JP2014172821A - Optically active thiochroman derivative and method for producing the same - Google Patents

Optically active thiochroman derivative and method for producing the same Download PDF

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JP2014172821A
JP2014172821A JP2013044110A JP2013044110A JP2014172821A JP 2014172821 A JP2014172821 A JP 2014172821A JP 2013044110 A JP2013044110 A JP 2013044110A JP 2013044110 A JP2013044110 A JP 2013044110A JP 2014172821 A JP2014172821 A JP 2014172821A
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thiochroman
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thiochroman derivative
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JP6061223B2 (en
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Takayoshi Arai
孝義 荒井
Yuji Yamamoto
悠史 山本
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Chiba University NUC
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Abstract

PROBLEM TO BE SOLVED: To establish a means of synthesizing a thiochroman derivative.SOLUTION: Provided is a thiochroman derivative represented by formula (2) (where, Rand Rmay respectively independently use H, Me, Et, tBu, halogen, alkoxy and a nitro group; and Rand Rmay be plurally coupled at any position).

Description

本発明は、光学活性チオクロマン誘導体及びその製造方法に関する。   The present invention relates to an optically active thiochroman derivative and a method for producing the same.

光学活性なアミノ酸や糖を基本構成単位とする生体高分子は、高度な不斉空間を構築しており、この生体高分子を受容体とする医薬品も光学活性を有している必要がある。このような光学活性な物質を合成する方法は不斉合成法と呼ばれており、不斉合成法の中でも少量の不斉源から理論上無限の光学活性体を合成することが可能な触媒的不斉合成法は極めて有用、重要なものとなっている。   A biopolymer having an optically active amino acid or sugar as a basic structural unit constructs a highly asymmetric space, and a drug using the biopolymer as a receptor needs to have optical activity. Such a method for synthesizing an optically active substance is called an asymmetric synthesis method. Among the asymmetric synthesis methods, a catalytically capable of synthesizing a theoretically infinite optically active substance from a small amount of an asymmetric source. Asymmetric synthesis methods are extremely useful and important.

現在、光学活性チオクロマン誘導体は有機触媒を用いることにより触媒的不斉合成が達成されており、例えば、従来の技術として、有機触媒を用いたチオサリチルアルデヒドの反応において、α,β−不飽和オキサゾリジノンを用いる例が下記文献1に、ベンジリデンマロネートを用いる例が下記文献2に、ニトロアルケンを用いる例が下記文献3に記載されている。   At present, optically active thiochroman derivatives have been achieved by catalytic asymmetric synthesis using an organic catalyst. For example, as a conventional technique, in the reaction of thiosalicylaldehyde using an organic catalyst, α, β-unsaturated oxazolidinone is used. The following document 1 describes an example using benzylidene, an example using benzylidene malonate in the following document 2, and an example using nitroalkene in the following document 3.

Zu,L.S.;Wang,J.;Li,H.;Xie,H.X.;Jiang,W.;Wang,W.J.Am.Chem.Soc.2007,129,1036.Zu, L .; S. Wang, J .; Li, H .; Xie, H .; X. Jiang, W .; Wang, W .; J. et al. Am. Chem. Soc. 2007, 129, 1036. Dodda,R.;Mandel,T.;Zhao,C.−G.Tetrahedron Lett.2008,49,1899.Dodda, R .; Mandel, T .; Zhao, C .; -G. Tetrahedron Lett. 2008, 49, 1899. Dodda,R.;Goldman,J.J.;Mandel,T.;Zhao,C.−G.;Broker,G.A.;Tiekink,E.R.T.Adv.Synth.Catal.2008,350,537.Dodda, R .; Goldman, J .; J. et al. Mandel, T .; Zhao, C .; -G. Broker, G .; A. Tiekink, E .; R. T. T. et al. Adv. Synth. Catal. 2008, 350, 537.

しかしながら、上記文献に記載のいずれにおいても、金属触媒を用いた例は無く、新規ジアステレオマーを合成する反応系の開発が望まれる。   However, in any of the documents described above, there is no example using a metal catalyst, and development of a reaction system for synthesizing a novel diastereomer is desired.

そこで、本発明は、上記課題を鑑み、下記式で示される反応のように、金属触媒による、チオサリチルアルデヒドとニトロアルケンのタンデムMichael/Henry反応により得られるチオクロマン誘導体合成を提供することを目的とする。
Therefore, in view of the above problems, the present invention aims to provide a thiochroman derivative synthesis obtained by tandem Michael / Henry reaction of thiosalicylaldehyde and nitroalkene with a metal catalyst, as in the reaction represented by the following formula. To do.

本発明者らは、上記課題について鋭意検討を行なっていたところ、下記式で示される反応のように、金属にイミダゾリン‐アミノフェノール配位子を配位させた触媒の存在下で、チオサリチルアルデヒドとニトロアルケンを反応させることで、Michael/Henry反応を行わせ、式(2)で示されるチオクロマン誘導体を得ることができる点を発見し、本発明を完成させるに至った。
The inventors of the present invention have been diligently studying the above problems, and as in the reaction represented by the following formula, in the presence of a catalyst in which an imidazoline-aminophenol ligand is coordinated to a metal, thiosalicylaldehyde It was discovered that a thiochroman derivative represented by the formula (2) can be obtained by reacting a nitroalkene with a nitroalkene, thereby completing the present invention.

即ち、本発明の一手段に係るチオクロマン誘導体を製造する方法は、下記式(1)で示される触媒の存在下で、チオサリチルアルデヒドとニトロアルケンを反応させることである。
That is, the method for producing a thiochroman derivative according to one means of the present invention is to react thiosalicylaldehyde and nitroalkene in the presence of a catalyst represented by the following formula (1).

なおこの結果、下記式(2)で示されるチオクロマン誘導体を得ることができる。
(ここでRおよびRは、おのおの独立して、H、Me、Et、tBu、ハロゲン、アルコキシ、又はニトロ基である。RおよびRは、いずれ位置に複数結合していてよい。)
As a result, a thiochroman derivative represented by the following formula (2) can be obtained.
(Here, R 1 and R 2 are each independently H, Me, Et, tBu, halogen, alkoxy, or nitro group. A plurality of R 1 and R 2 may be bonded at any position.) )

以上、本発明により、金属触媒による、チオサリチルアルデヒドとニトロアルケンのMichael/Henry反応およびそれにより得られるチオクロマン誘導体を提供することが可能となる。また、本発明によると下記式(2)で示されるチオクロマンを高化学収率、高ジアステレオ選択的、高エナンチオ選択的に得ることができる。
(ここでRおよびRは、おのおの独立して、H、Me、Et、tBu、ハロゲン、アルコキシ、又はニトロ基である。RおよびRは、いずれ位置に複数結合していてもよい。)
As described above, according to the present invention, it is possible to provide the Michael / Henry reaction of thiosalicylaldehyde and nitroalkene with a metal catalyst and the thiochroman derivative obtained thereby. Further, according to the present invention, a thiochroman represented by the following formula (2) can be obtained with high chemical yield, high diastereoselectivity, and high enantioselectivity.
(Wherein R 1 and R 2 are each independently H, Me, Et, tBu, halogen, alkoxy, or nitro group. R 1 and R 2 may be bonded in plural at any position. .)

以下、本発明の実施形態について図面を参照しつつ説明する。ただし、本発明は多くの異なる態様で実施することが可能であり、以下に示す実施形態に限定されるものではない。   Embodiments of the present invention will be described below with reference to the drawings. However, the present invention can be implemented in many different modes and is not limited to the embodiments shown below.

(実施形態1)
本実施形態に係るインドール誘導体の製造方法は、下記式(1)で示される触媒の存在下で、チオサリチルアルデヒドとニトロアルケンを反応させる。
(Embodiment 1)
In the method for producing an indole derivative according to this embodiment, thiosalicylaldehyde and nitroalkene are reacted in the presence of a catalyst represented by the following formula (1).

本実施形態において用いられる触媒における配位子は、その構成中に窒素で架橋されたイミダゾリン骨格とフェニル骨格とを有しているため、反応場が広い。またフェノール環にニトロ基を有するため活性が高い。   Since the ligand in the catalyst used in the present embodiment has an imidazoline skeleton and a phenyl skeleton bridged with nitrogen in its structure, the reaction field is wide. Moreover, since it has a nitro group in the phenol ring, its activity is high.

また、配位子を配位させる金属としては、配位させることができる限りにおいてこれに限定されるわけではないが、例えばニッケル、コバルト、または銅を例示することができる。また配位子を金属に配位させる方法としては、周知の方法を採用することができ、限定されるわけではないが、金属塩と配位子を混合することで配位させることができる。金属塩としては、限定されるわけではないが、金属がニッケルである場合、Ni(OAc)、Ni(acac)、Ni(OTf)等を用いることができる。 Moreover, as a metal which coordinates a ligand, as long as it can coordinate, it is not necessarily limited to this, For example, nickel, cobalt, or copper can be illustrated. Moreover, as a method of coordinating a ligand to a metal, a well-known method can be adopted, and although not limited, it can be coordinated by mixing a metal salt and a ligand. The metal salt is not limited, but when the metal is nickel, Ni (OAc) 2 , Ni (acac) 2 , Ni (OTf) 2 or the like can be used.

本実施形態に係る触媒は、チオサリチルアルデヒドとニトロアルケンを用いたMichael/Henry反応を行うために用いることができる。具体的には、本実施形態に係る触媒の存在下で、下記式で示される反応のように、チオサリチルアルデヒドとニトロアルケンを反応させてチオクロマン誘導体を合成することができる。
The catalyst according to this embodiment can be used to perform a Michael / Henry reaction using thiosalicylaldehyde and nitroalkene. Specifically, in the presence of the catalyst according to the present embodiment, a thiochroman derivative can be synthesized by reacting thiosalicylaldehyde and a nitroalkene as in the reaction represented by the following formula.

ここでRおよびRは、おのおの独立して、H、Me、Et、tBu、ハロゲン、アルコキシ、又はニトロ基である。RおよびRは、いずれ位置に複数結合していてもよい。 Here, R 1 and R 2 are each independently H, Me, Et, tBu, halogen, alkoxy, or nitro group. A plurality of R 1 and R 2 may be bonded at any position.

上記反応は、トルエン中において行なうことが好ましい。   The above reaction is preferably performed in toluene.

上記反応において、反応基質として用いられるチオサリチルアルデヒドは下記式(3)で示される。ここにおいてRは限定されるわけではないが、例えばH、Me、tBu、ハロゲン、アルコキシ基を用いることができる。なお、上記反応において、用いるチオサリチルアルデヒドの量は、ニトロアルケンを1モルとした場合、1モル以上2モル以下の範囲にあることが好ましく、より好ましくは1.2モル以上1.5モル以下の範囲内である。また、チオサリチルアルデヒドはスローアディションすることが望ましい。
In the above reaction, thiosalicylaldehyde used as a reaction substrate is represented by the following formula (3). Here, R 1 is not limited, but for example, H, Me, tBu, halogen, and alkoxy groups can be used. In the above reaction, the amount of thiosalicylaldehyde to be used is preferably in the range of 1 mol to 2 mol, more preferably 1.2 mol to 1.5 mol, with 1 mol of nitroalkene. Is within the range. Thiosalicylaldehyde is desirably slow-added.

上記反応において、反応基質として用いられるニトロアルケンは下記式(4)で示される。ここにおいてRは限定されるわけではないが、例えばH、Me、tBu、ハロゲン、アルコキシ、ニトロ基を用いることができる。
In the above reaction, a nitroalkene used as a reaction substrate is represented by the following formula (4). Here, R 2 is not limited, but for example, H, Me, tBu, halogen, alkoxy, nitro group can be used.

この結果、本実施形態に係る方法によると、下記式(2)で示すチオクロマン誘導体を得ることができる。
As a result, according to the method according to the present embodiment, a thiochroman derivative represented by the following formula (2) can be obtained.

ここでRおよびRは、おのおの独立して、H、Me、Et、tBu、ハロゲン、アルコキシ、又はニトロ基である。RおよびRは、いずれ位置に複数結合していてもよい。) Here, R 1 and R 2 are each independently H, Me, Et, tBu, halogen, alkoxy, or nitro group. A plurality of R 1 and R 2 may be bonded at any position. )

なおここで本実施形態に関わる触媒を用いた反応の機構について説明しておく。
イミダゾリン−アミノフェノール−ニッケル触媒の作用により、ニトロアルケンが活性化され、チオサリチルアルデヒドがMichael反応を起こす。この反応により生成したニッケルニトロナートがアルデヒドとHenry反応を起こし、生成物に至るとともに、触媒が再生する。
Here, the reaction mechanism using the catalyst according to the present embodiment will be described.
Under the action of an imidazoline-aminophenol-nickel catalyst, the nitroalkene is activated and the thiosalicylaldehyde undergoes a Michael reaction. Nickel nitronate produced by this reaction causes a Henry reaction with the aldehyde to reach the product, and the catalyst is regenerated.

(配位子の合成)
また本実施形態に係る配位子及び触媒は、合成できる限りにおいて限定されるわけではないが、例えば特開2011−6363号公報に記載の技術を用いて合成することができる。
(Synthesis of ligand)
In addition, the ligand and the catalyst according to this embodiment are not limited as long as they can be synthesized, but can be synthesized, for example, using the technique described in JP2011-6363A.

そしてこの配位子を12.8mg用い、これを酢酸ニッケル(II)に配位させることで触媒として不斉Michael/Henry反応を行なった。   Then, 12.8 mg of this ligand was used, and this was coordinated with nickel (II) acetate to carry out an asymmetric Michael / Henry reaction as a catalyst.

(実施例1)
本実施例は、上記触媒の存在下、無水トルエン1mLに溶解した(E)−(2−ニトロビニル)ベンゼン22.5mgを−40℃に保ち、2−メルカプトベンズアルデヒドのトルエン溶液(0.045M)5mL(1.5当量)を15時間かけてスローアディションすることで行った。この結果、下記に示す化合物(2−1)を47mg得ることができた。また、(2−1)の化学収率は>99%、ジアステレオ比は>99/1、エナンチオ過剰率は95%eeであった。
Example 1
In this example, 22.5 mg of (E)-(2-nitrovinyl) benzene dissolved in 1 mL of anhydrous toluene in the presence of the above catalyst was kept at −40 ° C., and toluene solution of 2-mercaptobenzaldehyde (0.045 M) 5 mL (1.5 equivalents) was slow-added over 15 hours. As a result, 47 mg of the compound (2-1) shown below was obtained. The chemical yield of (2-1) was> 99%, the diastereo ratio was> 99/1, and the enantiomeric excess was 95% ee.

H NMR (500MHz,Acetone−d)δ 7.59−7.61(m,2H),7.48−7.50(m,1H),7.39−7.42(m,2H),7.33−7.37(m,1H),7.30(dt,1H,J=7.8,1.5 Hz),7.20(dt,1H,J=7.5,1.2 Hz),7.15(dd,1H,J=8.1,0.9Hz),5.70(dd,1H,J=11.5,2.9Hz),5.40−5.46(m,2H),5.31(d,1H,J=11.8Hz);
13C NMR(100MHz,Acetone−d)δ 137.7,134.6,133.5,132.0,129.9,129.7,129.3,129.2,125.7,125.4,90.2,70.6,41.4;
Enantiomeric excess was determined by HPLC with a Chiralkap AD−H column (85:15 Hexane:2−Propanol,0.7mL/min,254nm); minor enantiomer t=14.6min, major enantiomer t=21.8min;95%ee
1 H NMR (500 MHz, Acetone-d 6 ) δ 7.59-7.61 (m, 2H), 7.48-7.50 (m, 1H), 7.39-7.42 (m, 2H) , 7.33-7.37 (m, 1H), 7.30 (dt, 1H, J = 7.8, 1.5 Hz), 7.20 (dt, 1H, J = 7.5, 1. 2 Hz), 7.15 (dd, 1H, J = 8.1, 0.9 Hz), 5.70 (dd, 1H, J = 11.5, 2.9 Hz), 5.40-5.46 ( m, 2H), 5.31 (d, 1H, J = 11.8 Hz);
13 C NMR (100 MHz, Acetone-d 6 ) δ 137.7, 134.6, 133.5, 132.0, 129.9, 129.7, 129.3, 129.2, 125.7, 125. 4,90.2,70.6,41.4;
Enantiomeric excess was determined by HPLC with a Chiralkap AD-H column (85:15 Hexane: 2-Propanol, 0.7mL / min, 254nm); minor enantiomer t r = 14.6min, major enantiomer t r = 21.8min; 95% ee

(実施例2)
本実施例は、上記触媒の存在下、無水トルエン1mLに溶解した(E)−1−メトキシ−4−(2-ニトロビニル)ベンゼン26.8mgを−40℃に保ち、2−メルカプトベンズアルデヒドのトルエン溶液(0.045M)5mL(1.5当量)を15時間かけてスローアディションすることで行った。この結果、下記に示す化合物(2−2)を48mg得ることができた。また、(2−2)の化学収率は>99%、ジアステレオ比は96/4、エナンチオ過剰率は84%eeであった。
(Example 2)
In this example, 26.8 mg of (E) -1-methoxy-4- (2-nitrovinyl) benzene dissolved in 1 mL of anhydrous toluene in the presence of the above catalyst was kept at −40 ° C., and a toluene solution of 2-mercaptobenzaldehyde was used. (0.045M) 5 mL (1.5 equivalents) was slow-added over 15 hours. As a result, 48 mg of the following compound (2-2) was obtained. Further, the chemical yield of (2-2) was> 99%, the diastereo ratio was 96/4, and the enantiomeric excess was 84% ee.

H NMR (Acetone−d,500MHz)δ 7.50−7.53(m,2H),7.47(dd,1H,J=7.8,1.5Hz),7.29(dt,1H,J=7.5,1.4 Hz),7.19(dt,1H,J=7.5,1.2 Hz),7.14 (dd,1H,J=8.0,1.2 Hz),6.93−6.96(m,2H),5.62(dd,1H,J=11.5,2.9 Hz),5.37−5.44(m,2H),5.25(d,1H,J=11.8Hz),3.79(s,3H);
13C NMR(Acetone−d,500MHz)δ 160.7,134.5,133.9,132.1,130.5,129.9,129.2,125.6,125.4,115.0,90.4,70.8,55.5,40.9;
Enantiomeric excess was determined by HPLC with a Chiralpak AD−H column (85:15 Hexane:2−Propanol,0.7 mL/min,254nm); minor enantiomer t=22.5min,major enantiomer t=35.4min;84% ee
1 H NMR (acetone-d 6 , 500 MHz) δ 7.50-7.53 (m, 2H), 7.47 (dd, 1H, J = 7.8, 1.5 Hz), 7.29 (dt, 1H, J = 7.5, 1.4 Hz), 7.19 (dt, 1H, J = 7.5, 1.2 Hz), 7.14 (dd, 1H, J = 8.0, 1. 2 Hz), 6.93-6.96 (m, 2H), 5.62 (dd, 1H, J = 11.5, 2.9 Hz), 5.37-5.44 (m, 2H), 5.25 (d, 1H, J = 11.8 Hz), 3.79 (s, 3H);
13 C NMR (Acetone-d 6 , 500 MHz) δ 160.7, 134.5, 133.9, 132.1, 130.5, 129.9, 129.2, 125.6, 125.4, 115. 0, 90.4, 70.8, 55.5, 40.9;
Enantiomeric excess was determined by HPLC with a Chiralpak AD-H column (85:15 Hexane: 2-Propanol, 0.7 mL / min, 254nm); minor enantiomer t r = 22.5min, major enantiomer t r = 35.4min 84% ee

(実施例3)
本実施例は、上記触媒の存在下、無水トルエン1mLに溶解した(E)−1−ニトロ−4−(2−ニトロビニル)ベンゼン29.1mgを−40℃に保ち、2−メルカプトベンズアルデヒドのトルエン溶液(0.045M)5mL(1.5当量)を15時間かけてスローアディションすることで行った。この結果、下記に示す化合物(2−3)を49mg得ることができた。また、(2−2)の化学収率は98%、ジアステレオ比は>99/1、エナンチオ過剰率は91%eeであった。
(Example 3)
In this example, 29.1 mg of (E) -1-nitro-4- (2-nitrovinyl) benzene dissolved in 1 mL of anhydrous toluene in the presence of the above catalyst was kept at −40 ° C., and a toluene solution of 2-mercaptobenzaldehyde was used. (0.045M) 5 mL (1.5 equivalents) was slow-added over 15 hours. As a result, 49 mg of the following compound (2-3) could be obtained. The chemical yield of (2-2) was 98%, the diastereo ratio was> 99/1, and the enantiomeric excess was 91% ee.

H NMR(Acetone−d,500 MHz)δ 8.27−8.30(m,2H),7.93−7.95(m,2H),7.50−7.52(m,1H),7.32(dt,1H,J=7.5,1.4Hz),7.23(dt,1H,J=7.5,1.2Hz),7.17−7.18(m,1H),5.80−5.83(m,1H),5.60(d,1H,J=5.2Hz),5.45−5.49(m,2H);
13C NMR(Acetone−d,125MHz)δ 148.8,145.5,134.4,132.7,132.3,130.7,130.2,126.0,125.3,124.8,89.5,70.6,40.6;
Enantiomeric excess was determined by HPLC with a Chiralcel OD−H column(80:20 Hexane:2−Propanol,0.7mL/min,254nm); major enantiomer t=37.3min,minor enantiomer t=49.3min;91%ee
1 H NMR (acetone-d 6 , 500 MHz) δ 8.27-8.30 (m, 2H), 7.93-7.95 (m, 2H), 7.50-7.52 (m, 1H ), 7.32 (dt, 1H, J = 7.5, 1.4 Hz), 7.23 (dt, 1H, J = 7.5, 1.2 Hz), 7.17-7.18 (m, 1H), 5.80-5.83 (m, 1H), 5.60 (d, 1H, J = 5.2 Hz), 5.45-5.49 (m, 2H);
13 C NMR (Acetone-d 6 , 125 MHz) δ 148.8, 145.5, 134.4, 132.7, 132.3, 130.7, 130.2, 126.0, 125.3, 124. 8, 89.5, 70.6, 40.6;
Enantiomeric excess was determined by HPLC with a Chiralcel OD-H column (80:20 Hexane: 2-Propanol, 0.7mL / min, 254nm); major enantiomer t r = 37.3min, minor enantiomer t r = 49.3min; 91% ee

以上の通り、本実施例によると、イミダゾリン−アミノフェノール−ニッケル触媒の存在下、チオサリチルアルデヒドとニトロアルケンを用いたジアステレオおよびエナンチオ選択的Michael/Henry反応を実現できた。   As described above, according to this example, diastereo- and enantioselective Michael / Henry reactions using thiosalicylaldehyde and nitroalkene could be realized in the presence of an imidazoline-aminophenol-nickel catalyst.

本発明は、チオクロマン誘導体を非常に高い光学純度で供給できることから、医薬・農薬の開発と生産に有用であり、産業上の利用可能性がある。
Since the thiochroman derivative can be supplied with very high optical purity, the present invention is useful for the development and production of pharmaceuticals and agricultural chemicals, and has industrial applicability.

Claims (2)

下記式(1)で示される触媒を用いて下記式(2)で示されるチオクロマン誘導体を合成する方法。
(ここでRおよびRは、おのおの独立して、H、Me、Et、tBu、ハロゲン、アルコキシ、又はニトロ基である。RおよびRは、いずれ位置に複数結合していてもよい。)
A method of synthesizing a thiochroman derivative represented by the following formula (2) using a catalyst represented by the following formula (1).
(Wherein R 1 and R 2 are each independently H, Me, Et, tBu, halogen, alkoxy, or nitro group. R 1 and R 2 may be bonded in plural at any position. .)
下記式(2)で示されるチオクロマン誘導体。
(ここでRおよびRは、おのおの独立して、H、Me、Et、tBu、ハロゲン、アルコキシ、又はニトロ基である。RおよびRは、いずれ位置に複数結合していてもよい。)
A thiochroman derivative represented by the following formula (2).
(Wherein R 1 and R 2 are each independently H, Me, Et, tBu, halogen, alkoxy, or nitro group. R 1 and R 2 may be bonded in plural at any position. .)
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JP2015051955A (en) * 2013-09-09 2015-03-19 国立大学法人 千葉大学 Optically active asymmetric bisindole compound and method for manufacturing the same
CN105924425A (en) * 2016-04-29 2016-09-07 浙江师范大学 Preparation method of dihydrothiochroman derivative
CN111606924A (en) * 2020-06-03 2020-09-01 成都大学 Chiral thiopyranoindolophenylthiolsulfone derivatives and preparation method thereof

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Publication number Priority date Publication date Assignee Title
JP2015051955A (en) * 2013-09-09 2015-03-19 国立大学法人 千葉大学 Optically active asymmetric bisindole compound and method for manufacturing the same
CN105924425A (en) * 2016-04-29 2016-09-07 浙江师范大学 Preparation method of dihydrothiochroman derivative
CN111606924A (en) * 2020-06-03 2020-09-01 成都大学 Chiral thiopyranoindolophenylthiolsulfone derivatives and preparation method thereof

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