Retro-aldol Mechanism Research Articles

Toward Closing the Gap between Hexoses and N-Acetlyhexosamines: Experimental and Computational Studies on the Collision-Induced Dissociation of Hexosamines.

Motivated by the fundamental difference in the reactivity of hexoses and N-acetylhexosamines under collision-induced dissociation (CID) mass spectrometry conditions, we have investigated the CID of two hexosamines, glucosamine (GlcN) and galactosamine (GalN), experimentally and computationally. Both hexosamines undergo ring-opening and then dissociate via the 0,2A and the 0,3A (0,3X) cross-ring cleavage channels. The preference for the ring-opening is similar to the behavior of N-acetylhexosamines and explains why the two anomers of the same sugar give the same mass spectrum. While the spectrum for GlcN is dominated by the 0,2A signal, the signal intensities for both 0,2A and the 0,3A (0,3X) dissociation channels are comparable for GalN, which allows GlcN and GalN to be distinguished easily. Calculations at MP2 level of theory indicate that this is related to the differences in the relative barrier heights for the 0,2A and the 0,3A (0,3X) cross-ring cleavage channels. This, in return, reflects the circumstance that the 0,2A cross-ring cleavage barriers are different for the two sugars, while the barriers of all other dissociation channels are comparable. While the mechanisms of the cross-ring dissociation channels of hexoses are well described using the retro-aldol mechanism in the literature, this study proposes a new mechanism for the 0,3A (0,3X) cross-ring cleavage of hexosamines that involves the formation of an epoxy intermediate or a zwitterionic intermediate.

Cationized Carbohydrate Gas-Phase Fragmentation Chemistry.

We investigate the fragmentation chemistry of cationized carbohydrates using a combination of tandem mass spectrometry, regioselective labeling, and computational methods. Our model system is D-lactose. Barriers to the fundamental glyosidic bond cleavage reactions, neutral loss pathways, and structurally informative cross-ring cleavages are investigated. The most energetically favorable conformations of cationized D-lactose were found to be similar. In agreement with the literature, larger group I cations result in structures with increased cation coordination number which require greater collision energy to dissociate. In contrast with earlier proposals, the B n -Y m fragmentation pathways of both protonated and sodium-cationized analytes proceed via protonation of the glycosidic oxygen with concerted glycosidic bond cleavage. Additionally, for the sodiated congeners our calculations support sodiated 1,6-anhydrogalactose B n ion structures, unlike the preceding literature. This affects the subsequent propensity of formation and prediction of B n /Y m branching ratio. The nature of the anomeric center (α/β) affects the relative energies of these processes, but not the overall ranking. Low-energy cross-ring cleavages are observed for the metal-cationized analytes with a retro-aldol mechanism producing the 0,2 A 2 ion from the sodiated forms. Theory and experiment support the importance of consecutive fragmentation processes, particularly for the protonated congeners at higher collision energies. Graphical Abstract ᅟ.

Density Functional Theory (DFT) study on the pyrolysis of cellulose: The pyran ring breaking mechanism

Pyran ring breaking is a key step for cellulose pyrolysis to produce small molecular products. Cellotriose was employed as the model compound of cellulose to explore the mechanism of pyran ring breaking based on Density Functional Theory (DFT). Four kinds of reaction mechanisms were studied: (1) directly breaking mechanism, (2) Retro–Diels–Alder mechanism, (3) C6OH assisted pinacol ring cleavage mechanism and (4) Retro–Aldol mechanism. The calculated results showed that pyran ring break via Retro–Aldol mechanism (with C3O formed) was kinetically favored over Retro–Diels–Alder mechanism (with C3C4 bond formed), followed by C6OH assisted pinacol ring cleavage mechanism, 2′+2′+2′ and 2+2+2 mechanism. Activation energies for both of the two-step mechanisms, Retro–Diels–Alder and Retro–Aldol, varied on the positions of CC bond and CO group formed. The results provided a better understanding on pyran ring breaking mechanism during cellulose pyrolysis.

Probing the ruthenium-catalyzed higher polyol hydrogenolysis reaction through the use of stereoisomers

Nine polyol stereoisomers ranging from three to six carbons in length were reacted under hydrogenolysis conditions (205–240 °C, 100 bar H2) over a Ru–C catalyst to better understand the reaction mechanism. Previous reports have postulated the retro-aldol mechanism as the main pathway leading to C–C scission. However, the retro-aldol mechanism was insufficient in explaining the product distribution of tetritols from pentitols, while the decarbonylation mechanism could explain the selectivity results of terminal C–C scission. Retro-aldol scission of internal C–C bonds was confirmed to occur by the tetritol product distribution from hexitols. Therefore, the presence or role of 3-keto and 4-keto intermediates had a negligible effect on the C–C hydrogenolysis of polyols when compared to aldehyde intermediates. The reaction rates of the polyols depended on the configuration of the polyol stereoisomers. The reactivity of the stereoisomers was correlated to the presence of erythro sequences of hydroxyl groups and was independent of the carbon chain length.

Mechanism for folate‐independent aldolase reaction catalyzed by serine hydroxymethyltransferase

Serine hydroxymethyltransferase catalyzes the cleavage of β-hydroxyamino acids into glycine and aldehydes in the absence of tetrahydrofolate. The enzyme accepts various β-hydroxyamino acids as the substrate of this reaction. The reaction rate varies depending on the substituent and stereochemistry at the Cβ atom: the erythro forms and the β-phenyl substituent are preferred over the threo forms and the β-methyl substituent, respectively. Although several mechanisms have been proposed, what determines the substrate preference remains unclear. We first performed quantum mechanical calculations to assess the validity of the reaction mechanisms. The results indicate that the retro-aldol mechanism starting with abstraction of the proton from the β-hydroxyl group is plausible. This also suggests that Cα-Cβ bond cleavage is the rate-limiting step. We next measured the dependence of the rate constants on temperature with four representative substrates and calculated the activation energies and pre-exponential factors from the Arrhenius plots. The activation energies of the erythro forms were lower than those of the threo forms. The β-phenyl substituent lowered the activation energy in the threo form, whereas it did not alter the activation energy but increased the pre-exponential factor in the erythro form. We present a unified model to explain the origin of the substituent and stereochemical preferences by combining the theoretical and experimental results. A possible biological role of the tetrahydrofolate-independent activity in thermophiles is also discussed.

ChemInform Abstract: The Retro-Aldol Mechanism in the Pyrolysis Kinetics of Primary, Secondary, and Tertiary β-Hydroxy Ketones in the Gas Phase.

ChemInform Abstract: The Retro-Aldol Mechanism in the Pyrolysis Kinetics of Primary, Secondary, and Tertiary β-Hydroxy Ketones in the Gas Phase.

Serine Hydroxymethyltransferase: Role of Glu75 and Evidence that Serine Is Cleaved by a Retroaldol Mechanism

Serine hydroxymethyltransferase (SHMT) catalyzes the reversible interconversion of serine and glycine with tetrahydrofolate serving as the one-carbon carrier. SHMT also catalyzes the folate-independent retroaldol cleavage of allothreonine and 3-phenylserine and the irreversible conversion of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate. Studies of wild-type and site mutants of SHMT have failed to clearly establish the mechanism of this enzyme. The cleavage of 3-hydroxy amino acids to glycine and an aldehyde occurs by a retroaldol mechanism. However, the folate-dependent cleavage of serine can be described by either the same retroaldol mechanism with formaldehyde as an enzyme-bound intermediate or by a nucleophilic displacement mechanism in which N5 of tetrahydrofolate displaces the C3 hydroxyl of serine, forming a covalent intermediate. Glu75 of SHMT is clearly involved in the reaction mechanism; it is within hydrogen bonding distance of the hydroxyl group of serine and the formyl group of 5-formyltetrahydrofolate in complexes of these species with SHMT. This residue was changed to Leu and Gln, and the structures, kinetics, and spectral properties of the site mutants were determined. Neither mutation significantly changed the structure of SHMT, the spectral properties of its complexes, or the kinetics of the retroaldol cleavage of allothreonine and 3-phenylserine. However, both mutations blocked the folate-dependent serine-to-glycine reaction and the conversion of methenyltetrahydrofolate to 5-formyltetrahydrofolate. These results clearly indicate that interaction of Glu75 with folate is required for folate-dependent reactions catalyzed by SHMT. Moreover, we can now propose a promising modification to the retroaldol mechanism for serine cleavage. As the first step, N5 of tetrahydrofolate makes a nucleophilic attack on C3 of serine, breaking the C2-C3 bond to form N5-hydroxymethylenetetrahydrofolate and an enzyme-bound glycine anion. The transient formation of formaldehyde as an intermediate is possible, but not required. This mechanism explains the greatly enhanced rate of serine cleavage in the presence of folate, and avoids some serious difficulties presented by the nucleophilic displacement mechanism involving breakage of the C3-OH bond.

Photochemische reaktionen—XXX : Norrish I spaltung von 3-dehydro-gibberellin a 1; beiträge zum retroaldol-mechanismus der alkali-katalysierten ga 1-epimerisierung

The n→π* photochemistry of saturated diterpenoid ketones of the 3-dehydro gibberellin A1 type 2 has been investigated whereas a NORRISH I type cleavage leading to the Δ3,4-unsaturated 3,4-seco 3-aldehyde 8 takes place in good yields. In the case of the photolysis of 2 in dioxane the solvent adduct 14 is formed as a minor product. The seco-aldehyde 8 represents a suitable key compound for a recyclization reaction sequence involving catalytic hydrogenation to the tetrahydro derivative 17 and subsequent alkali catalyzed ring A closure to dihydro GA1 (23) and dihydro pseudo GA1 (21) (16-epimers) in a 1:2 ratio confirming the retroaldol mechanism of the alkali catalyzed GA1 epimerization postulated by Cornforth. Similar, the secoaldehyde 8, after Wagner-Meerwein rearrangement, hydrogenation and alkali catalyzed ring closure via 18 and 20 leads to gibberellin C (29) and the 3-epi compound 28.

The epimerisation of 2-hydroxygibbane 1 ? 4a-lactones

Studies on the alkali-induced epimerisation at position 2 in 2-hydroxygibbane 1 → 4a lactones are reported. Mechanisms involving fission of the C-2-oxygen or C-2-hydrogen bonds are ruled out. The 2-methoxygibbane 1 → 4a lactones are not epimerised, indicating the abstraction of a proton from the 2-hydroxyl group as required in the originally suggested retro-aldol mechanism. Attempts to trap the intermediate were unsuccessful.