Simultaneous preparation of four truncated analogues of discodermolide by fluorous mixture synthesis.
[structure: see text] Four truncated analogues of the natural product discodermolide were synthesized in a single synthetic sequence. Precursors bearing four different groups at C22, each with a unique fluorous p-methoxybenzyl substituent on the C17 hydroxy group, were mixed and taken through an nine-step sequence. Demixing by fluorous chromatography followed by deprotection and purification provided the individual analogues in 3-7% overall yields and with a savings of 24 synthetic steps. Fluorous mixture synthesis is recommended as a new technique to make multiple natural product analogues in a single multistep synthesis.
Curran
Dennis P
DP
Department of Chemistry and Center for Combinatorial Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. curran@pitt.edu
Furukawa
Takashi
T
D000473:Alkanes; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000302:isolation & purification; D002219:Carbamates; D002845:Chromatography; D005461:Fluorine; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000302:isolation & purification; D011753:Pyrones
D000473:Alkanes; D000970:Antineoplastic Agents; D002219:Carbamates; D006845:Hydrocarbons, Fluorinated; D007783:Lactones; D011753:Pyrones; D005461:Fluorine; C071229:discodermolide