7062-59-1

Upstream product

• 883581-66-6 tert-butyl 2-oxo-4-phenyl-3-butynoate 
• 536-74-3 phenylacetylene 
• 908600-38-4 tert-butyl 2-hydroxy-4-phenyl-3-butynoate 
• 1619-73-4 ethyl 2-oxo-4-phenylbut-3-ynoate 

Downstream Products

• 621-82-9 Cinnamic acid 

Relevant academic research and scientific papers

C-selective and diastereoselective alkyl addition to β,γ-alkynyl-α-imino esters with zinc(II)ate complexes

Since umpolung α-imino esters contain three electrophilic centers, regioselective alkyl addition with traditional organometallic reagents has been a serious problem in the practical synthesis of versatile chiral α-amino acid derivatives. An unusual C-alkyl addition to α-imino esters using a Grignard reagent (RMgX)-derived zinc(II)ate was developed. Zinc(II)ate complexes consist of a Lewis acidic [MgX]+moiety, a nucleophilic [R3Zn]- moiety, and 2[MgX2]. Therefore, the ionically separated [R3Zn]- selectively attacks the imino carbon atom, which is most strongly activated by chelation of [MgX]+. In particular, chiral β,γ-alkynyl-α-imino esters can strongly promote highly regio- and diastereoselective C-alkylation because of structural considerations, and the corresponding optically active α-quaternary amino acid derivatives are obtained within 5 minutes in high to excellent yields.

Inactivation of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor by 2-oxo-4-phenyl-3-butynoate

Macrophage migration inhibitory factor (MIF) is an important immunoregulatory protein that has been implicated in several inflammatory diseases. MIF also has a phenylpyruvate tautomerase (PPT) activity, the role of which remains elusive in these biological activities. The acetylene compound, 2-oxo-4-phenyl-3-butynoate (2-OPB), has been synthesized and tested as a potential irreversible inhibitor of its enzymatic activity. Incubation of the compound with MIF results in the rapid and irreversible loss of the PPT activity. Mass spectral analysis established that the amino-terminal proline, previously implicated as a catalytic base in the PPT-catalyzed reaction, is the site of covalent modification. Inactivation of the PPT activity likely occurs by a Michael addition of Pro-1 to C-4 of the inhibitor. Attempts to crystallize the inactivated complex to confirm the structure of the adduct on the covalently modified Pro-1 by X-ray crystallography were not successful. Nor was it possible to unambiguously interpret electron density observed in the active sites of the native crystals soaked with the inhibitor. This may be due to crystal packing in that the side chain of Glu-16 from an adjacent trimer occupies one active site. However, this crystal contact may be partially responsible for the high-resolution quality of these MIF crystals. Nonetheless, because MIF is a member of the tautomerase superfamily, a group of structurally homologous proteins that share a β-α-β structural motif and a catalytic Pro-1, 2-OPB may find general use as a probe of tautomerase superfamily members that function as PPTs.

Novel synthesis of 2-oxo-4-phenyl-3-butynoic acid, a new inhibitor and alternate substrate of pyruvate decarboxylase

An improved method is reported for the synthesis of 2-oxo acids and is applied to the synthesis of 2-oxo-4-phenyl-3-butynoic acid. The compound is synthesized by reacting the N-methoxy-N-methylamide of monoethyloxalic acid with lithium phenylacetylide yielding ethyl 2-oxo-4-phenyl-3-butynoate (78% yield), followed by strictly pH-controlled hydrolysis to the free acid in nearly quantitative yield. The compound is shown to be a potent irreversible inhibitor of brewers' yeast pyruvate decarboxylase, in addition to producing both cis- and trans-cinnamic acids as products of turnover. The formation of these isomeric cinnamic acids can be rationalized if the thiamin diphosphate-bound α-carbanion/enamine intermediate resulting from decarboxylation is protonated at the side chain γ carbon to form two diastereomeric allenols, whose tautomerization and hydrolysis lead to the two products.