- Effect of Transition Metals on Chemodivergent Cross-Coupling of Acrylamides with Vinyl Acetate via C-H Activation
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A novel chemodivergent cross-coupling of acrylamides and vinyl acetates has been realized via metal-catalyzed vinylic C-H activation. The selective olefinic C-H vinylation and alkenylation reaction was examined with a variety of differently functionalized acrylamides. The reaction efficiently generates a range of highly synthetically valuable butadienes with good functional group tolerance in good to moderate yields. A possible catalytic reaction mechanism involving the chelation-assisted olefinic C-H activation via an acetate-assisted deprotonation pathway is proposed.
- Logeswaran, Ravichandran,Jeganmohan, Masilamani
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supporting information
p. 5679 - 5683
(2021/08/03)
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- Novel 2,7-dialkyl-substituted 5(S)-amino-4(S)-hydroxy-8-phenyl- octanecarboxamide transition state peptidomimetics are potent and orally active inhibitors of human renin
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The action of renin is the rate-limiting step of the renin-angiotensin system (RAS), a key regulator of blood pressure. Effective renin inhibitors directly block the RAS entirely at source and, thus, may provide a vital weapon for hypertension therapy. Our efforts toward identifying novel small-molecule peptidomimetic renin inhibitors have resulted in the design of transition-state isosteres such as 1 bearing an all-carbon 8-phenyl-octanecarboxamide framework. Optimization of the extended P3 portion of 1 and extensive P2′ modifications provided analogues with improved in vitro potencies in the presence of plasma. X-ray resolution of rh-renin/38a in the course of SAR work surprisingly unveiled the exploitation of a previously unexplored pocket (S3sp) important for strong binding affinities. Several inhibitors demonstrated oral efficacy in sodium-depleted marmosets. The most potent, 38a, induced dose-dependently a pronounced reduction in mean arterial blood pressure, paralleled by complete blockade of active plasma renin, up to 8 h post-dose. Oral bioavailability of 38a was 16% in marmosets.
- G?schke, Richard,Stutz, Stefan,Rasetti, Vittorio,Cohen, Nissim-Claude,Rahuel, Joseph,Rigollier, Pascal,Baum, Hans-Peter,Forgiarini, Peter,Schnell, Christian R.,Wagner, Trixie,Gruetter, Markus G.,Fuhrer, Walter,Schilling, Walter,Cumin, Frédéric,Wood, Jeanette M.,Maibaum, Jürgen
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p. 4818 - 4831
(2008/03/13)
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- Lipase catalyzed aminolysis of ethyl propiolate and acrylic esters. Synthesis of chiral acrylamides
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Candida cylindracea lipase is a useful catalyst for the preparation of propiolamides. Candida antarctica lipase efficiently catalyzes the aminolysis of different acrylic esters and aliphatic amines; if racemic amines are used, the corresponding optically active acrylic amide is obtained in moderate-high enantiomeric excess.
- Puertas,Brieva,Rebolledo,Gotor
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p. 4007 - 4014
(2007/10/02)
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