Performing the synthesis of a complex molecule on sequentially linked columns: toward the development of a "synthesis machine".
[reaction: see text] We describe the diastereoselective synthesis of a pharmaceutically active drug candidate via a column-based system. This methodology is complementary to classical solid-phase synthesis; individual columns are packed with resin-bound reagents and then linked in sequence and/or in parallel. In contrast to the traditional solid-phase approach, substrates are introduced in the mobile phase where they build up chemical complexity by percolating through the linked columns, ultimately eluting as the desired product.
France
Stefan
S
Department of Chemistry, New Chemistry Building, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Bernstein
Daniel
D
Weatherwax
Anthony
A
Lectka
Thomas
T
D002625:Chemistry, Organic / Q000295:instrumentation* / Q000379:methods*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure
D007093:Imidazoles; C422302:N-((2S)-2-mercapto-1-oxo-4-(3,4,4- trimethyl-2,5-dioxo-1-imidazolidinyl)butyl)-L-leucyl-N,3- dimethyl-L-Valinamide