利用銠金屬催化3–乙氧基及3–氧代–4–芳基–1,2,5–噻二唑1,1–二氧化物之不對稱烯丙基化合成含四級碳之α-氨基酸
No Thumbnail Available
Date
2018
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
本論文敘述以不同的烯丙基三氟硼酸鉀鹽試劑3與3–乙氧基–4–芳基–1, 2, 5–噻二唑1, 1–二氧化物1及3–氧代–4–芳基–1, 2, 5–噻二唑1, 1–二氧化物2進行不對稱1, 2-加成反應，成功地合成出一系列的掌性高烯丙胺化合物6，產率最高達到92%，鏡像超越值最高99% ee，非鏡像異構物比例最高達到20:1；以及得到掌性高烯丙胺化合物8，產率最高達到97%，最高鏡像超越值>99.5% ee。
使用加成產物8s，將主架構的五環結構開環得到具有掌性中心四級碳之α-胺基酸衍生物51c，再經由多步反應後，可合成出藥物BMS-561392之鏡像化合物55b。
This thesis describes the enantioselective addition of a variety of potassium allyl trifluoroborates 3 to 3-ethoxy-4-aryl-1,2,5-thiadiazole-1,1-dioxides 1 and 3-oxo-4-aryl-1,2,5-thiadiazole-1,1-dioxides 2, providing the corresponding adducts 6 in up to 92% yield with up to 99% ee and up to 20:1 diastereomeric ratio and 8 in up to 92% yield with 99% ee. The method is useful in offering efficient and convenient synthesis of quaternary α-amino acids, witnessing the synthetic utility in the preparation of ent–BMS-561392 (55a), which is an inhibitor of tumor necrosis factor-α (TNF-α) converting enzyme for the potential treatment of rheumatoid arthritis.
This thesis describes the enantioselective addition of a variety of potassium allyl trifluoroborates 3 to 3-ethoxy-4-aryl-1,2,5-thiadiazole-1,1-dioxides 1 and 3-oxo-4-aryl-1,2,5-thiadiazole-1,1-dioxides 2, providing the corresponding adducts 6 in up to 92% yield with up to 99% ee and up to 20:1 diastereomeric ratio and 8 in up to 92% yield with 99% ee. The method is useful in offering efficient and convenient synthesis of quaternary α-amino acids, witnessing the synthetic utility in the preparation of ent–BMS-561392 (55a), which is an inhibitor of tumor necrosis factor-α (TNF-α) converting enzyme for the potential treatment of rheumatoid arthritis.
Description
Keywords
一價銠金屬, 不對稱烯丙基化反應, 掌性雙環 [2.2.1] 雙烯配基, Rhodium (I), Enantioselective Allylation, Chiral Bicyclo [2.2.1] Diene Ligands