[1,5]-Hydride Shift-Cyclization versus C(sp(2))-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4-and 1,5-Benzoxazepines

doi:10.3390/molecules25061265

	[1,5]-Hydride Shift-Cyclization versus C(sp(2))-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4-and 1,5-Benzoxazepines
	Vargane, Dora Szaloki 2,3; Toth, Laszlo 2,4; Buglyo, Balazs 2; Kiss-Szikszai, Attila 2; Mandi, Attila 2; Matyus, Peter 5; Antus, Sandor 2; Chen, Yinghan 1; Li, Dehai 1; Tao, Lingxue 6
刊名	MOLECULES
	2020-03-02
卷号	25 期号:6 页码:19
关键词	domino Knoevenagel-[1 5]-hydride shift-cyclization 1 4-benzoxazepine 1 5-benzoxazepine TDDFT-ECD calculation acetylcholinesterase inhibitory activity
DOI	10.3390/molecules25061265
通讯作者	Antus, Sandor(antus.sandor@science.unideb.hu) ; Kurtan, Tibor(kurtan.tibor@science.unideb.hu)
英文摘要	Domino cyclization reactions of N-aryl-1,4- and 1,5-benzoxazepine derivatives involving [1,5]-hydride shift or C(sp(2))-H functionalization were investigated. Neuroprotective and acetylcholinesterase activities of the products were studied. Domino Knoevenagel-[1,5]-hydride shift-cyclization reaction of N-aryl-1,4-benzoxazepine derivatives with 1,3-dicarbonyl reagents having active methylene group afforded the 1,2,8,9-tetrahydro-7bH-quinolino [1,2-d][1,4]benzoxazepine scaffold with different substitution pattern. The C(sp(3))-H activation step of the tertiary amine moiety occurred with complete regioselectivity and the 6-endo cyclization took place in a complete diastereoselective manner. In two cases, the enantiomers of the chiral condensed new 1,4-benzoxazepine systems were separated by chiral HPLC, HPLC-ECD spectra were recorded, and absolute configurations were determined by time-dependent density functional theory- electronic circular dichroism (TDDFT-ECD) calculations. In contrast, the analogue reaction of the regioisomeric N-aryl-1,5-benzoxazepine derivative did not follow the above mechanism but instead the Knoevenagel intermediate reacted in an SEAr reaction [C(sp(2))-H functionalization] resulting in a condensed acridane derivative. The AChE inhibitory assays of the new derivatives revealed that the acridane derivative had a 6.98 mu M IC50 value.
资助项目	National Research Development and Innovation Office[K-112951] ; National Research Development and Innovation Office[K-120181] ; EU - European Regional Development Fund[GINOP-2.3.2-15-2016-00008] ; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences[UNKP-19-4] ; New National Excellence Program of the Ministry for Innovation and Technology
WOS关键词	C-H BONDS ; CATALYTIC FUNCTIONALIZATION ; BECKMANN REARRANGEMENT ; ASYMMETRIC-SYNTHESIS ; HYDRIDE TRANSFER ; INHIBITORS ; ANALOGS ; ACID ; RING ; DERIVATIVES
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI
WOS记录号	WOS:000530248700008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280180]
专题	中国科学院上海药物研究所
通讯作者	Antus, Sandor; Kurtan, Tibor
作者单位	1.Ocean Univ China, Sch Med & Pharm, Chinese Minist Educ, Key Lab Marine Drugs, Qingdao 266003, Peoples R China 2.Univ Debrecen, Dept Organ Chem, POB 400, Debrecen 4002, Hungary 3.Univ Debrecen, Doctoral Sch Chem, Egyet Ter 1, Debrecen 4032, Hungary 4.Semmelweis Univ, Dept Organ Chem, Budapest 1094, Hungary 5.Semmelweis Univ, Fac Hlth & Publ Serv, Inst Digital Hlth Sci, Ferenc Ter 15, Budapest 1094, Hungary 6.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd,Zhang Jiang Hitech Pk, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Vargane, Dora Szaloki,Toth, Laszlo,Buglyo, Balazs,et al. [1,5]-Hydride Shift-Cyclization versus C(sp(2))-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4-and 1,5-Benzoxazepines[J]. MOLECULES,2020,25(6):19.
APA	Vargane, Dora Szaloki.,Toth, Laszlo.,Buglyo, Balazs.,Kiss-Szikszai, Attila.,Mandi, Attila.,...&Kurtan, Tibor.(2020).[1,5]-Hydride Shift-Cyclization versus C(sp(2))-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4-and 1,5-Benzoxazepines.MOLECULES,25(6),19.
MLA	Vargane, Dora Szaloki,et al."[1,5]-Hydride Shift-Cyclization versus C(sp(2))-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4-and 1,5-Benzoxazepines".MOLECULES 25.6(2020):19.