Heterocyclic Natural Products Synthesis Using Reactive Meleimides that effect Asymmetric Cycloaddition with Unreactive Dienes

使用反应性蜜酰亚胺合成杂环天然产物，该反应性蜜酰亚胺与非反应性二烯进行不对称环加成

• 批准号: 03670995
• 负责人: ARAI Yoshitsugu
• 金额: $ 1.22万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670995/
• 关键词: Sulfinyl maleimide; Diels-Alder reaction; Acyliminium addition; Chiral synthesis; (+)-Indolizidine; (+)-Trachelanthamidine; (+)-Elaeokanines A and C; Diastereoselective; スルフィニルマレイミド; キラル合成; フラン; (+)ーインドリチジン; (+)ートラキランタミジン; ディ-ルス・アルダ-反応; ヨウ化サ

Enantiomerically pure N-substituted alpha-(2-exo-hydroxy-10-bornylsulfinyl)maleimides have been synthesized diastereoselectively. N-3-butynyl-, N-TBDMS- and N-p-methoxybenzyl maleimides obtained undergo Diels-Alder reactions with cyclopentadiene as well as furan to give the corresponding cycloadducts with a high degree of diastereoselectivity.The Diels-Alder adduct derived from the N-butynyl maleimide and cyclopentadiene was transformed into a gamma-hydroxy lactam via regioselective reduction followed by desulfinylation. The gamma-hydroxy lactam obtained has been further transformed into (+)-indolizidine and (+)-trachelanthamidine by diastereoselective N- acyliminocyclization and retro Diels-Alder reaction (flash vacuum pyrolysis) as key steps.By the similar methodology, the Diels-Alder adduct derived from the N-TBDMS maleimide and cyclopentadiene has been converted into (+)-elaeokanines A and C.The Diels-Alder adduct with the N-p-methoxybenzyl maleimide and furan was transformed into a chiral gamma-hydroxy lactam which has been further converted into a useful, chiral synthetic precursor, 5-substituted3- pyrrolin-2-one and 2,5-cis-disubstituted pyrrolidine derivative through diastereoselective N-acylimino addition and retro Diels-Alder reaction that was effected by heating in xylene.

非对映选择性地合成了N-取代α-（2-外羟基-10-乙酰基亚磺酰基）马来酰亚胺。N-3-丁炔基-、N-TBDMS-和N-对甲氧基苄基马来酰亚胺分别与环戊二烯和呋喃发生Diels-Alder反应，得到具有高度非对映选择性的环加成物，然后通过区域选择性还原和双烯酰化反应，将环加成物转化为γ-羟基内酰胺。通过非对映选择性的N-酰基亚氨基环化和逆Diels-Alder反应，将γ-羟基内酰胺进一步转化为（+）-中氮茚和（+）-络石脒（闪速真空热解）作为关键步骤。通过类似的方法，衍生自N-TBDMS马来酰亚胺和环戊二烯的Diels-Alder加合物已经转化为（+）-油桐碱A和C。甲氧基苄基马来酰亚胺和呋喃转化为手性γ-羟基内酰胺，其通过非对映选择性N-酰基亚氨基加成和通过在二甲苯中加热进行的逆Diels-Alder反应进一步转化为有用的手性合成前体5-取代的3-吡咯啉-2-酮和2，5-顺式-二取代的吡咯烷衍生物。

项目成果

T.Takahashi,A Fujii,T.Sugita,T.Hagi,K.Kitano,Y.Arai,T.Koizumi: "Asymmetric 1,3-Dipolar Cycloaddition of Chiral Sulfinylethenes with 1-Methy1-3-oxido-pyridinium and Some Nitrones" Tetrahedron:Asymmetry. 2. 1379-1390 (1991)

T.Takahashi、A Fujii、T.Sugita、T.Hagi、K.Kitano、Y.Arai、T.Koizumi：“手性亚磺酰乙烯与 1-甲基 1-3-氧化吡啶鎓等的不对称 1,3-偶极环加成反应

Y.Arai,T.Koizumi: "Synthesis and Asymmetric DielsーAlder Reactions of Chiral α,βーunsaturated Sulfoxides bearing a2ーexoーHydroxyー10ーbornyl Group as an Efficient Ligand on the Sultur Center" Reviews on Heteroatom Chemistry.

Y.Arai，T.Koizumi：“带有a2-exo-Hydroxy-10-bornyl Group作为Sultur Center上的有效配体的手性α,β-不饱和亚砜的合成和不对称Diels-Alder反应”杂原子化学评论。

Y.Arai,A.Fujii,T.Ohno,T.Koizumi: "Stereocontrol in Intermolecular Nucleophilc Addition to N-Acyliminium Ion Directed by a Bicyclo[2.2.1]heptene or 7-Oxabicyclo[2.2.1]heptene Group.A Novel Route to 5-Substituted 3-pyrrolin-2-ones of High Optical Purity" Ch

Y.Arai、A.Fujii、T.Ohno、T.Koizumi：“双环[2.2.1]庚烯或 7-氧杂双环[2.2.1]庚烯基团引导的 N-酰亚胺离子分子间亲核加成的立体控制。A

Y ARAI,M MATSUI,T KOIZUMI,M SHIRO: "Powerful Dienophoes for Asymmetric Diels-Alder Reactions:α-(2-exo-Hydroxy-10-bornylsulfinyl)maleimides" Journsl of Organic Chemistry. 56. 1983-1985 (1991)

Y ARAI、M MATSUI、T KOIZUMI、M SHIRO：“用于不对称 Diels-Alder 反应的强大二烯磷：α-(2-exo-Hydroxy-10-bornylsulfinyl)maleimides”《有机化学杂志》56。1983-1985 (1991)。

荒井 謙次: "新規光学活性α.β-不飽和スルホキシドの合成と不在付加反応への展開" 薬学研究の進歩. 7. 74-86 (1991)

Kenji Arai：“新型光学活性 α.β-不饱和亚砜的合成及其在缺席加成反应中的发展”《药物研究进展》7. 74-86 (1991)。