104633-19-4

Upstream product

• 108-59-8 malonic acid dimethyl ester 
• 1571-08-0 methyl 4-formylbenzoate 
• 21928-11-0 methyl 4-(dimethylcarbamoyl)benzoate 

Downstream Products

• 52148-89-7 methyl (E)-4-(3-methoxy-3-oxoprop-1-en-1-yl)benzoate 
• 1034147-67-5 2-(4-carbomethoxyphenylcyclopropane)-1,1-dicarboxylic acid dimethyl ester 

Relevant academic research and scientific papers

Amides as surrogates of aldehydes for C-C bond formation: amide-based direct Knoevenagel-type condensation reaction and related reactions

Aldehydes are perhaps the most versatile compounds that enable many C-C bond forming reactions, which are not amenable for other subclasses of carbonyl compounds. We report the first use of amides as surrogates of aldehydes for C-C bond formation, namely,

Indium(III)-catalyzed knoevenagel condensation of aldehydes and activated methylenes using acetic anhydride as a promoter

The combination of a catalytic amount of InCl3 and acetic anhydride remarkably promotes the Knoevenagel condensation of a variety of aldehydes and activated methylene compounds. This catalytic system accommodates aromatic aldehydes containing a variety of electron-donating and -withdrawing groups, heteroaromatic aldehydes, conjugate aldehydes, and aliphatic aldehydes. Central to successfully driving the condensation series is the formation of a geminal diacetate intermediate, which was generated in situ from an aldehyde and an acid anhydride with the assistance of an indium catalyst.

Selection, synthesis, and anti-inflammatory evaluation of the arylidene malonate derivatives as TLR4 signaling inhibitors

Inhibition of TLR4 signaling is an important therapeutic strategy for intervention in the etiology of several pro-inflammatory diseases. There has been intensive research in recent years aiming to explore this strategy, and identify small molecule inhibitors of the TLR4 pathway. However, the recent failure of a number of advanced drug candidates targeting TLR4 signaling (e.g., TAK242 and Eritoran) prompted us to continue the search for novel chemical scaffolds to inhibit this critical inflammatory response pathway. Here we report the identification of a group of new TLR4 signaling inhibitors through a cell-based screening. A series of arylidene malonate analogs were synthesized and assayed in murine macrophages for their inhibitory activity against LPS-induced nitric oxide (NO) production. The lead compound 1 (NCI126224) was found to suppress LPS-induced production of nuclear factor-kappaB (NF-κB), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and nitric oxide (NO) in the nanomolar-low micromolar range. Taken together, this study demonstrates that 1 is a promising potential therapeutic candidate for various inflammatory diseases.

Asymmetric michael addition of ketones to alkylidene malonates and allylidene malonates via enamine - Metal lewis acid bifunctional catalysis

Novel enamine-metal Lewis acid bifunctional catalysts were successfully applied to the asymmetric Michael addition of ketones to alkylidene malonates, offering excellent stereoselectivity (up to >99% ee and >99:1 dr). The asymmetric Michael addition of ketones to allylidene malonates was also achieved.

Synthesis of polysubstituted 1,3-cyclohexadicnes from β-branched α,β-alkenals and monoesters of ylidenemalonic acids

3-Methyl- and 3-phenyl-2-butenal react with monoesters of alkylidene-, alkenylidene-, and arylmethylenemalonic acids in the presence of piperidine as the catalyst to give esters of 4,6-disubstituted 1,3-cyclohexadienecarboxylic acids in 23-96 % yields. Under the same conditions cyclohexylideneacetic aldehyde reacts with the monoesters of prenylidene- and benzylidenemalonic acid to afford mixtures of 1,8a-trans- and 1,8a-cis-isomers of 1-substituted alkyl 1,5,6,7,8,8a-hexahydronaphthalene-2-carboxylates, the ratios and configurations of which were determined by means of 1H NMR spectroscopy. In some cases the formation of cyclic dienes is impeded by the competing process of decarboxylation of acidic ylidenemalonates. The derivatives of 4,6-diphenyl-1,3-cyclohexadienecarboxylic acid were shown to be convenient precursors for the preparation of meta-terphenyls.