Development of Antitumor Compounds Using the Chiral Benzaldehyde

使用手性苯甲醛开发抗肿瘤化合物

• 批准号: 09470484
• 负责人: HANAOKA Miyoji
• 金额: $ 6.91万
• 依托单位: Kanazawa 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-09470484/
• 关键词: chiral benzaldehyde; styryllactone; chiral aldol reaction; stereoselective reaction; chiral synthesis; lactone structure; antitumor compound; 不斉ベンズアルデヒド; ゴニオヘプトライド; 1,3-双極子環状付加反応; ニッコマイシン; ゴニオフピロン; チオエステル; タキソ-ル; 立体選択反応

1. Chirai aldol reaction of the chiral benzaldehyde with silyl ketene acetals afforded anti-aldol products with highly stereoselectivity. Thus, chirality of the chiral benzaldehyde was effectively transformed to a chiral carbon chain.2. Aldol reaction of the chiral benzaldehyde with a titanium enolate derived form a thioester gave stereoselectively an anti-aldol product.3. Common synthetic intermediate having four continuous asymmetric carbons was synthesized in highly stereoselective manner and highly optical yield from the chiral benzaldehyde through twice aldol reactions. Total synthesis of styryllactones having a 5-membered lactone, goniofufurone, goniobutenolide A and B was achieved.4. Conversion of a 5-membered lactone to a 6-membered lactone through a lactol was developed. According to this method, styryllactones having a 6-membered lactone, goniodiol, goniotriol, 8-acetylgoniotriol, altholactone, and 9-deoxygoniopypyrone were synthesized.5. Chiral total synthesis of goniofupyrone was succeeded. This synthesis established the structure of goniofupyrone including absolute stereochemistry and revised the previously proposed structure.6. The structure of gonioheptolide A was revised by its synthesis from goniofupyrone. The proposed 8-membered lactone structure was found to be incorrect.7. Amino acid part of AI-77B, an antiulcerogenic antibiotic, and AI-77B analogue were synthesized from the chiral benzaldehyde.8. 1,3-Dipolar cycloaddition of chiral nitrons, derived form the chiral benzaldehyde, with olefins gave stereoselectively cis-3,5-disubstituted isoxazolidines.

1.通过手性苯甲醛与硅基烯酮缩醛的手性羟醛缩合反应，得到了高立体选择性的反式羟醛缩合产物。从而有效地将手性苯甲醛的手性转化为手性碳链.手性苯甲醛与硫酯衍生的烯醇化钛进行羟醛缩合反应，立体选择性地得到了反式羟醛缩合产物.以手性苯甲醛为原料，通过两次羟醛缩合反应，以高立体选择性和高光学产率合成了具有四个连续不对称碳原子的常用合成中间体。全合成了具有5元内酯的苯乙烯基内酯、goniofurone、goniobutenetrine A和B.开发了通过内缩醛将5元内酯转化为6元内酯。根据该方法，合成了具有6元内酯的苯乙烯基内酯、角碘醇、角碘三醇、8-乙酰基角碘三醇、altholactone和9-脱氧角碘吡喃酮。成功地实现了Goniofupyrone的手性全合成。该合成建立了goniofupyrone的结构，包括绝对立体化学，并修订了以前提出的结构。通过从Goniofupyrone合成Gonioheptolide A，修正了其结构。建议的8元内酯结构被发现是不正确的。7.从手性苄叉丙酮合成了抗溃疡抗生素AI-77 B的氨基酸部分及其类似物。由手性苯甲醛衍生的手性硝子与烯烃进行1，3-偶极环加成反应，立体选择性地合成了顺式-3，5-二取代异恶唑烷。

项目成果

Chisato Mukai: "Revised Structure of Gonioheptolide A" Chem,Pharm.Bull.47・1. 131-132 (1999)

向井千里：“七角庚内酯 A 的修订结构” Chem,Pharm.Bull.47・1 (1999)。

Chisato Mukai: "New Approach to AI-77B : Stereoselective Conversion of a Potential Precursor of the Amino Acid Side Chain"J. Chem. Soc., Perkin Trans. 1. 913-917 (1997)

Chisato Mukai：“AI-77B 的新方法：氨基酸侧链潜在前体的立体选择性转化”J。

Chisato Mukai: "Revised Structure of Gonioheptolide A"Chem. Pharm. Bull.. 47. 131-132 (1999)

Chisato Mukai：“Gonioheptolide A 的修订结构”化学。

MUKAI, Chisato: "Stereoselective Syntheses of (+)-Goniotriol, (+)-8-Acetyl-goniotriol, (+)-Goniodiol, (+)-9-Deoxygoniopypyrone, (+)-Altholactone and (-)-Goniofupyrone"J. Org. Chem.. 62・19. 6619-6626 (1997)

MUKAI，Chisato：“(+)-Gonitriol、(+)-8-Acetyl-goniotriol、(+)-Goniodiol、(+)-9-Deoxygoniopypyrone、(+)-Altholactone 和 (-)-Goniofupyrone 的立体选择性合成”化学杂志 62・19（1997）

Chisato Mukai: "Stereoselective Syntheses of (+)-Goniotrol,(+)-8-Acetylgoniotriol,(+)-goniodiol,(+)-9-Deoxygoniopypyrone,(+)-Altholactone,and (-)-Goniofupyrone" J.Org.Chem.62・19. 6619-6626 (1997)

Chisato Mukai：“(+)-Goniotrol、(+)-8-Acetylgoniotriol、(+)-goniodiol、(+)-9-Deoxygoniopyrone、(+)-Altholactone 和 (-)-Goniofupyrone 的立体选择性合成” J.有机化学62・19。6619-6626（1997）