the methodology and application of integrated micro- and nano-chemical systems for chemical processing, organic synthesis and other applications.View full abstractDownload PDF (2293K) -
Shinji Hasebe2011 Volume 69 Issue 5 Pages 534-541
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSMicro devices have large specific surface area. This feature can be effectively used to control the residence time and the temperature in the devices. In the manuscript, the feature of the design and operation problems of micro chemical plant is discussed. First, it is explained that the temperature and residence time can be controlled precisely in micro devices by using examples. Then, the importance of optimal shape design is stressed using a case study of exothermic reaction.
In most cases, the flow rate of single channel is not enough for real production. The numbering-up is dominant method for micro plant to increase the flow rate. The feature of several numbering-up method is explained and the desirable numbering-up procedure is proposed. The blockage of the channels is a dominant abnormal condition for micro devices. Therefore, to achieve the stable long-term operation of micro chemical plants it is very important to detect the blockage of the channels as early as possible. It is not practical to install the sensors in all the parallel channels from the standpoint of measuring device cost. A distributer structure that can detect and diagnose a blocked channel has been proposed. In the proposed system, two flow sensors are enough for detecting the blocked channel even when the process consists of 4 to 8 parallel channels. Furthermore, a flow control system that ensures the steady state operation for each of the parallel devices during the replacement of the device in the blocked channel is proposed.View full abstractDownload PDF (1536K) -
Yoichi M. A. Yamada, Yasuhiro Uozumi2011 Volume 69 Issue 5 Pages 542-551
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSHighly active and reusable solid-phase catalysts were developed with our ‘molecular convolution methodology’ where a soluble linear polymer having multiple ligand groups was convoluted with transition metals via coordinative or ionic complexation to achieve the one-step preparation of the insoluble polymeric metal composite. These convoluted polymeric-palladium nanoparticles, -phosphotungstate salt, and -palladium complex promoted the organic transformations with high reusability to give the corresponding products quantitatively.
Moreover, instantaneous catalytic cross-coupling reactions were achieved in the catalytic membrane-installed microchannel devices having a polymeric palladium complex membrane. The catalytic membrane-installed microchannel devices were installed inside the microchannels via the molecular convolution at the interface between the organic and aqueous phases flowing laminarly. The microflow device-catalyzed Suzuki-Miyaura reaction was performed at 50°C to give the product quantitatively within 5 sec of residence time. They were applied to the allylic arylation at 70°C to afford the corresponding products quantitatvely within 1 sec of residence time.View full abstractDownload PDF (4130K) -
Masaru Utsunomiya, Yusuke Izawa, Miwako Nakatani2011 Volume 69 Issue 5 Pages 552-561
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSDevelopment of reactions and processes using homogeneous, late metal catalysts are summarized. Homogeneous catalyst shows unique reactivity and selectivity, but its application to industrial process is still limited. Industrial process requires not only high reaction yields, but also high catalyst stability, easy separation and small amount of by-products. Two types of general processes of homogeneous catalyst are presented in this article. One is a process with highly stable catalyst and that process recycles the stable catalyst. The other is a process uses highly active catalyst without catalyst recycle. Ruthenium-catalyzed dehydrogenation of 1,4-butanediol to produce γ-lactone is developed as the process of highly stable catalyst. Development of the process using highly active palladium-catalyst for isomerization of allylic esters without catalyst recycle is also developed.View full abstractDownload PDF (1464K) -
Tetsuya Ikemoto2011 Volume 69 Issue 5 Pages 562-570
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSRecent developments of organocatalysis and their applications to process chemistry have been described. Especially, three kinds of organocatalysts, a proline catalyst, the diarylprolinol silyl ether catalysts developed by Jørgensen’s group and Hayashi’s group independently (Jørgensen-Hayashi catalysts), and the bifunctional thiourea catalysts developed by Takemoto’s group have been taken up here and discussed. Our applications to the practical synthesis of the intermediate of (S)-Oxybutynin, the intermediate of anti-AIDS drug BFOL, and (R)-Baclofen were also introduced in this review.View full abstractDownload PDF (1125K) -
Yasushi Murai, Kunio Atsumi2011 Volume 69 Issue 5 Pages 571-578
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSWe had studied a new synthetic route to 7α-methoxycephalosporins, and completed in the first half of the 1980’s. The synthetic route was adopted for the industrial process of cefminox, a cephamycin-group antibiotic, which had been developed by Meiji Seika Kaisha and was launched in 1987. In this article, the process of the study to the success including attempts not to succeed was described in detail.View full abstractDownload PDF (1064K) -
Nobuyoshi Yasuda, Artis Klapars, Yoshinori Kohmura, Kevin R. Campos, H ...2011 Volume 69 Issue 5 Pages 579-588
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSThe hNK-1 antagonist candidate 3 is synthetically one of most challenging antagonist candidates at Merck, having six chiral centers. The ether bond was formed via π-allyl palladium chemistry with the zinc alkoxide of the chiral alcohol and chiral 2-cyclopenten-1-ol, prepared via enzymatic reduction of the corresponding ketone, to set two chiral centers. 4-Fluorophenyl group was introduced to the cyclopentene ring via 1,4-addition in a stereospecific manner. The δ-lactam having the quaternary chiral amine function was embedded onto the cyclopentane ring using Seebach’s chiral oxazolidinone. In this article, scalable synthesis of 3 is described in a chronological order.View full abstractDownload PDF (1295K) -
Chisa Ohta, Shinitsu Kuwabe2011 Volume 69 Issue 5 Pages 589-599
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSThis manuscript describes a highly efficient and practical method for the synthesis of exquisite EP4-receptor agonist ONO-4819 that is expected for a therapeutic agent of metabolic bone diseases. The first generation stereoselective synthesis of ONO-4819 was developed using a commercially available THP-protected Corey-lactone as a starting material. Although the first generation synthesis was suitable for manufacturing more than 500 g of ONO-4819 for an initial study, it suffered from several drawbacks, one of which was a transformation to introduce sulfur-containing C4 side chain accompanied by the formation of three troublesome byproducts. In the second generation study, the authors have developed an improved synthetic route to introduce sulfur-containing C4 side chain using pure γ-thiobutyrolactone to suppress those side-products. Furthermore, benzoyl and tert-butyldimethylsilyl groups as protecting group for hydroxyl functions are used for precise process controls of all intermediates. Thus, an improved robust process for ONO-4819 with a high chemical purity has been developed.View full abstractDownload PDF (1168K) -
Hiroyuki Chiba, Katsuya Tagami2011 Volume 69 Issue 5 Pages 600-610
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSHALAVENTM (eribulin mesylate, E7389) is a novel anticancer agent discovered and developed by Eisai, which was approved by the United States Food and Drug Administration (FDA) for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. HALAVENTM is a non-taxane, microtubule dynamics inhibitor and a synthetic analog of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Although the structure of HALAVENTM is substantially simplified relative to halichondrin B, the development of this complex molecule only by chemical synthesis represents a significant challenge in terms of pharmaceutical development. In this article, a developmental history of HALAVENTM from its discovery to process development aiming at commercial production is described.View full abstractDownload PDF (1474K)
Crossroad
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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...2011 Volume 69 Issue 5 Pages 611
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL OPEN ACCESSDownload PDF (544K)
Practice of Reaction Mechanism
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[in Japanese]2011 Volume 69 Issue 5 Pages 613-614
Published: May 01, 2011
Released on J-STAGE: July 11, 2011
JOURNAL RESTRICTED ACCESSDownload PDF (543K)
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