Synthesis of α,α-Difluorinated Phosphonate pSer/pThr Mimetics via Rhodium-Catalyzed Asymmetric Hydrogenation of ß-Difluorophosphonomethyl α-(Acylamino)acrylates.
Org Lett
; 20(11): 3278-3281, 2018 06 01.
Article
in En
| MEDLINE
| ID: mdl-29782177
ABSTRACT
A novel and facile synthetic strategy for α,α-difluorinated phosphonate mimetics of phosphoserine/phosphothreonine utilizing rhodium-catalyzed asymmetric hydrogenation was developed. The dehydrogenated substrate ß-difluorophosphonomethyl α-(acylamino)acrylates were first prepared from protected serine/threonine followed by asymmetric hydrogenation using the rhodium-DuPhos catalytic system to generate the chiral center(s). These important phosphonate building blocks were successfully incorporated into phosphatase-resistant peptides, which displayed similar inhibition to the 14-3-3 ζ protein as the parent pSer/pThr peptides.
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En
Year:
2018
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Article