Parallel synthesis of natural product-like polyhydroxylated pyrrolidine and piperidine alkaloids.
The preparation of natural product-like polyhydroxylated pyrrolidine and piperidine alkaloids using a combination of solid- and solution-phase organic synthesis is described. The key intermediates, enantiopure five- or six-membered tri-O-benzyl cyclic nitrones, were efficiently prepared on solid support from accessible chiral furanosides and pyranosides, respectively. The substituent diversity was achieved by a diastereoselective addition of a variety of Grignard reagents to the cyclic nitrones in solution-phase synthesis. All reaction steps and work-up procedures were modified to allow the use of automated equipment. A 36-membered demonstration library with three diversity elements (core, configuration, and substituent) was prepared in good yield and purity.
Chang
Yi-Fan
YF
The Genomics Research Center, Academia Sinica, No. 128, Academia Road Sec. 2, Nankang District, Taipei, 11529, Taiwan, ROC.
Guo
Chih-Wei
CW
Chan
Ting-Hao
TH
Pan
Yi-Wen
YW
Tsou
En-Lun
EL
Cheng
Wei-Chieh
WC
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry*; D006900:Hydroxylation; D009589:Nitrogen Oxides / Q000138:chemical synthesis / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry; D012996:Solutions; D014835:Volatilization
D000470:Alkaloids; D001688:Biological Products; D009589:Nitrogen Oxides; D010880:Piperidines; D011759:Pyrrolidines; D054852:Small Molecule Libraries; D012996:Solutions; C015388:nitrones; C032727:piperidine; C032519:pyrrolidine