Bridge Functionalisation of Bicyclo[1.1.1]pentane Derivatives

被引:83
作者
Anderson, Joseph M. [1 ,2 ]
Measom, Nicholas D. [1 ]
Murphy, John A. [2 ]
Poole, Darren L. [1 ]
机构
[1] GlaxoSmithKline Med Res Ctr, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England
[2] Univ Strathclyde, Dept Pure & Appl Chem, WestCHEM, 295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
基金
英国工程与自然科学研究理事会;
关键词
bicyclopentanes; bioisosteres; propellanes; radical reactions; small-ring systems; RING CARBONYL-COMPOUNDS; AB-INITIO CALCULATIONS; PHOTOCHEMICAL-TRANSFORMATIONS; REACTIVITY; CHEMISTRY; ROUTE; PHOTOLYSIS; RESONANCE; CARBENES; KETONES;
D O I
10.1002/anie.202106352
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
"Escaping from flatland", by increasing the saturation level and three-dimensionality of drug-like compounds, can enhance their potency, selectivity and pharmacokinetic profile. One approach that has attracted considerable recent attention is the bioisosteric replacement of aromatic rings, internal alkynes and tert-butyl groups with bicyclo[1.1.1]pentane (BCP) units. While functionalisation of the tertiary bridgehead positions of BCP derivatives is well-documented, functionalisation of the three concyclic secondary bridge positions remains an emerging field. The unique properties of the BCP core present considerable synthetic challenges to the development of such transformations. However, the bridge positions provide novel vectors for drug discovery and applications in materials science, providing entry to novel chemical and intellectual property space. This Minireview aims to consolidate the major advances in the field, serving as a useful reference to guide further work that is expected in the coming years.
引用
收藏
页码:24754 / 24769
页数:16
相关论文
共 129 条
[1]   PHOTOLYSIS OF CYCLOBUTYL ARYL KETONES - EVIDENCE FOR INVOLVEMENT OF AN EXCITED-STATE CONFORMATIONAL EQUILIBRIUM IN THEIR PHOTOCONVERSION TO ARYL BICYCLO[1.1.1]PENTANOLS [J].
ALEXANDER, EC ;
ULIANA, JA .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1974, 96 (17) :5644-5646
[2]   PHOTOCHEMICAL-SYNTHESIS OF A TRICYCLO[2.2.0.02,5]HEXANE [J].
ALEXANDER, EC ;
ULIANA, J .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1976, 98 (14) :4324-4325
[3]  
ALEXANDER EC, 1978, TETRAHEDRON LETT, P1741
[4]  
[Anonymous], 2017, ANGEW CHEM, V129, P5778
[5]  
[Anonymous], 2005, ANGEW CHEM, V117, P5217
[6]  
[Anonymous], 2005, ANGEW CHEM, V117, P7598
[7]  
[Anonymous], 2020, Angew. Chem, V132, P3945
[8]  
[Anonymous], 1989, ANGEW CHEM, V101, P513
[9]  
[Anonymous], 2020, ANGEW CHEM, V132, P8302
[10]  
[Anonymous], 2015, ANGEW CHEM, V127, P15854