Total synthesis of Resolvin E1 |
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Authors: | Melissa AllardKeith Barnes Xuemei ChenYiu-Yin Cheung Bryan DuffyCharles Heap John InthavongsayMatthew Johnson Ravi KrishnamoorthyChris Manley Stephan SteffkeDeepu Varughese Ruifang WangYi Wang CE Schwartz |
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Institution: | a AMRI, 21 Corporate Circle, Albany, NY 12212, USA b Resolvyx Pharmaceuticals, 222 Third Street, Cambridge, MA 02142, USA |
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Abstract: | The enantioselective total synthesis of Resolvin E1 (RvE1), a naturally occurring small molecule mediator of inflammation resolution, is reported. Two routes are presented, both modular and convergent in nature, with an excellent control of all stereocenters. The C12- and C18-hydroxy groups are derived from (S)-glycidol while the C5-hydroxy group is installed via enantioselective reduction of a ketone precursor. Both the cis-alkenes are introduced with excellent control by the reduction of a late-stage bis-alkyne intermediate. The synthetic disconnections are very amenable to analog preparation, and further modifications to the chemistry have allowed for scale-up and First in Man testing of this novel pro-resolution molecule. |
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Keywords: | Resolvin E1 Inflammation resolution Total synthesis Enantioselective synthesis Takai and Sonogashira couplings |
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