PMC

These groups include Glu490, Gln491, Glu493, Tyr494, Ile499 (backbone carbonyl), Asn500, Trp501 (backbone carbonyl), Thr502 (backbone carbonyl), Phe503 (backbone carbonyl), Lys690 (including backbone carbonyl), and Gly691 (backbone carbonyl) as suggested by Málnási-Csizmadia et al. []. The different colors represent three TMD simulations.

This figure shows the comparison between classical Grignard reaction and the Grignard reaction with alcohol as carbonyl surrogate. It clearly shows that the latter is both step and atom economical. More importantly, using alcohol as carbonyl surrogate has a broad potential for late-stage functionalizations in synthetic chemistry.

(A) Distances between the carbonyl oxygen (black), and amide hydrogen (red) of V96^CDK4 and the indoyl hydrogen and carbonyl oxygen of FAS, respectively. (B) Distances between the carbonyl oxygen (black) and amide hydrogen (red) of V96^CDK4 and the indoyl hydrogen and carbonyl oxygen of CRB, respectively. (C) Distances between the carbonyl oxygen (black) and amide hydrogen (red) of L83^CDK2 and the indoyl hydrogen and carbonyl oxygen of FAS, respectively. (D) Distances between the carbonyl oxygen (black) and amide hydrogen (red) of L83^CDK2 and the indoyl hydrogen and carbonyl oxygen of CRB, respectively. (E) Distances between the His95^CDK4 Nδ-H and the carbonyl oxygen of FAS (red) and CRB (black), respectively. (F) Distances between Lys89^CDK2 amine-N and the N+/C of FAS (red) and CRB (black), respectively.

Reactivity of bonds β to carbonyl. (a) Protons β to carbonyl are acidic because the conjugate base is resonance stabilized. The same resonance stabilization also renders C-C bonds β to carbonyl labile. B, generic base. (b) Protons α to carbonyl cannot be abstracted because the resulting conjugate base has no stable resonance forms. By the same logic, C-C bonds α to carbonyl cannot be broken or formed without cofactor involvement. (c) For glucose, C-C bond cleavage β to carbonyl would result in products with unequal numbers of carbon atoms, whereas for fructose it yields two trioses. In glycolysis, glucose is isomerized to fructose before it is cleaved. (d) Isomerization of citrate to isocitrate in the TCA cycle positions a hydroxyl group such that its subsequent oxidation to carbonyl enables production of α-ketoglutarate by C-C bond breakage β to carbonyl. (e) Decarboxylation of pyruvate requires C-C bond breakage α to carbonyl. This is enabled by addition of the cofactor thiamine to pyruvate’s carbonyl, which repositions the scissile C-C bond β to the ‘pseudocarbonyl’ (blue) of thiamine’s thiazolium ring.