Synthesis of Optically Pure Enantiomers Using Chiral Ureas

使用手性脲合成光学纯对映体

基本信息

批准号：
03640438
负责人：
YAMADA Kazutoshi
金额：
$ 1.34万
依托单位：
CHIBA University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

Using Chiral urea derivatives, the following diastereoselective synthesis and a convenient separation of diastereomers by a conventional column chromatography were accomplished.(1) Diastereoselective aldol addition reaction using chiral acylureas; This method was applied to the two step synthesis of (+) Blastmaycinolactol.(2) Chiral carbodiimide as an effective chiral derivatizing agent; N,N'-bis[(s)-l-phenylethyl]- carbodiimide was found to be a very useful chiral derivatizing agent, which made an easy separation of diastereomers of alpha-amino acids and alpha-halo acids by a conventional column chromatography.(3) Highly enantioselective Aldol reaction using imidazolidinone as a new chiral Auxiliary; Aldol addition reaction of almost perfect stereo control (>99% diastereoselectivity) was developed.(4) Chiral hydantoin as a new dienophile for Diels-Alder Reaction; A new synthetic method of chiral exo-methylenehydantoin from chiral carbodiimides and alpha-ketoacids was established and the exo-methylenehydantoin thus obtained was applied for Diels-Alder reaction to prepare chiral bicyclic alpha-amino acid derivatives.(5) Conjugated addition reaction of alkylaluminum compounds to exo-methylenehydantoin; Mono and Double conjugated additions of aluminum reagents to exo-methylenehydantoin were found out and this two modes of addition was effectively controlled.(6) Three component coupling reaction carbodiimide, monomethyl maleate, and alcohol; This coupling afforded N-(aminocarbony)aspartates.(7) Asymmetric type II photocyclization of acrylylureas; It was found that the stereochemistry of the carbon atom where a hydrogen atom to be abstracted in type II photocyclization was retained to give a chiral beta-lactam.

利用手性脲衍生物，完成了以下非对映选择性合成，并通过常规柱色谱法方便地分离非对映异构体。(1)使用手性酰基脲的非对映选择性羟醛加成反应；将该方法应用于(+)Blastmaycinolactol的两步合成。(2)手性碳二亚胺作为有效的手性衍生剂； N,N'-双[(s)-l-苯乙基]-碳二亚胺被发现是一种非常有用的手性衍生剂，可以通过常规柱色谱轻松分离α-氨基酸和α-卤代酸的非对映异构体(3)使用咪唑烷酮作为新型手性助剂进行高度对映选择性的羟醛反应；发展了近乎完美的立体控制(>99%非对映选择性)的羟醛加成反应。(4)手性乙内酰脲作为Diels-Alder反应的新型亲双烯体；建立了手性碳二亚胺与α-酮酸合成手性外型亚甲基乙内酰脲的新方法，并将所得外型亚甲基乙内酰脲应用于Diels-Alder反应制备手性双环α-氨基酸衍生物。 (5)烷基铝的共轭加成反应外型亚甲基乙内酰脲的化合物；发现了铝试剂与外型亚甲基乙内酰脲的单共轭加成和双共轭加成，并有效控制了这两种加成方式。(6)碳二亚胺、马来酸单甲酯和醇的三组分偶联反应；该偶联得到N-(氨基羰基)天冬氨酸盐。(7)丙烯酰脲的不对称II型光环化；结果发现，碳原子的立体化学结构（其中在II型光环化中被夺取的氢原子被保留）得到手性β-内酰胺。