研究者詳細 - 門田　功

Unified Total Synthesis, Stereostructural Elucidation, and Biological Evaluation of Sarcophytonolides 査読

Total Synthesis of Scabrolide F 査読国際誌

Hiroyoshi Takamura, Yuki Sugitani, Ryohei Morishita, Isao Kadota

Organic Letters 24 ( 42 ) 7845 - 7849 2022年10月

Chemical Synthesis and Biological Effect on Xylem Formation of Xylemin and Its Analogues 査読国際誌

Hiroyoshi Takamura, Hiroyasu Motose, Taichi Otsu, Shiori Shinohara, Ryugo Kouno, Isao Kadota, Taku Takahashi

European Journal of Organic Chemistry 2020 ( 18 ) 2745 - 2753 2020年5月

Hiroyoshi Takamura, Isao Kadota

Journal of Synthetic Organic Chemistry, Japan 77 ( 12 ) 1190 - 1200 2019年12月

Stereocontrolled synthesis of the macrolactone core of neopeltolide 査読

Andreas Meissner, Nobuhiro Tanaka, Hiroyoshi Takamura, Isao Kadota

Tetrahedron Letters 60 ( 5 ) 432 - 434 2019年1月

Formal total synthesis of enigmazole A 査読

Andreas Meissner, Takayuki Kishi, Yuka Fujisawa, Yuto Murai, Hiroyoshi Takamura, Isao Kadota

Tetrahedron Letters 59 ( 51 ) 4492 - 4495 2018年12月

Unified Total Synthesis, Stereostructural Elucidation, and Biological Evaluation of Sarcophytonolides 査読

Takamura, Hiroyoshi, Kikuchi, Takahiro, Iwamoto, Kohei, Nakao, Eiji, Harada, Naoki, Otsu, Taichi, Endo, Noriyuki, Fukuda, Yuji, Ohno, Osamu, Suenaga, Kiyotake, Guo, Yue-Wei, Kadota, Isao

Journal of Organic Chemistry 83 ( 18 ) 11028 - 11056 2018年9月

Improved Synthesis of the A–E Ring Segment of Ciguatoxin CTX3C by Using Intramolecular Allylations 査読

Tokihiro Tanaka, Hiroki Asakura, Rie Fujiwara, Kentaro Kumamoto, Hiroaki Izuka, Kengo Shiroma, Hiroyoshi Takamura, Isao Kadota

Bulletin of the Chemical Society of Japan 91 ( 4 ) 507 - 514 2018年4月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：The Chemical Society of Japan

An improved synthesis of the AE ring segment of ciguatoxin CTX3C is described. The E ring segment was synthesized by the intramolecular reaction of allylic stannane and aldehyde with high stereoselectivity. Construction of the AE ring framework was performed by using the intramolecular allylation of α-acetoxy ether followed by ring-closing metathesis.

DOI： 10.1246/bcsj.20170390

Convergent total synthesis of (−)-dactylolide 査読

Tokihiro Tanaka, Yuto Murai, Takayuki Kishi, Hiroyoshi Takamura, Isao Kadota

Tetrahedron Letters 59 ( 8 ) 763 - 766 2018年2月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

A convergent total synthesis of (−)-dactylolide is described. Constructing the 2,6-disubstituted exo-methylene THP moiety was achieved by the intramolecular allylation of α-acetoxy ether. The cyclization precursor was prepared from two segments, an alcohol and carboxylic acid derivatives, by esterification followed by reductive acetylation.

DOI： 10.1016/j.tetlet.2018.01.034

Total Synthesis of Rhoiptelol B 査読

Isao Kadota, Nobuhiro Tanaka, Hiroyoshi Takamura

HETEROCYCLES 97 ( 2 ) 1157 - 1157 2018年

Total Synthesis of Two Possible Diastereomers of Natural 6-Chlorotetrahydrofuran Acetogenin and Its Stereostructural Elucidation 査読

Hiroyoshi Takamura, Tomoya Katsube, Kazuki Okamoto, Isao Kadota

Chemistry - A European Journal 23 ( 68 ) 17191 - 17194 2017年12月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley-VCH Verlag

The first total synthesis of two possible diastereomers of natural 6-chlorotetrahydrofuran acetogenin 1 has been achieved. The synthetic route features 5-exo-tet cyclization, Z selective Wittig reaction and Julia olefination for the construction of conjugated diene and enyne moieties, and stereoselective chlorination. Comparison of their 1H and 13C NMR data and specific rotation with those of the natural product elucidated the absolute configuration of natural (−)-6-chlorotetrahydrofuran acetogenin 1.

DOI： 10.1002/chem.201703234

Late-stage divergent synthesis and antifouling activity of geraniol-butenolide hybrid molecules 査読

Hiroyoshi Takamura, Takumi Ohashi, Takahiro Kikuchi, Noriyuki Endo, Yuji Fukuda, Isao Kadota

Organic and Biomolecular Chemistry 15 ( 26 ) 5549 - 5555 2017年

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Royal Society of Chemistry

Hybrid molecules consisting of geraniol and butenolide were designed and synthesized by the late-stage divergent strategy. In the synthetic route, ring-closing metathesis was utilized for the construction of a butenolide moiety. A biological evaluation of the eight synthetic hybrid compounds revealed that these molecules exhibit antifouling activity against the cypris larvae of the barnacle Balanus (Amphibalanus) amphitrite with EC50 values of 0.30-1.31 μg mL-1. These results show that hybridization of the geraniol and butenolide structural motifs resulted in the enhancement of the antifouling activity.

DOI： 10.1039/c7ob01160a

Total Synthesis of Sarcophytonolide H and Isosarcophytonolide D: Structural Revision of Isosarcophytonolide D and Structure–Antifouling Activity Relationship of Sarcophytonolide H 査読

Hiroyoshi Takamura, Takahiro Kikuchi, Noriyuki Endo, Yuji Fukuda, Isao Kadota

Organic Letters 18 ( 9 ) 2110 - 2113 2016年5月

Chemical control of xylem differentiation by thermospermine, xylemin, and auxin 査読

Yoshimoto Kaori, Takamura Hiroyoshi, Kadota Isao, Motose Hiroyasu, Takahashi Taku

Scientific Reports 6 21487 - 21487 2016年2月

記述言語：英語出版者・発行元：Macmillan Publishers Limited.

The xylem conducts water and minerals from the root to the shoot and provides mechanical strength to the plant body. The vascular precursor cells of the procambium differentiate to form continuous vascular strands, from which xylem and phloem cells are generated in the proper spatiotemporal pattern. Procambium formation and xylem differentiation are directed by auxin. In angiosperms, thermospermine, a structural isomer of spermine, suppresses xylem differentiation by limiting auxin signalling. However, the process of auxin-inducible xylem differentiation has not been fully elucidated and remains difficult to manipulate. Here, we found that an antagonist of spermidine can act as an inhibitor of thermospermine biosynthesis and results in excessive xylem differentiation, which is a phenocopy of a thermospermine-deficient mutant acaulis5 in Arabidopsis thaliana. We named this compound xylemin owing to its xylem-inducing effect. Application of a combination of xylemin and thermospermine to wild-type seedlings negates the effect of xylemin, whereas co-treatment with xylemin and a synthetic proauxin, which undergoes hydrolysis to release active auxin, has a synergistic inductive effect on xylem differentiation. Thus, xylemin may serve as a useful transformative chemical tool not only for the study of thermospermine function in various plant species but also for the control of xylem induction and woody biomass production.

DOI： 10.1038/srep21487

Stereoselective Synthesis of the Proposed C79-C104 Fragment of Symbiodinolide

Hiroyoshi Takamura, Takayuki Fujiwara, Yohei Kawakubo, Isao Kadota, Daisuke Uemura

Chemistry - A European Journal 22 ( 6 ) 1979 - 1983 2016年2月

Inside Back Cover: Stereodivergent Synthesis and Stereochemical Reassignment of the C79-C104 Fragment of Symbiodinolide (Chem. Eur. J. 6/2016)

Hiroyoshi Takamura, Takayuki Fujiwara, Yohei Kawakubo, Isao Kadota, Daisuke Uemura

Chemistry - A European Journal 22 ( 6 ) 2183 - 2183 2016年2月

Stereodivergent Synthesis and Stereochemical Reassignment of the C79-C104 Fragment of Symbiodinolide

Hiroyoshi Takamura, Takayuki Fujiwara, Yohei Kawakubo, Isao Kadota, Daisuke Uemura

Chemistry - A European Journal 22 ( 6 ) 1984 - 1996 2016年2月

Convergent synthesis of the EFGH ring system of ciguatoxin CTX3C 査読

Isao Kadota, Yuki Sato, Naoya Fujita, Hiroyoshi Takamura, Yoshinori Yamamoto

TETRAHEDRON 71 ( 37 ) 6547 - 6558 2015年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

Convergent synthesis of the EFGH ring segment of ciguatoxin CTX3C was investigated by using the intramolecular allylation of an alpha-chloroacetoxy ether and/or O,S-acetal, and subsequent ring-closing metathesis. A new method for the preparation of gamma-alkoxyallylstannane is also described. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2015.04.106

Stereodivergent Synthesis and Relative Stereostructure of the C1–C13 Fragment of Symbiodinolide

Hiroyoshi Takamura, Hiroko Wada, Mao Ogino, Takahiro Kikuchi, Isao Kadota, Daisuke Uemura

The Journal of Organic Chemistry 80 ( 6 ) 3111 - 3123 2015年3月

STEREOCONTROLLED SYNTHESIS OF THE C1-C7 FRAGMENT OF ENIGMAZOLE A 査読

Takayuki Kishi, Yuka Fujisawa, Hiroyoshi Takamura, Isao Kadota

HETEROCYCLES 89 ( 2 ) 515 - 522 2014年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

An enantio- and stereoselective synthesis of the C1-C7 fragment of enigmazole A is described. The three asymmetric centers of the molecule were constructed efficiently by using Evans chiral auxiliary protocol.

DOI： 10.3987/COM-13-12905

IMPROVDED SYNTHESIS OF THE A-E RING SEGMENT OF CIGUATOXIN CTX3C 査読

Kengo Shiroma, Hiroki Asakura, Tokihiro Tanaka, Hiroyoshi Takamura, Isao Kadota

HETEROCYCLES 88 ( 2 ) 969 - 973 2014年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

The improved synthesis of the A-E ring segment of ciguatoxin CTX3C was performed via a highly convergent approach based on intramolecular allylation-RCM methodology.

DOI： 10.3987/COM-13-S(S)106

Stereoselective synthesis of the C79-C97 fragment of symbiodinolide

Hiroyoshi Takamura, Takayuki Fujiwara, Isao Kadota, Daisuke Uemura

BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY 9 1931 - 1935 2013年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BEILSTEIN-INSTITUT

Symbiodinolide is a polyol marine natural product with a molecular weight of 2860. Herein, a streamlined synthesis of the C79-C97 fragment of symbiodinolide is described. In the synthetic route, a spiroacetalization, a Julia-Kocienski olefination, and a Sharpless asymmetric dihydroxylation were utilized as the key transformations.

DOI： 10.3762/bjoc.9.228

Total synthesis, structural elucidation, and structure-cytotoxic activity relationship of (-)-gummiferol 査読

Takamura Hiroyoshi, Wada Hiroko, Lu Nan, Ohno Osamu, Suenaga Kiyotake, Kadota Isao

Journal of Organic Chemistry 78 ( 6 ) 2443 - 2454 2013年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

A highly stereoselective and stereodivergent synthesis of two possible diastereomers of (-)-gummiferol was achieved, wherein the stepwise epoxidation and Cadiot-Chodkiewicz reaction were utilized for the construction of the diepoxide moiety and triacetylene part, respectively. Detailed comparison of their 1H and 13C NMR data and specific rotation with those of the natural product unambiguously elucidated the absolute stereostructure of gummiferol. In addition, the cytotoxic activity of the synthesized gummiferol, its stereoisomers, and its truncated analogues was evaluated, which clearly indicates that (1) the absolute configuration of the diepoxide moiety has little influence on the cytotoxic activity against human cancer cells and (2) the triacetylene unit is the crucial structural element required for exerting the cytotoxic activity.

DOI： 10.1021/jo302665c

Total Synthesis of Two Possible Diastereomers of (+)-Sarcophytonolide C and Its Structural Elucidation

Hiroyoshi Takamura, Kohei Iwamoto, Eiji Nakao, Isao Kadota

ORGANIC LETTERS 15 ( 5 ) 1108 - 1111 2013年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER CHEMICAL SOC

Stereoselective and parallel total syntheses of two possible diastereomers of (+)-sarcophytonolide C have been accomplished. Macrolactonization and transannular ring-closing metathesis (RCM) were the key transformations. Detailed comparisons of their H-1 and C-13 NMR data and specific rotation with those of the natural product allowed the absolute configuration of (+)-sarcophytonolide C to be determined.

DOI： 10.1021/ol400157s

SYNTHESIS OF THE E RING SEGMENT OF CIGUATOXIN CTX3C VIA THE NEGISHI COUPLING OF CYCLIC KETENE ACETAL TRIFLATES 査読

Kengo Shiroma, Hiroyoshi Takamura, Isao Kadota

HETEROCYCLES 86 ( 2 ) 997 - 1001 2012年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

Stereocontrolled synthesis of the E ring segment of ciguatoxin CTX3C was performed via the Negishi coupling of cyclic ketene acetal triflates. Transformation of 8-membered lactones to the corresponding ketene acetal triflates was found to be affected by the protective groups of the substrates.

DOI： 10.3987/COM-12-S(N)117

Stereoselective synthesis of the C94-C104 fragment of symbiodinolide 査読

Hiroyoshi Takamura, Kosuke Tsuda, Yohei Kawakubo, Isao Kadota, Daisuke Uemura

Tetrahedron Letters 53 ( 33 ) 4317 - 4319 2012年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Stereoselective synthesis of the C94-C104 fragment of symbiodinolide which is a polyol marine natural product with a molecular weight of 2860 has been accomplished. The synthetic route features Achmatowicz rearrangement and RuO 4-catalyzed dihydroxylation for the construction of the tetrahydropyran moiety and the dithiane addition to the aldehyde for the introduction of the side chain. © 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2012.06.005

A convergent synthesis of the right-hand fragment of ciguatoxin CTX3C 査読

Hiroyoshi Takamura, Takashi Abe, Naoki Nishiuma, Rie Fujiwara, Takahiko Tsukeshiba, Isao Kadota

TETRAHEDRON 68 ( 10 ) 2245 - 2260 2012年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

A convergent synthesis of the right-hand fragment of ciguatoxin CTX3C was investigated. The first and second generation stereocontrolled syntheses of the LM ring fragment were achieved via spiroacetalization as a key step, respectively. The polyether framework of the HIJKLM ring fragment was constructed in a convergent manner by using intramolecular allylation, ring-closing metathesis, and stereoselective hydrogenation to form the 36-methyl substituent as the key transformations. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2012.01.071

Convergent Synthesis of the HIJKLM Ring System of Ciguatoxin CTX3C 査読

Hiroyoshi Takamura, Naoki Nishiuma, Takashi Abe, Isao Kadota

ORGANIC LETTERS 13 ( 17 ) 4704 - 4707 2011年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER CHEMICAL SOC

The HIJKLM ring system of ciguatozin CTX3C was synthesized in a convergent manner. The key steps were a conjugate addition/alkylation sequence, spiroacetalization, intramolecular allylation, ring-closing metathesis, and hydrogenation to form the 36-alpha-methyl substituent.

DOI： 10.1021/ol2019136

Total synthesis and absolute configuration of (-)-gummiferol 査読

Hiroyoshi Takamura, Hiroko Wada, Nan Lu, Isao Kadota

Organic Letters 13 ( 14 ) 3644 - 3647 2011年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Stereoselective synthesis of two possible diastereomers of (-)-gummiferol was accomplished by the stepwise epoxidation and Cadiot-Chodkiewicz reaction as the key transformations. Detailed comparison of their 1H and 13C NMR data and specific rotation with those of the natural product led to the absolute structural elucidation of (-)-gummiferol. © 2011 American Chemical Society.

DOI： 10.1021/ol201301b

Stereocontrolled synthesis and structural confirmation of the C14 - C24 degraded fragment of symbiodinolide 査読

Hiroyoshi Takamura, Yuichiro Kadonaga, Isao Kadota, Daisuke Uemura

Tetrahedron 66 ( 38 ) 7569 - 7576 2010年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The C14-C24 fragment of symbiodinolide possessing the 17R/18R/21R absolute configuration, which was obtained as one of the degraded products of symbiodinolide, and its diastereomer possessing the 17R/18S/21R absolute stereochemistry were synthesized stereoselectively from cis-2-butene-1,4-diol, respectively. The detailed comparison of the synthetic products with the degraded product in the spectroscopic data confirmed unambiguously that the stereostructure of the C14 - C24 fragment was 17R, 18R, and 21R. © 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2010.07.045

A new method for the stereoselective construction of angular methyl group of fuzed cyclic ethers 査読

Isao Kadota, Takayuki Kishi, Yuka Fujisawa, Yuji Yamagami, Hiroyoshi Takamura

TETRAHEDRON LETTERS 51 ( 30 ) 3960 - 3961 2010年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

A convenient method for the stereoselective construction of angular methyl group of fuzed cyclic ethers is described. Reactions of mixed thioacetals with Me(2)Zn/Zn(OTO)(2) afforded the corresponding methylated products in good yields. Various protective groups such as MOM ether, benzylidene acetal, TBS ether, and pivaloyl group were stable under the reaction conditions. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2010.05.109

Total synthesis of brevenal 査読

Hiroyoshi Takamura, Yuji Yamagami, Takayuki Kishi, Shigetoshi Kikuchi, Yuichi Nakamura, Isao Kadota, Yoshinori Yamamoto

TETRAHEDRON 66 ( 29 ) 5329 - 5344 2010年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

The convergent total synthesis of brevenal, a non-toxic brevetoxin antagonist, has been achieved. The ABC ring segment and the E ring precursor were connected by the intramolecular allylation followed by ring-closing metathesis to furnish the pentacyclic ether compound. An alternative route to the key synthetic intermediate, a pentacyclic ether core, was also examined. The right- and left-hand side chains were introduced by Wittig and Horner-Wadsworth-Emmons reactions, respectively, to furnish brevenal (1). (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2010.05.069

Stereoselective synthesis of the C14-C24 degraded fragment of symbiodinolide 査読

Hiroyoshi Takamura, Yuichiro Kadonaga, Isao Kadota, Daisuke Uemura

TETRAHEDRON LETTERS 51 ( 19 ) 2603 - 2605 2010年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

Symbiodinolide is a polyol macrolide isolated from the marine dinoflagellate Symbiodinium sp. in 2007. The C14-C24 fragment of symbiodinolide possessing the 17R/18R/21R absolute configuration, which was obtained as one of the degraded products of symbiodinolide, was synthesized stereoselectively from cis-2-butene-1,4-diol. The detailed comparison of the synthetic product with the degraded product in the spectroscopic data confirmed that the stereostructure of the C14-C24 fragment was 17R, 18R, and 21R. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2010.03.014

38 ブレベナールの全合成(口頭発表の部)

山神雄司, 菊池重俊, 中村祐一, 岸敬之, 高村浩由, 門田功, 山本嘉則

天然有機化合物討論会講演要旨集 ( 51 ) 223 - 228 2009年9月

記述言語：日本語出版者・発行元：天然有機化合物討論会

Brevenal (1), a new family of marine polycyclic ether, was isolated from the Florida red tide dinoflagellate Karenia brevis by Baden and co-workers in 2004. This compound inhibits the binding of tritiated dihydrobrebetoxin-B to the voltage-sensitive sodium channels in a concentration dependent manner and acts as a nontoxic brevetoxin antagonist. Moreover, a significiant improvement of tracheal mucus velocity was observed in an animal model asthma. As well as the novel biological activities, the unique structural features have attracted attention of synthetic chemists. In 2006, the first total synthesis and structure revision of 1 were reported by Sasaki and co-workers. In this paper, we wish to report eht recent results and our efforts on the total synthesis of brevenal (1). The ABC ring segment 3 was prepared from the known compound 7 the B-alkyl Suzuki-Miyahara coupling of the phosphate 11 and the alkylborate from the iodine 5. Direct methylation of the O,S-acetal 16 was performed by using Me_2Zn/Zn(OTf)_2 in highly stereoselective manner. The ABC ring fragment obtained and the known alchol 4 were connected by our own synthetic strategy including the intramolecular allylation of α-acetoxy ether followed by ring-closing metathesis to furnish the pentacyclic ether 2. The right hand diene was introduced by the Nicolaoua's protocol. Construction of the left hand side chain, highly substituted dienyl moiety, was archieved by the modified Horner-Wadsworth-Emmons reaction with the phosphonate 33, newly developed, to afford the dienyl ether 34 as the sole product. A seris of functional transformation and deprotections of 34 furnished brevenal (1). The synthetic 1 exhiibited physical and spectroscopic data identical to those reported previously.

DOI： 10.24496/tennenyuki.51.0_223

Stereoselective synthesis and absolute configuration of the C33-C42 fragment of symbiodinolide 査読

Hiroyoshi Takamura, Yuichiro Kadonaga, Yoshi Yamano, Chunguang Han, Isao Kadota, Daisuke Uemura

TETRAHEDRON 65 ( 36 ) 7449 - 7456 2009年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

Cross-metathesis of methyl ester which was prepared from symbiodinolide with ethylene was performed to give the C33-C42 degraded fragment. This fragment was estimated to be (36S,40S)-diol by the modified Mosher method. Stereoselective synthesis of the (36S,40S)-diol and its diastereomer (36R,40S)-diol was achieved from L-aspartic acid. Synthetic bis-(S)- and (R)-MTPA esters which were derivatized from the (36S,40S)-diol exhibited spectroscopic data identical with those of bis-(S)- and (R)-MTPA esters derived from the degraded product. Thus, the absolute stereochemistry of the C33-C42 fragment was elucidated to be (36S,40S). (C) 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2009.07.019

Stereoselective Synthesis and Absolute Configuration of the C1 '-C25 ' Fragment of Symbiodinolide 査読

Hiroyoshi Takamura, Takeshi Murata, Takahiro Asai, Isao Kadota, Daisuke Uemura

JOURNAL OF ORGANIC CHEMISTRY 74 ( 17 ) 6658 - 6666 2009年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER CHEMICAL SOC

Stereoselective synthesis of the C1'-C25' fragment of symbiodinolide, which was obtained as a degraded product from symbiodinolide by alkaline hydrolysis, has been accomplished. The synthetic route features Kotsuki coupling and Julia-Kocienski olefination in the introduction of the side chains. This enantio-and stereoselective synthesis has established the absolute configuration of the C1'-C25' fragment.

DOI： 10.1021/jo901162v

Convergent synthesis of the A-E ring segment of ciguatoxin CTX3C 査読

Isao Kadota, Takashi Abe, Miyuki Uni, Hiroyoshi Takamura, Yoshinori Yamamoto

TETRAHEDRON 65 ( 37 ) 7784 - 7789 2009年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

A convergent synthesis of the A-E ring segment of ciguatoxin CTX3C was achieved via the intramolecular allylation of an alpha-chloroacetoxy ether and subsequent ring-closing metathesis. (C) 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2009.07.037

Selective cleavage of primary MPM ethers with TMSI/Et3N 査読

Isao Kadota, Yuji Yamagami, Naoya Fujita, Hiroyoshi Takamura

TETRAHEDRON LETTERS 50 ( 31 ) 4552 - 4553 2009年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

A useful method for the selective cleavage of primary MPM ethers by using TMSI/Et3N is described. Other protective groups such as secondary MPM ethers, silyl ethers, and benzylidene acetal were stable under the reaction conditions. (C) 2009 Elsevier Ltd. Ail rights reserved.

DOI： 10.1016/j.tetlet.2009.05.084

Synthesis and structural revision of symbiodinolide C23-C34 fragment 査読

Takeshi Murata, Masayuki Sano, Hiroyoshi Takamura, Isao Kadota, Daisuke Uemura

Journal of Organic Chemistry 74 ( 13 ) 4797 - 4803 2009年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

(Chemical Equation Presented) Stereoselective synthesis of the C23-C34 fragment of symbiodinolide, which possesses the originally proposed stereochemistry, and its diastereomers was achieved in 19 steps from L-aspartic acid, respectively. Comparison of spectroscopic data of the synthetic products with those of the degraded product of symbiodinolide led to a structural revision of the C23-C34 fragment. © 2009 American Chemical Society.

DOI： 10.1021/jo900546k

Total Synthesis of Brevenal 査読

Hiroyoshi Takamura, Shigetoshi Kikuchi, Yuichi Nakamura, Yuji Yamagami, Takayuki Kishi, Isao Kadota, Yoshinori Yamamoto

ORGANIC LETTERS 11 ( 12 ) 2531 - 2534 2009年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER CHEMICAL SOC

A total synthesis of brevenal is described. The pentacyclic ether core was constructed by the intramolecular allylation of alpha-acetoxy ether and subsequent ring-closing metathesis. Both of the diene side chains were introduced by Wittig olefination and a Horner-Wadsworth-Emmons reaction, respectively, in a highly stereoselective manner.

DOI： 10.1021/ol900769d

Synthesis and structural determination of the C33-C42 fragment of symbiodinolide 査読

Hiroyoshi Takamura, Yuichiro Kadonaga, Yoshi Yamano, Chunguang Han, Yoko Aoyama, Isao Kadota, Daisuke Uemura

Tetrahedron Letters 50 ( 8 ) 863 - 866 2009年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Symbiodinolide (1) is a polyol macrolide with a molecular weight of 2859 mu. As one of the degradation reactions, cross-metathesis of 2, which is a methyl ester of 1, with ethylene was performed to give the C33-C42 degraded fragment 4. The absolute configuration of 4 was estimated to be (36S,40S) by Mosher method. Stereoselective synthesis of 4 was achieved in 14 steps from l-aspartic acid. Synthetic bis-(S)- and (R)-MTPA esters exhibited the spectroscopic data identical with those of bis-(S)- and (R)-MTPA esters derived from the degraded fragment 4. Thus, the absolute stereochemistry of 4 was elucidated to be (36S,40S). © 2009.

DOI： 10.1016/j.tetlet.2008.11.056

A TRANSANNULAR DIELS-ALDER STRATEGY TO THE CONSTRUCTION OF THE CDE RING SYSTEM OF NAKITERPIOSIN 査読

Hiroyoshi Takamura, Yuji Yamagami, Tomonori Ito, Masahiro Ito, Hirokazu Arimoto, Isao Kadota, Daisuke Uemura

HETEROCYCLES 77 ( 1 ) 351 - 364 2009年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

The transannular Diels-Alder (TADA) reaction was applied to the synthesis of the CDE ring system of nakiterpiosin (1). TADA product 28 is a key intermediate toward the total synthesis of 1.

DOI： 10.3987/COM-08-S(F)26

Stereocontrolled synthesis of the C79-C96 fragment of symbiodinolide 査読

Hiroyoshi Takamura, Junki Ando, Takashi Abe, Takeshi Murata, Isao Kadota, Daisuke Uemura

TETRAHEDRON LETTERS 49 ( 31 ) 4626 - 4629 2008年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

DOI： 10.1016/j.tetlet.2008.05.078

A cross-metathesis approach to the stereocontrolled synthesis of the AB ring segment of ciguatoxin 査読

Isao Kadota, Takashi Abe, Miyuki Uni, Hiroyoshi Takamura, Yoshinori Yamamoto

TETRAHEDRON LETTERS 49 ( 22 ) 3643 - 3647 2008年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

Synthesis of the AB ring segments of ciguatoxin is described. The present synthesis includes a Lewis acid mediated cyclization of allylstannane with aldehyde, cross-metathesis reaction introducing the side chain, and Grieco-Nishizawa dehydration on the A ring. (C) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2008.03.145

Solvent-controlled stereoselective formation of a cyclic ether in the lewis acid-mediated allylation of an alpha-Chloroacetoxy acyclic ether. Very high stereoselectivity in CH3CN vs low stereoselectivity in CH2Cl2 査読

Ilya D. Gridnev, Shigetoshi Kikuchi, Abeda S. Touchy, Isao Kadota, Yoshinori Yamamoto

JOURNAL OF ORGANIC CHEMISTRY 72 ( 22 ) 8371 - 8375 2007年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER CHEMICAL SOC

The MgBr2-OEt2-mediated intramolecular allylation of a 4:1 diastereoisomeric mixture of the alpha-chloroacetoxyl ether la bearing the A-G/JK ring system of brevetoxin B in CH2Cl2 gave a 1: 1 diastereoisomeric mixture of the trans- and cis-cyclization products 4a and 5a having the A-G/I-K ring system, while that in CH3CN afforded the trans-isomer 4a nearly as the single product. To help clarify a reason for this marked solvent effect in the cyclization of the brevetoxin B precursor, DFT computations for the starting materials, intermediates, transition states, and products were carried out. The cyclization would proceed through a carbocation intermediate 3a having sp(2) flat structure (S(N)1 type mechanism) in CH2Cl2, in which the activation energies leading to both diastereoisomers are approximately identical, while in CH3CN alkylnitrilium salts 6a would be formed through the coordination of CH3CN to the carbocation leading to an sp(3)-type intermediate in which sever steric hindrance takes place in the transition state leading to the undesired diastereoisomer. The scope of this novel solvent-controlled stereo selectivity was tested for simple compounds. In small model compounds the marked solvent dependence was absent, but the model bearing two consecutive cyclic ether rings 1b exhibited a remarkable solvent effect similar to that observed in the brevetoxin B system.

DOI： 10.1021/jo701352

A convergent approach to the formal total synthesis of hemibrevetoxin B 査読

Isao Kadota, Takashi Abe, Yukako Ishitsuka, Abeda S. Touchy, Ryoko Nagata, Yoshinori Yamamoto

TETRAHEDRON LETTERS 48 ( 2 ) 219 - 221 2007年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

A convergent synthesis of the key synthetic intermediate of hemibrevetoxin B was achieved via the intramolecular allylation of an alpha-chloroacetoxy ether and subsequent ring-closing metathesis. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2006.11.058

Formal total synthesis of hemibrevetoxin B via the intramolecular allylation followed by ring-closing metathesis 査読

Isao Kadota, Takashi Abe, Yukako Ishitsuka, Abeda S. Touch, Ryoko Nagata, Yoshinori Yamamoto

HETEROCYCLES 74 617 - 627 2007年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

A formal total synthesis of hemibrevetoxin B (1) is described. Intramolecular allylation of alpha-chloroacetoxy ether 10, prepared from carboxylic acid 11 and alcohol 12, was carried out with MgBr2 center dot OEt2 to give 27. Ring-closing metathesis of 27 furnished tetracycle 29, which was converted to a known synthetic intermediate 9, to complete a formal total synthesis of 1.

DOI： 10.3987/COM-07-S(W)39

Stereocontrolled synthesis of the IJK ring segment of yessotoxin 査読

Isao Kadota, Takashi Abe, Yuki Sato, Chizuko Kabuto, Yoshinori Yamamoto

TETRAHEDRON LETTERS 47 ( 37 ) 6545 - 6548 2006年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

A stereocontrolled synthesis of the IJK ring segment of yessotoxin is described. Cyclization of 11 mediated by SmI2 gave the IJ ring system 12 as the sole product. Construction of the K ring moiety was performed by the acid catalyzed cyclization of epoxy alcohol 20 to afford the IJK ring segment in a highly stereocontrolled manner. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2006.07.027

P-141 Convergent Synthesis of Hemibrevetoxin B

Ishitsuka Yukako, Abeda Touchy, Nagata Ryoko, Kadota Isao, Yamamoto Yoshinori

International Symposium on the Chemistry of Natural Products 2006 "P - 141" 2006年7月

P-140 Synthesis of the IJK Ring Segment of Yessotoxin

Abe Takashi, Sato Yuki, Kadota Isao, Yamamoto Yoshinori

International Symposium on the Chemistry of Natural Products 2006 "P - 140" 2006年7月

Improved synthesis of the A-G ring segment of brevetoxin B 査読

Isao Kadota, Hiroki Nishii, Hiroki Ishioka, Hiroyoshi Takamura, Yoshinori Yamamoto

JOURNAL OF ORGANIC CHEMISTRY 71 ( 11 ) 4183 - 4187 2006年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER CHEMICAL SOC

An efficient synthesis of the A-G ring segment 2, a key intermediate for the total synthesis of brevetoxin B (1), was achieved in 37 steps and 5.0% overall yield. The intramolecular allylation of the O,S-acetal 22, prepared from the ABC ring segment 15 and the FG ring segment 17, was carried out using AgOTf as a Lewis acid to give the desired compound 23, predominantly. Ring-closing metathesis of 23 with the Grubbs catalyst 12 afforded the heptacyclic ether 25. Selective hydrogenation of the E ring olefin of 25 was performed by diimide reduction to afford 2.

DOI： 10.1021/jo0603025

Convergent synthesis of the FGHI ring segment of yessotoxin 査読

Isao Kadota, Hirokazu Ueno, Yuki Sato, Yoshinori Yamamoto

Tetrahedron Letters 47 ( 1 ) 89 - 92 2006年1月

P-31 ブレベトキシンBの全合成(ポスター発表の部)

高村浩由, 西井広樹, 石岡裕貴, 門田功, 山本嘉則

天然有機化合物討論会講演要旨集 ( 47 ) 325 - 330 2005年9月

記述言語：日本語出版者・発行元：天然有機化合物討論会

Brevetoxin B (1), a potent neurotoxin, was isolated from the red tide organism Gymnodinium breve Davis in 1981. The unique structural features and biological activity of this molecule have attracted the attention of synthetic chemists. We have already reported the efficient method for the convergent synthesis of polycyclic ethers via the intramolecular allylation and subsequent ring-closing metathesis. Herein we report the convergent total synthesis of 1 based on our own methodology. The reaction of the bicyclic compound 9, prepared from the known compound 6, with the allylic silane 10 in the presence of TMSOTf gave the desired product 11, stereoselectively. The JK ring segment 3 was synthesized in 11 steps including one-carbon elongation from 11. Palladium-catalyzed coupling of the ketene acetal triflate 15 and the organozinc reagent 16 gave the enol ether 17, which was converted to the diene 22. The construction of the A ring via ring-closing metathesis afforded the ABC ring segment 4. The chlorosulfide 4 was treated with the alcohol 5 in the presence of AgOTf and DTBMP to give the O,S-acetal 24. Intramolecular allylation of 26 using AgOTf as a Lewis acid provided the desired product 27, stereoselectively. Chemoselective reduction of the olefinic moiety in the E ring of 29 was carried out under the condition of the diimide reduction to afford 30. The heptacyclic compound 30 was converted to the alcohol 2 in 6 steps including one-carbon elongation. The alcohol 2 and the carboxylic acid 3 were connected successfully by Yamaguchi conditions to give the ester 33. The construction of the polycyclic framework of 1 was performed via the intramolecular allylation and subsequent ring-closing metathesis to yield 38. After the TBS and TBDPS protecting groups were removed using HF・pyr, chemoselective oxidation of the allylic moiety with MnO_2 furnished brevetoxin B (1). The synthetic brevetoxin B exhibited spectroscopic data identical with those of natural brevetoxin B.

DOI： 10.24496/tennenyuki.47.0_325

Total synthesis of brevetoxin B 査読

Kadota, I, H Takamura, H Nishii, Y Yamamoto

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 127 ( 25 ) 9246 - 9250 2005年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER CHEMICAL SOC

The convergent total synthesis of brevetoxin B (1) has been achieved. The intramolecular allylation of the 0,S-acetal 20, prepared from the alpha-chlorosulfide 17 and the alcohol 5, was carried out using AgOTf as a Lewis acid to give the diene 21, predominantly. Ring-closing metathesis of 21 with the Grubbs catalyst 23 afforded the hexacyclic ether 25 which was converted to the A-G ring segment 2 through several steps. The intramolecular allylation of the alpha-acetoxy ether 42, prepared from 2 and the J-K ring segment 3, followed by ring-closing metathesis provided the polycyclic ether framework 44. A series of reactions of 44, including oxidation of the A ring, deprotection of the silyl ethers, and selective oxidation of the resulting allylic alcohol, furnished 1.

DOI： 10.1021/ja051171c

A convenient and efficient route for the allylation of aromatic amines and alpha-aryl aldehydes with alkynes in the presence of a Pd(O)/PhCOOH combined catalyst system 査読

NT Patil, HY Wu, Kadota, I, Y Yamamoto

JOURNAL OF ORGANIC CHEMISTRY 69 ( 25 ) 8745 - 8750 2004年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER CHEMICAL SOC

The allylation of aromatic amines with alkynes proceeded smoothly in the presence of catalytic amounts of Pd(PPh3)(4) and benzoic acid. The allylation products were obtained in high yields in a regio- and stereoselective manner. The effect of various groups on the nitrogen atom of anilines was studied. Regardless of the substituent (electron withdrawing or electron donating) on the aromatic ring, the reaction proceeded well. Various functionalities, including -CH3, -OMe, -Cl, -CN, -COOMe, -NO2 and -COCH3 were tolerated under the reaction conditions. Similarly, the allylation of alpha-aryl aldehydes proceeded well with the same level of regio- and stereoselectivity as the allylation of aromatic amines. This reaction provides the second example of the transition metal catalyzed direct alpha-allylation of aldehydes.

DOI： 10.1021/jo0485684

37(D-7) ブレベトキシンBの合成研究(口頭発表の部)

高村浩由, 西井広樹, 門田功, 山本嘉則

天然有機化合物討論会講演要旨集 ( 46 ) 197 - 202 2004年10月

記述言語：日本語出版者・発行元：天然有機化合物討論会

Brevetoxin B (1), a potent neurotoxin was isolated from the red tide organism Gymnodinium breve Davis in 1981. The unique structural features and biological activity of this molecule have attracted the attention of synthetic chemists. We have already reported the efficient method for the convergent synthesis of polycyclic ethers via the intramolecular allylation and subsequent ring-closing metathesis. Herein we report the convergent synthesis of the polycyclic framework of 1 based on our own methodology. The reaction of the bicyclic compound 12, prepared from the known compound 9, with the allylic silane 13 in the presence of TMSOTf gave the desired product 14, stereoselectively. The JK ring segment 6 was synthesized in 11 steps including one-carbon elongation from 14. Palladium-catalyzed coupling of the ketene acetal triflate 22, prepared from the known compound 18, and the organozinc reagent 23 gave the enol ether 24, which was converted to the BC ring segment 7. The connection of 7 and the FG ring segment 8 followed by several transformations afforded the allylic stannane 29. The partial reduction of 29 with DIBALH followed by trapping of the resulting aluminum hemiacetal with acetic anhydride provided the acetoxy ether 30. However, the yield was very low. Alternatively, the chlorosulfide 31, prepared from 26, was treated with the alcohol 8 in the presence of AgOTf to provide the O,S-acetal 32. Cyclization of 33 using AgOTf as a Lewis acid gave the desired product 34, stereoselectively. The construction of the E ring and the A ring via ring-closing metathesis afforded the ABCDEFG ring segment 5. The alcohol 5 and the carboxylic acid 6 were connected successfully by Yamaguchi conditions to give the ester 41. The construction of the polycyclic framework of 1 was performed via the intramolecular allylation and subsequent ring-closing metathesis to yield 46. Completion of the total synthesis of 1 is currently under way.

DOI： 10.24496/tennenyuki.46.0_197

26 ガンビエロールの合成研究(口頭発表の部)

高村浩由, 大野昭男, 佐藤公美, 松田久美子, 山本嘉則, 門田功

天然有機化合物討論会講演要旨集 ( 44 ) 151 - 156 2002年9月

記述言語：日本語出版者・発行元：天然有機化合物討論会

Gambierol (1) is a marine polycyclic ether isolated as a toxic constituent from cultured cells of the ciguatera causative dinoflagellate, Gambierdiscus toxicus. This compound shows toxicity against mice (LD_<50>, 50μg/kg), and the symptoms resemble those caused by ciguatoxins. The unique structural features have attracted the attention of synthetic chemist. We have already succeeded in the convergent synthesis of the CDEFG ring system (8) via the intramolecular allylation of the α-acetoxy ether 4 and subsequent ring-closing metathesis. Encouraged by this result, we started the total synthetic study of gambierol (1). Treatment of the cyclization precursor 15, prepared from the ABC ring segment 10 and FGH ring fragment 11, with MgBr_2・OEt_2 gave the desired product 9 and its C16 epimer 16 in 22% and 47% yield, respectively. The yield of 9 was improved by using monochloroacetoxy group as a leaving moiety. Thus, the reaction of 19 gave 9 and 16 in 30% and 48% yield, respectively. The diene 9 was subjected to ring-closing metathesis with 7 to give 20 in 84% yield. The octacyclic compound 20 was converted to 28 by several steps. We next examined the construction of the triene side chain. Although the Stille coupling of 29 and 30 gave the cross-coupling product 31 in an allowable yield (63%), the reaction was very slow (4 days). After unfruitful attempts, we succeeded in developping an efficient method for the stereoselective synthesis of Z-iodoolefin 33. Treatment of 32 with Zn-Cu and AcOH gave 33 as a single stereoisomer in 80% yield. As expected, the reaction of 33 and 30 was very fast. The triene 31 was obtained in 95% yield after 1.5h. Similaly, the iodoolefin 35, prepared from 28, was converted to the fully protected gambierol 36 in good yield. The final deprotection of 36 giving 1 is currently under way.

DOI： 10.24496/tennenyuki.44.0_151

41 ポリ環状エーテルの収束的合成とガンビエロール全合成への応用(口頭発表の部)

門田功, 大野昭男, 高村浩由, 佐藤公美, 松田久美子, 山本嘉則

天然有機化合物討論会講演要旨集 ( 43 ) 241 - 246 2001年9月

記述言語：日本語出版者・発行元：天然有機化合物討論会

A convergent synthesis of polycyclic ethers has been achieved by the intramolecular allylation of α-acetoxy ethers and subsequent ring-closing metathesis. The carboxylic acid 2 and alcohol 3 were connected by DCC coupling to give the ester 4 in 90% yield. After deprotection of the silyloxy group, the alcohol 5 was converted to the allylic stannane 8 via the mixed acetal 7 in good yield. The ester 8 was then subjected to the Rychnovsky protocol to give the α-acetoxy ether 9 as a mixture of diastereoisomers. The cyclization precursors 10-15 were prepared in a similar manner, and the results of the cyclization are summarized in Table 1. Treatment of 9 with 4 equiv of BF_3・OEt_2 gave a 70: 30 mixture of the cyclized products 16 and 17 in 79% yield (entry 1). Similarly, the cyclization of the substrates 10-15 proceeded stereoselectively to give the desired products in good yields (entries 2-7). We next examined the ring-closing metathesis of the products 18, 20, 22, 24, 25, and 27 (Table 2). Treatment of 18 with Grubbs catalyst 29 gave the tetracyclic ether 30 in 91% yield (entry 1). Similarly, the reactions of 20, 22, and 24 proceeded smoothly to afford the corresponding polycyclic ethers 31-33 in good yields (entries 2-4). Although the reactions of 25 and 27 with 29 were unsatisfactory, the use of the more active catalyst 34 provided the desired pentacyclic ethers 35 and 36 in high yield (entries 5 and 6). Based on these results, we have started the convergent synthesis of gambierol 1 and have synthesized the ABC and FGH ring segments, 48 and 60, from 2-deoxy-D-robose as shown in Schemes 2 and 3, respectively. Further studies toward the total synthesis of gambierol are now in progress in our laboratories.

DOI： 10.24496/tennenyuki.43.0_241

38 Gambierolの合成研究(口頭発表の部)

門田功, 門脇千恵, 朴哲弘, 大野昭男, 大高学, 小黒奈央, 山本嘉則

天然有機化合物討論会講演要旨集 ( 40 ) 223 - 228 1998年8月

記述言語：日本語出版者・発行元：天然有機化合物討論会

Since 1981, a number of polycyclic ethers have been isolated from marine dinoflagellates. Much attention has been paid to the synthesis of these compounds due to their unusual structures, biological activities, and the rarity in nature. Gambierol, which has a 6,6,6,6,7,6,6,7-polycyclic ether skeleton including 18 stereocenters and a triene side chain, was isolated from the cultured cells of Gambierdiscus toxicus by Yasumoto in 1993. The compound shows toxicity against mice (LD_<50> 50μg/kg), and the symptoms resemble those caused by ciguatoxins inferring the possibility that it is also implicated in ciguatera poisoning. We now report the stereocontrolled construction of the AB, E, and H ring systems of Gambierol as parts of its total synthetic study. First, synthesis of the AB ring system of gambierol was achieved from 2-deoxy-D-ribose. The key steps were the stereoselective allylation of the aldehyde 2, corresponding to the B ring, and the intramolecular hetero-Michael reaction of 5. Next, the synthesis of the E ring was accomplished from D-ribose via the intramolecular reaction of allylic stannane 24 as a key step. The undesired stereoisomer 26 formed in this reaction was converted to the desired product 33 by using DBU mediated isomerization. Finally, stereoselective synthesis of the H ring was achieved from 2-deoxy-D-ribose by using the intramolecular reaction of allylic stannane 43 as a key step. Modified Stille coupling was successfully applied for the construction of the triene side chain to give 57.

DOI： 10.24496/tennenyuki.40.0_223

119(P62) ポリ環状エーテルの立体選択的合成とその応用(ポスター発表の部)

門田功, 朴正烈, 佐谷志保子, 川田美穂, 山本嘉則

天然有機化合物討論会講演要旨集 ( 38 ) 709 - 714 1996年9月

記述言語：日本語出版者・発行元：天然有機化合物討論会

The synthetic reaction using functionalized allylstannanes is widely appreciated as one of the most useful methods for the stereocontrolled C-C bond formation. We now report the stereoselective synthesis of functionalized heterocycles via the intramolecular reaction of allylstannane with aldehyde and imine. Stereocontrolled Total Synthesis of Hemibrevetoxin B The treatment of 6 with BF_3・OEt_2 gave 7 as a sole product. Similarly, the intramolecular reaction of 13 derived from 7 proceeded smoothly to give 14. The obtained tetracycle 14 was transformed to hemibrevetoxin B (1) by several steps. Intramolecular Reaction of Imine Derivatives To extend our methodology, we next examined the intramolecular reaction with imine, because the allylation of imine has been well studied as well as that of aldehyde, and such transformation would be an efficient method for the synthesis of cyclic amine derivatives. After several fruitless attempts, we found hydrazones are suitable as a carbon-nitrogen double bond functional group for the intramolecular reaction. The Lewis acid mediated reactions of 16 and 17 gave trans isomers 18a and 19a as a sole product in high to good yields. Stereoselective Synthesis of Hydroxylated Piperidine and Pyrrolidine Derivatives The structural framework of hydroxylated nitrogen heterocycle is widely found in naturally occurring piperidine/pyrrolidine alkaloids such as (-)-desoxoprosophilline and (+)-preussin. We examined the stereoselective synthesis of β-hydroxypiperidine and pyrrolidine derivatives via the intramolecular reaction of 20 and 22. To the best of our knowledge, this is the first example of a successful use of γ-aminoallylstannane in organic synthesis.

DOI： 10.24496/tennenyuki.38.0_709

Total synthesis of hemibrevetoxin B via the allylic tin methodology

Isao Kadota, Yoshinori Yamamoto

Main Group Metal Chemistry 19 ( 6 ) 361 - 366 1996年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Walter de Gruyter GmbH

The total synthesis of Hemibrevetoxin B is described. A new cyclization approach, based on the Lewis acid mediated intramolecular cyclization of the γ-oxo-substituted allylic tin having an aldehyde group, produced the 6-6-7-7 polycyclic ether skeleton of the natural product with high stereoselectivity. The 1H and 13C-NMR spectra of synthetic hemibrevetoxin B was identical with those of natural product.

DOI： 10.1515/MGMC.1996.19.6.361

24 ヘミブレベトキシンBの全合成(口頭発表の部)

門田功, 山本嘉則

天然有機化合物討論会講演要旨集 ( 37 ) 139 - 143 1995年9月

記述言語：日本語出版者・発行元：天然有機化合物討論会

Hemibrevetoxin B (1), isolated from cultured cells of the red tide organism Gymnodinium breve by Prasad and Shimizu in 1989, has a 6,6,7,7-tetracyclic ether skeleton and contains 10 stereocenters. Much attention has been paid to the synthesis of polycyclic ethers including hemibrevetoxin B owing to their unusual structural framework, novel functionalities, and biological activities. Recently, Nicolaou and coworkers have reported the first total synthesis of hemibrevetoxin B. We have reported stereocontrolled synthesis of the 6,6,7,7-tetracyclic ether skeleton of 1 via the intramolecular allylic tin-aldehyde (and ketone) condensation. Chain elongation to the left-hand side aldehyde from this intermediate was difficult, and therefore we utilized 2 having hydroxypropyl side chain as a starting material. The total synthesis of 1 has been accomplished via the allylic tin methodology. The 6,6-ring system 11 prepared via the modified Nicolaou method was converted to 18. Cyclization of 18 with BF_3・OEt_2, proceeded quite smoothly and stereoselectively to give 19 in 94% yield. No diastereoisomers were detected in the cyclization step. The BF_3・OEt_2 mediated cyclization of 25 prepared from 19 by usual transformation provided the 6,6,7,7 system 26 as a single stereoisomer. Oxidation followed by Grignard reaction gave methyl carbinol derivative as a 1:1 mixture of diasteroisomers. After silyl protection, the desired isomer 27 was isolated by column chromatography. Diene side chain was introduced by Wittig olefination followed by elimination to give 30. Construction of the α-methylene aldehyde moiety was achieved by Mannich reaction with Eschenmoser's salt. ^1H and ^<13>C-NMR spectra of synthetic hemibrevetoxin B(1) was identical with those of natural product.

DOI： 10.24496/tennenyuki.37.0_139

11 14族有機金属化合物を用いる新規環化反応の開発とポリエーテル系天然物合成への応用(口頭発表の部)

門田功, Gevorgan V., 山田順一, 山本嘉則

天然有機化合物討論会講演要旨集 ( 33 ) 78 - 85 1991年9月

記述言語：日本語出版者・発行元：天然有機化合物討論会

Recently, we have developed a novel and efficient method for the synthesis of β-alkoxy cyclic ethers. This methodology is based on the intramolecular reaction of the group 14 organometallics with acetals or aldehydes. Thus, treatment of γ-alkoxyallylsilane 1 with TiCl_4-PPh_3 afforded 6-membered cyclic ether 2a as a major product along with small amounts of its cis isomer 2b (95% total yield, trans:cis=98:2). Furthermore, this cyclization reaction was applicable for the synthesis of 7- and 8- membered cyclic ethers (Table II, Scheme 1). As a next stage, we carried out the construction of 6-7-7-6 fuzed ring system 16 which is the CDEF ring skeleton of brevetoxin B(Scheme 2, 3, 4). The BF_3・OEt_2 promoted reaction of 23 derived from optically active diol 17 gave 24 in 99% yield without accompaning the formation of any other stereoisomers. The most attractive aspect of the present procedure was iterative ring construction; the repeated use of the allic tin based cyclization gave 16 in good yield.

DOI： 10.24496/tennenyuki.33.0_78

64(P1-12) キラルなトリフレート誘導体を用いる光学活性天然物の合成(ポスター発表の部)

小槻日吉三, 門田功, 越智雅光

天然有機化合物討論会講演要旨集 ( 31 ) 490 - 497 1989年9月

記述言語：日本語出版者・発行元：天然有機化合物討論会

Recently, we have developed a new and efficient method for the carbon-carbon bond forming reaction by using copper(I)-catalyzed Grignard reagents with triflates, which bear a β-oxygen fuctionality. Since those starting triflates are readily accessible from simple chiral building blocks, the procedure provides a very convenient approach to synthesize a variety of natural products in optically active forms. As an application of this methodology, we have accomplished the enantioselective syntheses of (+)-exo-brevicomin (7), one of the aggregation pheromones of bark beetles, and (5R,6S)-(-)-6-acetoxy-5-hexadecanolide (16), a major oviposition attractant pheromone of the mosquito Culex pipiens fatigans, via tosyl-triflate 6 as a common key intermediate. In both examples the use of 6 has enabled us to realize the sequential C-C bond formation in one-pot operation and hence the overall yields were considerably improved. The similar strategy could be applied to the synthesis of naturally occurring hydroxy-γ-lactone 12 (termed L-factor). As an alternative pathway, the stepwise methods towards these target molecules were also examined.

DOI： 10.24496/tennenyuki.31.0_490