Preparation and Exploitation of Versatile Cycloalkanoid Chiral Building Blocks

多功能环烷烃手性砌块的制备和开发

• 批准号: 09470479
• 负责人: OGASAWARA Kunio
• 金额: $ 4.03万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470479/
• 关键词: chiral building block; enzymatic synthesis; lipase; asymmetric synthesis; enantiomerization; enantiocontrolled synthesis; diastereocontrolled synthesis; natural product synthesis; シクロヘキサジエノン等価キラル素子; シクロペンタンジエノン等価キラル素子; コンベックス面選択的反応; 逆ディールス・アルダー

Two cycloalkanoid chiral building blocks, one serving as the synthetic equivalent of chiral cyclopentadienone and the other serving as the synthetic equivalent of chiral cyclohexadienone, have been prepared in enantiomerically pure forms in both enantiomeric forms by employing either enzymatic or catalytic enantioselective reaction. Both of the building blocks carry a common bicyclo[2.2.1]octane background in their molecules which serve as the protecting group for one of the enone olefin functionality. At the same time, this protecting group brings about molecular bias allowing diastereocontrolled modification of the other enone moiety of both of the chiral building blocks and may be removed under thermolysis conditions to regenerate the olefin protected by extrusion of cyclopentadiene through a retro-Diels-Alder reaction.A variety of biologically active natural products, more than fifty, were synthesized enantio- and diastereo-controlled mannor from these building blocks by employing a variety of reactions, such as Claisen rearrangement, [2,3]-Witting rearrangement, tandem-Diels-Alder-ene reaction, Diels-Alder reaction, Fischer indolization, Bailis-Hillman reaction, Heck and Sonogashira reactions, etc, which occurred diastereoselectively from the convex-face of the chiral building blocks owing to the biased-framework of the chiral building blocks.

两个环烷类手性结构单元，一个用作手性环己烯酮的合成等价物，另一个用作手性环己二烯酮的合成等价物，已经通过采用酶促或催化对映选择性反应以两种对映体形式以对映体纯的形式制备。这两种结构单元在其分子中携带共同的双环[2.2.1]辛烷背景，其用作烯酮烯烃官能团之一的保护基。同时，该保护基带来分子偏向，允许两种手性结构单元的另一个烯酮部分的非对映控制修饰，并且可以在热交换条件下除去，以通过逆Diels-桤木反应再生由环戊二烯挤出保护的烯烃。通过采用各种反应，如Claisen重排，[2，3]-Witting重排，串联Diels-Alder-烯反应，Diels-Alder反应，Fischer吲哚化，Bailis-Hillman反应，Heck和Sonogashira反应等，这些反应由于手性结构单元的偏置骨架而从手性结构单元的凸面发生非对映选择性反应。

项目成果

Hiroyuki Konno: "An Enantio-and Diastereoselective Synthesis of(-)-Isoretronecanol and(+)-Trachelanthamidine from a Meso Precursor"Heterocycles. 49. 33-37 (1998)

Hiroyuki Konno：“从内消旋前体中对映和非对映选择性合成（-）-异丙醇和（）-Trachelanthamidine”杂环。

Takashi Kamikubo: "Enantioconvergent Tactic for the Synthesis of (+)-Sporochnol A,the Fish Deterrent from the Caribbean Marine Alga Sporochnus boleanus" Enantiomer. 2(3/4). 297-301 (1997)

Takashi Kamikubo：“用于合成 ( )-Sporochnol A 的对映体聚合策略，该物质是加勒比海洋藻类 Sporochnus boleanus 的鱼类威慑剂”对映体。

Hiromi Nakashima: "A Stereocontrolled Route to(-)-Epibatidine Using a Chiral cis-Cyclohexadiene-1,4-diol Equivalent"Synlett. 1405-1406 (1999)

Hiromi Nakashima：“使用手性顺式环己二烯-1,4-二醇等效物实现 (-)-Epibatidine 的立体控制路线”Synlett。

Kou Hiroya: "Preparation of the Synthetic Equivalents of Chiral Cyclohexadienone and Cycloheptadienone : The Enantio- and Diastereo-controlled Synthesis of (-)-Clavularin B"Synlett. 529-532 (1999)

Kou Hiroya：“手性环己二烯酮和环庚二烯酮的合成等价物的制备：(-)-Clavularin B 的对映体和非对映体控制合成”Synlett。

Hiroyuki Konno: "Practical Preparation of Versatile Chiral Building Blocks"Synthesis. 1135-1140 (1999)

Hiroyuki Konno：“多功能手性构件的实际制备”合成。