A Bioreactor Manufactured for Oragnic Syntheses using Non-aqueous Solvents and Its Application

非水溶剂有机合成生物反应器及其应用

• 批准号: 07558089
• 负责人: TANAKA Kazuhiko
• 金额: $ 8.26万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07558089/
• 关键词: bioreactor; heptahalicenediol; enantiomer; helicity; optical resolution; clathrate; ヘリシティ; リパーゼPS; ラセミ体; 比旋光度; リパーゼCAL; 不斉反応

1. Synthesis of Bis (hydroxymethyl) [7] thiaheterohelicene :We designed a thiaheterohelicene with two hydroxy groups at the terminal aromatic nuclei and synthesized racemic 2,13-bis (hydroxymethyl) dithieno [3,2-e : 3', 2'-e'] benzo [1,2-b : 4,3-b'] bis [1] benzothiophene from readily available 1-hydroxymethyl [1,2-b : 4,3-b'] benzo-dithiophene.2. Molecular Structure and Crystal Packing of Bis (hydroxymethyl) [7] thia-heterohelicene :The molecular structure and the crystal packing of racemic [7] helicenediol was determined by X-ray analysis. The [7] helicenediol has C_2 symmetry, and ethanol molecule was included in the crystals in a ratio [7] helicenediol : ethanol=1 : 1 by intermolecular hydrogen bonds. In the crystal cell, the helicenes possessing same helicity (P or M) are aligned in a stacking column along b axis of the crystal.3. Optical Resolution of Helicenediol by Lipase-catalyzed Transesterification :The reaction of racemic [7] helicenediol (100mg) with the lipase from Pseudo … More monas cepacia (Amano PS,2.99g) in dichloromethane (100ml) in the presence of molecular sieves 4A (4.37g) at room temperature was terminated close to the 50% esterification point (25h), giving (P) - (+) - [7] helicenediol (44.7mg, 45% yield) in 98% ee and the corresponding monoacetate (40.9mg, 38% yield) and diacetate (15.1mg, 13% yield) which were readily separated by silica gel chromatography. The rotational value of (P) - (+) - [7] helicenediol was [alpha] _D +1973 (c0.055, CHCl_3). Hydrolysis of the monoacetate by NaOH in methanol gave (M) - (-) - [7] helicenediol with 80% ee and the diacetate gave the same enantiomer with 95% ee. In contrast, the transesterification of the racemic [7] helicenediol (100mg) with the lipase from Candida antarctica (Nova CAL, 0.5g) gave (M) - (-) - bis (hydroxymethyl) [7] thiaheterohelicene (43.7mg, 44%yield) with 92% ee and the corresponding monoacetate (57.8mg, 53% yield) and diacetate (3.4mg, 3% yield). The rotational value of (M) - (-) - [7] helicenediol was [alpha]_D -1965 (c0.050, CHCl_3). Less

1. 双（羟甲基）[7]硫杂螺旋烯的合成：我们设计了末端芳香核上有两个羟基的硫杂螺旋烯，并合成了外消旋2,13-双（羟甲基）二噻吩并[3,2-e : 3', 2' -e']苯并[1,2-b：4,3-b']双[1]苯并噻吩，可从现成的1-羟甲基[1,2-b : 4,3-b']苯并二噻吩。2.双(羟甲基)[7]硫杂杂螺旋烯的分子结构和晶体堆积:外消旋[的分子结构和晶体堆积] [7]螺旋烯二醇通过X射线分析确定 [7]螺旋烯二醇具有C_2对称性，并且乙醇分子以一定比例包含在晶体中。 [7] 螺烯二醇：乙醇=1：1 在晶胞中，具有相同螺旋度（P或M）的螺烯沿着晶体的b轴排列在堆积柱中。 3．脂肪酶催化的酯交换反应：外消旋 [7] 螺旋烯二醇 (100 毫克) 与来自假单胞菌 (monas cepacia) 的脂肪酶的反应(Amano PS，2.99g)在二氯甲烷(100ml)中在分子筛4A(4.37g)存在下在室温下在接近50％酯化点处终止(25h)，得到(P)-(+)-[7 ] 98% ee 中的螺旋烯二醇（44.7mg，产率 45%）和相应的单乙酸酯（40.9mg， 38％产率)和二乙酸酯(15.1mg，13％产率)通过硅胶色谱很容易分离。(P)-(+)-[7]螺烯二醇的旋转值为α_D+1973(c0.055)。在甲醇中用NaOH水解单乙酸酯得到(M)-(-)-[7]螺烯二醇。 80% ee 和二乙酸酯产生相同的对映异构体（95% ee）。相比之下，外消旋[7]螺旋烯二醇（100mg）与来自南极假丝酵母（Nova CAL，0.5g）的脂肪酶发生酯交换反应，得到（M）-（-）。 ) - 双(羟甲基) [7] 硫杂螺旋烯 (43.7mg, 44% 产率) 92％ee和相应的单乙酸酯(57.8mg，53％收率)和二乙酸酯(3.4mg，3％收率)。(M)-(-)-[7]螺烯二醇的旋转值为α_D -1965( c0.050，CHCl_3)。

项目成果

Kazuhiko Tanaka: "Synthesis and Crystal Structure of Functionalized Chiral [7] Thiaheterohelicenes" Enantiomer. 1997(in press.). (1997)

Kazuhiko Tanaka：“功能化手性 [7] 硫杂螺烯”对映体的合成和晶体结构。

Kazuhiko Tanaka: "A Novel Route to Disubstituted [7] Thiaheterohelicene via Biaryl- and Cabonyl- Coupling Reactions" Tetrahedron Letters. 38 (in press). (1997)

Kazuhiko Tanaka：“通过联芳基和羰基偶联反应实现双取代 [7] 硫杂螺旋烯的新途径”四面体快报。

Kazuhiko Tanaka: "Synthesis and Crystal Strustal of Chiral Bifunctional Helicenes with π-Deficient Pyridine and π-Excessive Thiophene Units" Tetrahedron Letters. 37. 5925-5928 (1996)

Kazuhiko Tanaka：“具有 π 缺陷吡啶和 π 过量噻吩单元的手性双功能螺旋烯的合成和晶体支撑”四面体快报 37。 5925-5928 (1996)

Osuga Hideji: "Practical Synthesis of Optically Pure Bifunctionalized Heterohelicenes" Bulletin of the Chemical Society of Japan. 70(in press.). (1997)

Osuga Hideji：“光学纯双官能化杂螺烯的实用合成”日本化学会通报。

Kazuhiko Tanaka: "Complexation with Helical Molecules : Helical Crystal Structure of Bis (hydroxymethyl) [7] thiaheterohelicene and Ethanol Clathrate" Journal of the Chemical Society, Chem. Commun.1873-1874 (1995)

Kazuhiko Tanaka：“与螺旋分子的络合：双（羟甲基）[7]硫杂螺旋烯和乙醇包合物的螺旋晶体结构”化学会杂志，化学。