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.
Department of Chemistry, New Chemistry Building, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Stefan
S
France
Daniel
D
Bernstein
Anthony
A
Weatherwax
Thomas
T
Lectka
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