67951-43-3Relevant articles and documents
Ketonization of 2-hydroxy-2,4-pentadienoate by 4-oxalocrotonate tautomerase: Implications for the stereochemical course and the mechanism
Lian, Huiling,Whitman, Christian P.
, p. 7978 - 7984 (1993)
4-Oxalocrotonate tautomerase (EC 5.3.2-; 4-OT), an enzyme involved in the bacterial degradation of catechol to intermediates in the Krebs cycle, catalyzes the ketonization of 2-hydroxymuconate (1) to the α,β-unsaturated ketone (E)-2-oxo-3-hexenedioate (2). Kinetic studies on 4-OT suggest that the enzyme is an isomerase and catalyzes the transformation of (E)-2-oxo-4-hexenedioate (3) to 2 through the intermediacy of 1. Isomerases can proceed by either a "one-base" or a "two-base" mechanism. The overall stereochemical course of an isomerase reaction can be used to distinguish between these two mechanisms. The stereochemical analysis of the 4-OT reaction presents a challenge because the proposed substrate, 3, cannot be synthesized or isolated. This complication is circumvented by utilizing strategies based on the expected stereospecific partitioning of 1 and related dienols in 2H2O. It was previously determined that 4-OT ketonizes 1 to (5S)-[5-2H]2. Because it was not possible to obtain sufficient quantities of [3-2H]3 for stereochemical analysis, an alternate substrate for 4-OT, 2-hydroxy-2,4-pentadienoate (4), was used in order to determine the stereochemistry of deuterium incorporation at the 3-position. The dienol 4 is ketonized rapidly by 4-OT to the β,γ-unsaturated ketone 2-oxo-4-pentenoate (5) before a much slower conversion to its α,β-isomer, 2-oxo-3-pentenoate (6). This behavior allows for the accumulation of 5 in solution. In order to assign the stereochemistry, the 4-OT-catalyzed ketonization of 4 was performed in 2H2O. The product, [3-2H]5, was trapped with NaBH4, processed to [3-2H]malate by chemical and enzymatic degradative procedures, and analyzed by 1H NMR spectroscopy. It was concluded that 4-OT ketonizes 4 stereoselectively to (3R)-2-oxo-[3-2H]-4-pentenoate. This result and the previous stereochemical finding indicate that the isomerization of 3 to 2 is predominantly a suprafacial process suggesting that 4-OT proceeds by a one-base mechanism.
Generation of a Heteropolycyclic and sp3-Rich Scaffold for Library Synthesis from a Highly Diastereoselective Petasis/Diels–Alder and ROM–RCM Reaction Sequence
Flagstad, Thomas,Azevedo, Carlos M. G.,Troelsen, Nikolaj S.,Min, Geanna K.,Macé, Yohan,Willaume, Anthony,Guilleux, Rachel,Velay, Mélanie,Bonnet, Karine,Morgentin, Remy,Nielsen, Thomas E.,Clausen, Mads H.
, p. 1061 - 1076 (2019/01/04)
Efficient access to diverse screening compounds with desirable, lead-like properties can be a bottleneck in early drug discovery and chemical biology. Herein we present an efficient, rapid route to three structurally distinct classes of compounds (A–C) from a single precursor, which in turn is available through a one-pot Petasis 3-component reaction/Diels–Alder cascade reaction. We demonstrate the versatility of the approach through the synthesis of 35 exemplary compounds from the three classes, as well as by the production of 2188 final compounds, which have been included in the Joint European Compound Library of the European Lead Factory.
MICROORGANISMS FOR PRODUCING 4C-5C COMPOUNDS WITH UNSATURATION AND METHODS RELATED THERETO
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, (2016/01/25)
The invention provides a non-naturally occurring microbial organism having a butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol, pathway. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in a pathway. The invention additionally provides a method for producing butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol,. The method can include culturing a butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol-producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding a pathway enzyme in a sufficient amount, and under conditions and for a sufficient period of time to produce butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol.