著者

森本 俊明 阿知波 一雄 千葉 三男

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 31 (ISSN:24331856)

巻号頁・発行日

pp.183-189, 1989-09-17 (Released:2017-08-18)

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We found that neutral and cationic rhodium (I) complexes of (S,S)- or (R,R)-MOD-DIOP (1 or 2) showed very high enantio-selectivity in the catalytic asymmetric hydrogenation of α-arylidenesuccinic acid half-esters (3). The optically active α-aryl-methylsuccinic acid half-esters (4) obtained are useful inter-madiates for the synthesis of optically active lignans. Total syntheses of (+)-collinusin (7), (-)-deoxypodophyllotoxin (9), and (+)-neoisostegane (14) were achieved using asymmetric hydrogenation catalyzed by the rhodium(I) complex with (S,S)-MOD-DIOP (2) as a key reaction. Thus, the absolute configurations of natural (+)-collinusin (7) and (+)-neoisostegane (14) were determined to be (R) and (M,6R,7R), respectively. The present asymmetric hydrogenation can provide a practical method for the synthesis of various optically active lignans.

著者

飯田 彰 松本 洋亘 富岡 清 和田 俊一

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 44 (ISSN:24331856)

巻号頁・発行日

pp.617-622, 2002-09-01 (Released:2017-08-18)

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DNA topoisomerases are nuclear enzymes responsible for biological processes of DNA metabolism such as replication, transcription, recombination and chromosome segregation at mitosis. Therefore, compounds that inhibit these enzymes as the primary cellular target are of special interest since those are promising candidates for anticancer drugs. Our previous studies demonstrated that the ortho-quinone or catechol moiety in aza-deoxypodophyllotoxin analogues plays a critical role in showing topoisomerase II (topo II) enzyme inhibition, in which proton transport during cutting and resealing of DNA is presumed to be blocked by a small structural unit like ortho-quinone. We report herein the synthesis and biological evaluation of nucleoside analogues as novel topo II inhibitors that are hybrids with aza-podophyllotoxin analogues. Our synthesis contains a Michael addition reaction of 1,3-dithianes to chiral butenolide 2, an equivalent to the deoxyribose moiety of a nucleoside, and a Silyl-Hilbert-Johnson reaction as key reactions. As predicted, ortho-quinone 1 and catechol 6 showed topo II inhibition, while dimethoxy derivative 7 was inactive. Unexpectedly, intermediates 6 and 8 were shown to be potent inhibitors. In addition to the active nucleosides, it was found that several lactone derivatives lacking a thymine base also inhibited topo II, indicating that a thymine base is not requisite to topo II inhibition. Structure-activity relationship of these lactone derivatives showed that the presence of the TBS group or dithiane moiety in the molecule is essential for topo II inhibition in the case of non-nucleoside derivatives. Further study is now in progress to examine their possible mechanism of action as topo II inhibitors.

著者

亀谷 哲治 津吹 政可 日暮 勝之 加藤 正 本多 利雄

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 27 (ISSN:24331856)

巻号頁・発行日

pp.176-183, 1985-09-07 (Released:2017-08-18)

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The stereocontrolled synthesis of steroid side chain has been developed. The major interest has been forcused on the synthesis of the side chain of ecdysone as well as crustecdysone from 20-oxosteroid via furan derivatives. Reduction of the olefin (21) over palladium-carbon afforded the (20S)-20-furylsteroid (22), stereoselectively, whose hydrogenation over rhodium-alumina, followed by ruthenium tetroxide oxidation and treatment with methylmagnesium bromide, gave the triols (28) and (29) having an ecdysone-type side chain, respectively. The stereoselective reduction of the lactone (33) as a key reaction to give the δ-lactone (35) and the γ-lactone (36), under various conditions has also been investigated. Grignard reaction of both lactones with methylmagnesium bromide led to the synthesis of the tetraol (37) possessing a crustecdysone side chain. The total synthesis of 2-deoxycrustecdysone (3) has also been achieved by application of the above method.

著者

南 篤志 劉 成偉 田上 紘一 松本 知之 Jens Christian Frisvad 鈴木 秀幸 石川 淳 五味 勝也 及川 英秋

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 57 (ISSN:24331856)

巻号頁・発行日

pp.Oral34, 2015 (Released:2018-10-01)

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ペニトレムA(1)は、Penicillium crustosumなどの糸状菌から単離されたインドールジテルペンである(図1)1。同菌は、酸化度や修飾様式が異なる構造類縁体{ペニトレムB-F(2-6)}に加えてパスパリン(7)2、PC-M5(8)、PC-M4(9)なども生産する3, 4。1は、パキシリン(10)やアフラトレム、ロリトレムなどの多くのインドールジテルペンと同様に7をコア骨格とする一方、インドール環上にある4-6縮環骨格や8員環エーテルなど他のインドールジテルペンではみられない特徴的な構造を有する(図1)。その特異な化学構造は有機合成化学者からも注目され、4については全合成も達成されている5。一方、その生合成については、標識化合物の投与実験などから1-6が生合成後期における酸化的修飾によって構築されると推定されていたものの6、骨格構築機構については不明であった。最近我々は、麹菌異種発現系を用いることで17種の遺伝子が関与するペニトレム生合成マシナリーの解明に成功し、特徴的な骨格構築機構を含む生合成経路の解明に成功した7。本討論会ではその詳細を報告するとともに、我々が改良してきた麹菌異種発現の有用性についても議論したい。ペニトレム生合成遺伝子クラスターの同定 ペニトレム生合成マシナリーの解明へ向け、生合成遺伝子の探索を試みた。予想生合成中間体である7の生合成に関与する遺伝子(paxGCMB)8を指標としてペニトレム生産菌(P. simplicissimum9)のドラフトゲノムデータを精査したところ、ptmGCMBを含む15個の読み枠から構成される生合成遺伝子クラスター(cluster 1:図2)を見いだした。しかしながら、酸化的な修飾反応を触媒する酵素遺伝子が明らかに不足していたため、遺伝子クラスターの分断が示唆された。分断した遺伝子クラスターを同定するためにRNA-Seqによる発現解析を生産/非生産条件で行ったところ、4種の酸化酵素遺伝子と1種のプレニル基転移酵素を含む遺伝子クラスター(cluster 2:図2)を新たに見いだした。1と同じ分散型生合成遺伝子クラスターはfusicoccin10、austinol11などで報告されているが、いずれも類縁化合物の相同遺伝子もしくは経路特異的な遺伝子を指標としてゲノムデータから探索されたものである。これに対して本結果は、植物由来の天然物と同様、発現解析が糸状菌天然物における分散型遺伝子クラスターの同定において有効であることを示す結果であると考えている。 麹菌異種発現系を利用したペニトレム生合成マシナリーの解明 最近我々は麹菌を宿主とした異種発現システムに着目し、代表的な糸状菌由来二次代謝産物であるインドールジテルペン7,8,12、テルペン13、ポリケタイド14の生合成マシナリーの再構築と物質生産を行ってきた。本手法の特徴は、①導入した遺伝子の確かな機能発現、②生合成経路の同定と物(View PDFfor the rest of the abstract.)

著者

鈴木 智大 小川 哲弘 阿部 暢男 赤地 拓澄 増田 貴久子 小山 智之 矢澤 一良 河岸 洋和

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.49, pp.383-388, 2007

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Osteoporosis is caused by an imbalance between bone resorption and bone formation, which results in bone loss and fractures after mineral flux. Osteoclast-like multinucleated cells can be differentiated in vitro from co-cultures of mouse bone marrow cells and osteoblastic cells by treatment with osteotropic factors, 1α,25-dihydroxyvitamin D3 (1α,25(OH)_2D_3) and prostaglandin E2 (PGE2). During screening for osteoclast-formation suppressing effects of the extracts of various mushrooms by using the assay, we found very strong activity in the extract of the mushroom Agrocybe chaxingu. Therefore, an attempt was made to isolate the active principles from mushroom and to determine their structures. Powder of the dried fruiting bodies of Agrocybe chaxingu was extracted with CH_2Cl_2, EtOAc and then EtOH. The CH_2Cl_2-soluble fraction only showed the suppressing activity. After repeated chromatography of the fraction, compounds 1 and 2 were purified as the active principles. Osteoclast differentiation was estimated by TRAP-(+) multinucleated cell formation. The addition of compound 1and 2 (3.1μg/ml, 6.8mM) reduced the number of TRAP-(+) multinucleated cells to 66% and 0%, respectively.

著者

井原 正隆 川口 明洋 加藤木 守 千尋 正利 福本 圭一郎 亀谷 哲治

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 28 (ISSN:24331856)

巻号頁・発行日

pp.339-346, 1986-09-09 (Released:2017-08-18)

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Synthesis of angularly tricyclopentanoid sesquiterpenes, was investigated via tricyclo[7.3.0.0^<1,5>]dodecane derivatives using intramolecular Diels-Alder reaction or intramolecular double Michael reaction as a key step. (1) Highly Stereoselective Total Synthesis of (±)-3-Oxosilphinene via Intramolecular Diels-Alder Reaction-(E,E)-3-(8-Phenylthio-octa-5,7-dien-2-yl)-2-methyl-2-cyclopenten-1-one (19) was prepared from the bromocyclopentenone (16) in three steps. Cycloaddition of 19 gave only one stereoisomer of the tricyclo[7.3.0.0^<1,5>]dodecene (20) having all correct four contiguous asymmetric centers. The cyclo-adduct (20) was converted into the tricyclo[6.3.0.0^<4,8>]undecane (25) via Wolff rearrangement. According to usual procedures, the ester (25) was then transformed into (±)-3-oxosilphinene (1). (2) Synthetic Study of Pentalenene and Pentalenic Acid via Intramolecular Double Michael Reaction-Barbier reaction of 4,4-dimethyl-2-cyclopenten-1-one (34) followed by oxidation with pyridinium chlorochromate gave the enone (36), which was converted into the bis-enone (33) in four steps. Intramolecular double Michael reaction of 33, carried out by heating with trimethylsilyl chloride, triethylamine, and zinc chloride, gave tricyclo[7.3.0.0^<1,5>]dodecanediones (40), which were subjected to Wolff rearrangement to afford the tricyclo[6.3.0.0^<4,8>]undecanes (41) possessing all carbon skeleton of natural products (4 and 5).

著者

廣瀬 紗弓 戸松 薫 柳瀬 笑子

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 55 (ISSN:24331856)

巻号頁・発行日

pp.PosterP-19, 2013 (Released:2018-03-09)

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1.序論茶(Camellia sinensis)は全世界で愛飲されている飲み物であり、近年の健康志向の高まりとともにその生理的機能が注目されている。カテキン類は茶葉に多く含まれるポリフェノール化合物であり、抗酸化作用、抗がん作用などの様々な生理的機能が見出されている。茶葉中のカテキン類は、紅茶やウーロン茶の製造過程の発酵により酸化、重合し、特徴的なtheaflavinやtheasinensin、oolongtheaninとなることが知られている(Fig.1)。これらにもカテキン類と同等、もしくはそれ以上の生理的機能が期待されているが、含量は非常に少なく分離精製も困難であるが故にその詳細な研究は難しく、また高収率な有機化学的合成法も確立されていない。そこで本研究では、カテキン類の酸化縮合反応の解明を目的として、反応部であるカテキンB環部のモデル化合物を用い、酸化反応について検討した。また、galloyloolongtheanin (1)の合成を目的とし、(-)-EGCg (2)の酸化反応についても検討した。Fig.1 カテキン二量体2.カテキンB環部のモデル化合物を用いた酸化反応 酸化剤としてフェチゾン試薬(炭酸銀-セライト)を用い、5位置換ピロガロール (3)と4位置換カテコール (4)を酸化しtheaflavin類のモデルであるベンゾトロポロン類縁体 (5)を合成した。様々な置換基を持つB環部モデル化合物で反応を行ったところ、5の収率は置換基の種類によって著しく変化した。その原因として、置換基の立体障害や電子供与性が影響している可能性が示唆された。そこで、さらに様々な置換基をもつ3と4を用いて合成を検討したところ、置換基の立体障害による反応性の低下が原因であることが分かった。さらに、5の収率が低い場合において副生成物が確認された。各種機器分析及び誘導化反応の結果、2分子の3が酸化的に縮合した化合物6が生成していることが判明し、6はさらに水と反応してより安定な化合物7となることが分かった。これらの結果から、5の収率低下の原因は、置換基の立体障害による3、4間の反応性の低下による副生成物の生成であることが示唆された(Fig.2)。カテキン類の酸化剤としてはPd/C 1)やK3[Fe(CN)6]2,3)等が知られており、theasinensin A (8)は2をCuCl2で酸化し、アスコルビン酸で還元することで得られることが報告されている4)。そこで、3を同条件で反応させたが、8を部分構造にもつ化合物は得ることができず、6が高収率で得られた。他の酸化剤としてK3[Fe(CN)6]やNaIO3を用いた場合でも同様であり、このことから、3の酸化では実際のカテキン類とは異なる位置選択性を示すことが明らかとなった。Fig.2 カテキンB環部モデル化合物の酸化反応3.(-)-EGCgの酸化反応 1の生成機構を解明するために、2の酸化反応の検討を行った。酸化剤としてPd/CやK3[Fe(CN)6]を用いた場合、8及び9が得られた。CuCl2を用いた場合では、9は得られず、アスコルビン酸で還元することで8が得られた。8が1の生成中間体であると推定しさ(View PDFfor the rest of the abstract.)

著者

泰地 美沙子 山崎 俊正 河原 一樹 元岡 大祐 中村 昇太 豊島 正 大久保 忠恭 小林 祐次 西内 祐二

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.53, pp.199-204, 2011

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Marinostatin (MST) isolated from a marine organism is a serine protease inhibitor consisting of 12 amino acids with two internal ester linkages formed between the β-hydroxyl and (β-carboxyl groups, Thr^3-Asp^9 and Ser^8-Asp^<11>. MST was synthesized by regioselective intramolecular esterification employing two sets of orthogonally removable side chain protecting groups for Ser/Thr and Asp. SAR study revealed that the ester linkage with Thr^3-Asp^9, the cis-conformation at Pro^7 and the N-terminal Phe^1-Ala^2 are the structural requirements for expression of the inhibitory activity. These findings were also supported by analyzing the solution and enzyme-bound structures of MST. Of particular note is that cis-Pro^7 may promote the internal hydrogen bond between the NH proton of Are and the carbonyl oxygen atom of the ester linkage with Thr^3-Asp^9 to protect its scissile bond of Met^4-Arg^5. This could be responsible for enhancing the potency. To elucidate the importance of backbone conformation at position 7, 16 and cis/trans-olefin analogs 17/18, in which cis/trans-olefins are substituted for the amide bond of Tyr^6-Ala^7, were synthesized. Although Ala^7 in 16 takes a trans-conformation in the solution structure, it takes a cis-conformation in the enzyme-bound structure. This implies that Ala^7 would isomerize from a trans to cis conformation when it binds to an enzyme, resulting in a certain inhibitory potency. However, the trans-olefin analog 18 lost the potency while the cis-olefin analog 17 displayed almost the same potency as that of MST. These results clearly indicated that the cis-conformation at position 7 is indispensable for binding to an enzyme in a canonical manner. By applying the structural motif of MST, we were able to rationally design protease inhibitory specificities that differed from those of the natural product.

著者

早川 謙二 麻生 和義 大薄 悟 兼松 顕

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.30, pp.387-394, 1988

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Intramolecular cycloadditions of Allenes constitute the versatile methods for the stereocontrolled synthesis of variously functionalized polycyclic compounds. Especially, intramoleclar Diels-Alder reactions using allenic dienophiles can full enjoy the merits of the unique structure of allens and proceed with extraordinary ease. On the basis of this strategy, several new synthtic methodologies were developed; (1) the intramolecular Diels-Alder reaction of allenyl ethers followed by hydration andoxidation provided a new polycyclic lactone synthesis (Scheme 1). This method was successfully applied to the total synthesis of platyphyllide 30(Scheme 5). (2) The allenyl ether bearing a substituent at C-2 position (ex.,1c,1d) underwent the tandem [2+2] cycloaddition and [3,3] sigmatropic rearrangement to produce the novel product having an bicyclo [n.3.11 carbon ring system (ex., 5c, 5d) (Scheme 2).

著者

内田 有紀 杉村 秀幸

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.46, pp.425-429, 2004

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Arohynapenes are new anticoccidial agents, isolated from the fermentation broth of Penicillium sp. FO-2295 strain and their structures have been proposed as shown in Fig. 1. Although the absolute stereochemistry of arohynapenes are unclear, in comparison with the spectral data of an analogous natural product, tanzawaic acid A, the relative stereochemistry of arohynapene B is deduced to be cis. In this study, we planed the total synthesis of racemic arohynapene B starting from cis-3,5-dimethylcyclohexanone in order to confirm its relative stereochemistry. Treatment of cis-3,5-dimethylcyclohexanone (2), prepared from 3,5-dimethyl-2-cyclohexen-1-one (1) via stereoselective hydrogenation (H_2, Pd/C), with ethynylmagnesium bromide, followed by acetylation gave propargyl acetate derivative 3. Acetate 3 rearranges in benzene containing a catalytic amount of silver trifluoroacetate under reflux to afford 1,3-dienyl acetate 4, which underwent Diels-Alder reaction with dimethyl acetylenedicarboxylate. After heating in toluene under reflux for four days, the reaction mixture was treated with DBN to provide tetrahydronaphtalene-dicarboxylate derivative 5. With the tetrahydronaphthalene skeleton in hands, we next focused the elongation of the dienylcarboxylic acid side chain. After reduction of diester 5 with LAH, selective protection of the 2-hydroxymethyl group in diol 6 was investigated. Moderate selectivity was observed when TBSCl-imidazole/DMF was used for the protection condition. Oxidation of the remaining hydroxy group to aldehyde, followed by Horner-Wadsworth-Emmons reaction gave unsaturated ester 9, which was subjected to reduction, oxidation and HWE reaction afforded protected arohynapene B. Finally, hydrolysis of the ester moiety, followed by cleavage of the silyl ether under mild acidic condition furnished (±)-arohynapene B.

著者

安藤 邦雄 佐々木 弘 細川 知良 縄田 喜治

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 18 (ISSN:24331856)

巻号頁・発行日

pp.317-323, 1974-10-01 (Released:2017-08-18)

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Molecular structure and absolute configuration of 4-o-ethyl ascofuranone (C_<23>H_<28>O_5Cl・C_2H_5) were determined by X-ray crystal structure analysis. Crystal structure was solved by the multisolution method. Dihydro-2,2-dimethyl-furan-3-one ring in the molecule adopts an envelope conformation, and the spatial configuration around the asymmetric carbon on the ring is Sinister according to the notation by Cahn, Ingold and Prelog. ORD and CD spectra were consistent with the ketone octant rule which predicted negative Cotton effect for the carbonyl n-π transition. Proton NMR spectra indicated that the ring was rigid, and its conformation in the solution was approximately identical to that in the crystal. All these results are the first stereochemical data on dihydro-2,2-dimethyl-furan-3-one ring in natural product.

著者

山本 恵子 山田 幸子 大田 雅照

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 36 (ISSN:24331856)

巻号頁・発行日

pp.290-297, 1994-09-20 (Released:2017-08-18)

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Hydroxyl groups play a major role in binding to a receptor protein. To clarify the side chain conformation of 1,25(OH)_2D_3 (1) to bind to VDR, we analyzed the mobility of the side chain of 1 and its 20-epimer (2) in terms of the spatial region accessible by the 25-hydroxyl group and the results were displayed as a dot map. The dot map indicates that each vitamin D has two major densely populated regions: A and G for 1 and EA and EG for 2. We designed six 22-substituted analogs of active vitamin D, 3-8, whose side chain hydroxyl is restricted to occupy one of the four spatial regions defined above and the analogs were classified into group A, G, EA, and EG accordingly. Syntheses of analogs, 3-8, were performed via diastereoselective conjugate addition of alkyl cuprate to steroidal (E)-and (Z)-22-en-24-ones (12 and 13) and -22-en-24-oates (16, 17, 20 and 21) as the key step. The activity of the analogs, 3-8, to bind to VDR was examined in compared with 1. It is apparent that the members of A ( 4 and 6) and EG (7) group analogs show much higher activity than the others, G(3, 5) and EA (8). The contrasting activities of the two 22-methyl analogs (3 and 4) are especially outstanding: VDR binding (3:4:1=1/50:1/3:1); differentiation of HL-60 cells (3:4:1=1/70:1:1). The results suggest that the conformation of 1,25(OH)_2D_3 (1) involved in binding to VDR and responsible for activity is the C(17,20,22,23)-anti form and the region where the 25-hydroxyl group occupies is the A.

著者

杉山 重夫 本田 昌徳 古森 徹哉

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.31, pp.22-29, 1989

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In our study on the isolation and structure elucidation of biologically active compounds from marine invertebrates, we synthesized the four diastereomers of C_<16>-phytosphingosine (10, 12, 25, and 26), acanthacerebroside A (1), and D-galactosylceramide (3b) as described below. (2S, 3S)-Allylic alcohol, which was prepared from the L-serine derivative and the (E)-vinylalane compound, was converted into (2S, 3S, 4R)- and (2S, 3S, 4S)-phytosphingosines by epoxidation, DIBAH reduction, and debenzylation. The same treatment of (2S, 3R)-allylic alcohol gave (2S, 3R, 4R)- and (2S, 3R, 4S)-phytosphingosines. (2R)-Acetoxytetracosanoic acid was prepared and coupled to (2S, 3S, 4R)-phytosphingosine to give the ceramide (34). Glycosylation of 34 gave the desired monoglycoside (36) and the bisglycoside (37). 36 was converted into 1 by deacetylation. New D-galactosylceramides were isolated from Chondropsis sp., but the absolute stereochemistry has not been determined. Therefore, (2S, 3S, 4R, 6E)- and (2R, 3R, 4R, 6E)-phytosphingosines were prepared via asymmetric epoxidation. The former was transformed to (2S, 3S, 4R, 6E, 2'R)-D-galactosylceramide and its heptaacetate. The spectral data of them were in excellent agreement with those of the natural specimens.

著者

酒井 浄 石黒 靖尚 舟越 和久 上野 貢嗣 末宗 洋

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 26 (ISSN:24331856)

巻号頁・発行日

pp.299-306, 1983-09-15 (Released:2017-08-18)

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Variously functionalized cyclopentanones are important as starting materials for the synthesis of natural products. We have succeeded in a simple, highly stereospecific synthesis of five membered ring ketone using Wilkinson complex. Thus, the precursors, 1-al-4-enes(4a-e,11,13) prepared in optically active form from D-limonene, (+)-limonen-10-ol and 1-carvone in three steps were submitted for RhCl(PPh_3)_3-catalyzed cyclization in CH_2Cl_2 to afford the cis-3,4-disubstituted cyclopentanones(14-22) in good yield (Table 2). The following results were obtained in this cyclization. 1) In all cases, the cis-3,4-disubstituted cyclopentanones were stereospecifically obtained as the sole products. 2) The cyclization reaction of the six membered lactols(12,13) was found to proceed very slowly even if at high temperature. 3) The cis-3,4-disubstituted cyclopentanones obtained in this method were also found to be applicable for the synthesis of bicyclic ketone(23). 4) The configurations of 3,4-disubstituents in each compounds were clarified by the way of chemical correlation and spectral analyses. Further application for the synthesis of ent-cis,cis-dihydro-nepetalactone(39) will be discussed.

著者

末宗 洋 上野 貢嗣 川原 哲也 小田 晃造 舟越 和久 酒井 浄

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 27 (ISSN:24331856)

巻号頁・発行日

pp.108-114, 1985-09-07 (Released:2017-08-18)

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In the synthesis of natural products consisting of the basic structure of cyclopentane ring, variously functionalized cyclopentanones are required as starting materials. Previously, we succeeded in a simple, highly stereospecific synthesis of the cis-3,4-disubstituted cyclopentanones by the mild reaction with RhCl(PPh_3)_3. By the application of this newer cyclization reaction, we have succeeded in the synthesis of cis,cis-dihydronepetalactone, prostanoic acid, 8-isoprostanoic acid, (+)-brefeldin A and carbacyclin in the optically active form from limonene or Corey lactone. These compounds were synthesized via the following key steps. 1) 3-(3-Oxobutyl)cyclopentanone was easily converted to the deconjugated bicyclic enone (3→4). 2) The regioselective alkylation of limonene was performed by using s-BuLi-TMEDA (1→8). 3) The cis-3,4-disubstituted cyclopentanone from limonen-10-ol could be converted to the trans-3,4-disubstituted cyclo-pentanone by the epimerization (15→16, 22→23).

著者

浜道 則光 藤多 哲朗 松崎 徹 北尾 有紀 城内 正寿 広瀬 良治

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 37 (ISSN:24331856)

巻号頁・発行日

pp.79-84, 1995-09-01 (Released:2017-08-18)

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Mycestericins D (1), E (3), F (2) and G (4), new immunosuppressants, were isolated from the culture broth of Mycelia sterilia ATCC 20349. The immunosuppressive activities of 1 and 2 exhibited an IC_<50> of 16nM and 120nM against mouse allogeneic mixed lymphocyte reaction (MLR), respectively, while 3 and 4 exhibited an IC_<50> of 13nM and 370nM, respectively. The proposed structures were unambiguously confirmed by spectroscopy, chemical evidence and total synthesis. Their absolute configurations have been determined by comparison of their CD spectra with those of synthetic compounds (R and S)-9 prepared from methyl (2S, 4R)-2-tert-butyl-3-formyl-oxazolidine-4-carboxylate (5) and stearoyl chloride. Thus, mycestericins D (1) and F (2) were assigned to be 2 (S), 3 (S) configurations, while mycestericins E (3) and G (4) were 2 (S), 3 (R) configurations. The first total synthesis of mycestericins have been achieved from 5 and 1,8-octanediole (10). The alkyl chain moiety 21 was prepared in 12 steps from 10 by straightforward reactioin. The key intermediate 22 obtained from 5 and 21 could be converted to the desired final compounds. Stereoselective reduction of the ketone 22 with Zn(BH_4)_2 or NaBH_4 provided the (R)-hydroxy 23, the protecting groups of which were removed with 10% MeOH in CF_3COOH, followed by hydrolysis of 24 to give mycestericin E (3). On the other hand, mycestericin D (1) was synthesized from 22 by deprotection, followed by reduction of 25 with Me_4NBH(OAc)_3 and then hydrolysis of 26. Hydrogenation of mycestericin D (1) and E (3) provided the corresponding F (2) and G (4).

著者

藤多 哲朗 浜道 則光 内田 秀治 加治 隆史 松本 範正 広瀬 良治 北尾 郁紀 松崎 徹 千葉 健治

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 38 (ISSN:24331856)

巻号頁・発行日

pp.727-732, 1996-09-02 (Released:2017-08-18)

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2-Aminoalcohol was shown to be the minimum essential structure for the immunosuppressive activity of 2-alkyl-2-aminopropane-1,3-diol, which was generated by modification of ISP-I (1: myriocin, thermozymocidin). 2-Aminoalcohols 4a-h were examined for immunosuppressive activity on mouse allogeneic mixed lymphocyte reaction (MLR) in vitro. The series showed a bell-shaped relationship between the activity and the carbon numbers. Among them, 2-aminohexadecanol (4c) was the most potent. In order to investigate relationship between the activity and the configuration at C-2 in 2-aminoalcohol, (R)- and (S)-isomers of 4c, 2-aminoeicosanol (4h) and 2-amino-4-(4-octylphenyl)butanol (5) were prepared and examined for the activity on mouse allogeneic MLR. As a results, the (R)-isomers were more potent the (S)-isomers, and (R)-4c displayed comparably activity to FTY720 (3), which is expected as a powerful candidate for safer immunosuppressant for organ transplantations and for the treatment of autoimmune diseases.

著者

亀谷 哲治 鈴木 幸夫 伴 千恵子 三沢 薫 高田 信子 叶田 清 本多 利雄

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 29 (ISSN:24331856)

巻号頁・発行日

pp.63-70, 1987-07-25 (Released:2017-08-18)

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Chiral cyclopentane derivatives have widely been employed as important starting materials in the syntheses of naturally occurring compounds. Development of an efficient preparation of a chiral cyclopentane derivative from readly available substances with both (+)- and (-)-forms is therefore desirable. We have established an efficient procedure for the preparation of chiral 2-isopropeny1-5-methyl-4-oxocyclo-pentane-1-carboxylate(1) and (2), whose substituents would be transformed into variety of functional groups, from readily avairable (-)- and (+)-carvone. First, the (-)-isomer(1) was employed in the synthesis of (+)-tecomanine (7), an antipodal form of hypoglycemic monoterpene alkaloid, where the aminylium ion-induced cyclization played an important role. Whereas, N-acetyl-L-acosamine (32), found as a structural component of glycosidic antibiotic, was also derived from the (+)-isomer (2) by utilizing the Beckmann rearrangement and Baeyer-Villiger oxidation as key reactions. Finally, Melillo's lactone(34), a key intermediate for the synthesis of carbapenem antibiotic (+)-thienamycin, was prepared from (-)-isomer(1) by manipulation of its substituents in reasonably high-yield.

著者

チャンサカオ スニー 石川 勉 関 宏子 関根 啓子 岡田 峯明 樋口 義洋 チャイチャンティピュース チャイヨー

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 42 (ISSN:24331856)

巻号頁・発行日

pp.49-54, 2000-10-01 (Released:2017-08-18)

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"Kwao Keur." which had been identified as Puraria mirifica (Leguminosae), has long been used in Thailand and Burma as a rejuvenating folk medicine and has a fascinating history. A potent estrogenic principle has been known to be an unusual phenol miroestrol (1). Although the possible presence of an alternative active component was suggested, there has been no isolation of any other powerful phytoestrogens. with further studies leading instead to the isolation of isoflavonoids. These situation made us re-investigate the estrogenic principles of P. mirifica. The bioassay-guided separation of the ethyl acetate extract of the tuberous roots of P. mirifica by chromatographic techniques resulted in the successful isolation of a new phytoestrogen. (+)-deoxymiroestrol (4). together with (+)-1 and (+)-isomiroestrol (7). The structure of (+)-1 had been determined by X-ray crystallographic analysis and its enantioselective total synthesis was recently reported. Thus. the structure of (+)-deoxymiroestrol (4) was established by comparison of its NMR data with those of (+)-1. The growth-promoting effect of them on MCF-7 human breast cancer cells showed the strongest activity with 4. Interestingly. 4 was easily converted into 1 and 7 by aerial oxidation. suggesting that 4 may be the actual phytoestrogen of P. mirifica. On the other hand daidzein (2), genistein (3), and coumestrol (6) belong to isoflavonoids were isolated as phytoestrogens with lower activity. In addition, it was found that kwakhurin (5). a characteristic isoflavonoid in this plant. also showed the same activity as 2.

著者

吉村 誠司 善光 龍哉 大津 嘉弘 金崎 竜一 重松 伸治 高瀬 茂弘 閨 正博

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 45 (ISSN:24331856)

巻号頁・発行日

pp.281-286, 2003-09-01 (Released:2017-08-18)

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During the course of seeking for novel gluconeogenesis inhibitors, FR225659 and its four congeners were isolated from the fermentation broth of Helicomyces sp. No.19353. Series of NMR analysis allowed elucidation of their planar structures. The planar structure of FR225659 includes a novel acyl moiety, an unprecedented amino acid residue, 3-chloro-4-hydroxyarginine, and two unique amino acid residues, a 3-hydroxy-3-methylproline and a dehydrovaline. As all efforts to obtain crystals of 1 suitable for X-ray crystallography turned out to be in vain, a combination of chemical modification and spectroscopic methods was applied to elucidate the stereochemistry of 1. Acid hydrolysis followed by derivatization with chiral phthalic acid allowed X-ray crystallographic analysis of the proline analogue, which determined its stereochemistry to be (2S, 3R). Conformational analysis of 9 using ^<2,3>J_<CH> developed by Murata et. al. allowed assignment of the relative stereochemistry of the arginine analogue to be 2,3-erythro-3,4-threo. Then, the modified Mosher's method suggested that the absolute configuration of 4'-C is R, which was supported by NOE analysis of 1. The CD spectrum of 1 showed positive Cotton effect at 236nm, indicating an optical activity around the biphenyl axis between the quinoline and the phenol of 1. As the CD spectrum lacking clear Davydov split does not appear to be easy to translate, further elucidation of the axial chirality is now in progress. FR225659 family exerted potent inhibitory activities against glucagon-induced gluconeogenesis of rat primary liver cells, while they showed ten or more times less potent cytotoxicities against EL-4 cell line. As they do not suppress gluconeogenesis independent of glucagon, they should stop a signal pathway from glucagon. Diabetes patients are reported to produce more hepatic glucose than normal, and this leads to complications unless properly treated. Thus, FR225659 family can be drug candidates for diabetes to down-regulate the high blood glucose level of those patients. It is noteworthy that the hydroxyl group at position 3" plays important roles in both biological activities and solubility in various solvents.