Carbon Chain Extension Research Articles

Novel Bioproduction of 1,6-Hexamethylenediamine from l-Lysine Based on an Artificial One-Carbon Elongation Cycle.

1,6-hexamethylenediamine (HMD) is an important precursor for nylon-66 material synthesis, while research on the bioproduction of HMD has been relatively scarce in scientific literature. As concerns about climate change, environmental pollution, and the depletion of fossil fuel reserves continue to grow, the significance of producing fundamental chemicals from renewable sources is becoming increasingly prominent. In recent investigations, the bioproduction of HMD from adipic acid has been reported but with lingering challenges concerning costly raw materials and low yields. Here, we have undertaken the reconstruction of the HMD synthetic pathway within Escherichia coli, which was constituted with l-lysine α-oxidase (Raip), LeuABCD, α-ketoacid decarboxylase (KivD), and transaminases (Vfl), leveraging a carbon chain extension module and a metabolic pathway of transaminase-decarboxylase cascade catalysis within the strain WD20, which successfully produce 46.7 ± 2.0 mg/L HMD. To increase the cascade activity and create a higher tolerance to external environmental disturbance for l-lysine to convert into HMD, another two enzymes d-alanine aminotransferase (Dat) and alpha-ketoacid decarboxylase (KdcA) were introduced into WD21 to provide flux flexibility for α-ketoacid metabolization, which was named "Smart-net metabolic engineering" in our research, and high-efficiency synthesis of HMD utilizing l-lysine as the substrate has been successfully achieved. Finally, we established a + 1C bioconversion multienzyme cascade catalyzing up to 65% conversion of l-lysine to HMD. Notably, our fermentation process yielded an impressive 213.5 ± 8.7 mg/L, representing the highest reported yield to date for the bioproduction of HMD from l-lysine.

Total Synthesis of Alternatamides B and D

AbstractThe total synthesis of alternatamines B and D is outlined. Alternatamine B demonstrates moderate antibacterial activity across a broad spectrum of bacteria. Both alternatamines B and D feature an intriguing 5,6‐dibromoindole skeleton, derived from a four‐step sequence starting with 3,4‐dibromoaniline and achieving a total yield of 48 %. The key steps involve: (a) functional group modifications, including iodination, of 3,4‐dibromoaniline with two bromine substituents to obtain the Sonogashira precursor; (b) indole synthesis through Sonogashira coupling and 5‐endo‐dig cyclization; (c) carbon chain extension and introduction of the nitrogen atom at the C3 of the indole. Subsequently, the tryptamine analogue was coupled with an L‐leucine derivative through amide bond formation after deprotection, yielding alternatamide D. The first total synthesis of alternatamine B was also achieved by selectively introducing a bromine substituent at the C2 of the indole, employing optimal bromination conditions.

Genetic and Morpho-Physiological Differences among Transgenic and No-Transgenic Cotton Cultivars.

Three carbon-chain extension genes associated with fatty acid synthesis in upland cotton (Gossypium hirsutum), namely GhKAR, GhHAD, and GhENR, play important roles in oil accumulation in cotton seeds. In the present study, these three genes were cloned and characterized. The expression patterns of GhKAR, GhHAD, and GhENR in the high seed oil content cultivars 10H1014 and 10H1041 differed somewhat compared with those of 10H1007 and 2074B with low seed oil content at different stages of seed development. GhKAR showed all three cultivars showed higher transcript levels than that of 2074B at 10-, 40-, and 45-days post anthesis (DPA). The expression pattern of GhHAD showed a lower transcript level than that of 2074B at both 10 and 30 DPA but a higher transcript level than that of 2074B at 40 DPA. GhENR showed a lower transcript level than that of 2074B at both 15 and 30 DPA. The highest transcript levels of GhKAR and GhENR were detected at 15 DPA in 10H1007, 10H1014, and 10H1041 compared with 2074B. From 5 to 45 DPA cotton seed, the oil content accumulated continuously in the developing seed. Oil accumulation reached a peak between 40 DPA and 45 DPA and slightly decreased in mature seed. In addition, GhKAR and GhENR showed different expression patterns in fiber and ovule development processes, in which they showed high expression levels at 20 DPA during the fiber elongation stage, but their expression level peaked at 15 DPA during ovule development processes. These two genes showed the lowest expression levels at the late seed maturation stage, while GhHAD showed a peak of 10 DPA in fiber development. Compared to 2074B, the oil contents of GhKAR and GhENR overexpression lines increased 1.05~1.08 folds. These results indicated that GhHAD, GhENR, and GhKAR were involved in both seed oil synthesis and fiber elongation with dual biological functions in cotton.

Total Synthesis of (-)-Batrachotoxin Enabled by a Pd/Ag-Promoted Suzuki-Miyaura Coupling Reaction.

Batrachotoxin is an extremely potent cardio- and neurotoxic steroidal alkaloid found in certain species of frogs, birds, and beetles. The steroidal 6/6/6/5-membered carbocycle (ABCD-ring) is U-shaped and functionalized with two double bonds, a six-membered C3-hemiacetal across the AB-ring, a seven-membered oxazepane on the CD-ring, and a dimethylpyrrolecarboxy group at the D-ring carbon chain. These structural features present an unusual and formidable synthetic challenge. Herein we report a total synthesis of batrachotoxin based on a newly devised convergent strategy through a 22-step sequence. Enantiopure AB-ring and D-ring fragments were prepared and subjected to a crucial C(sp2 )-C(sp2 ) coupling reaction. Although both C(sp2 ) centers were sterically encumbered by proximal tetrasubstituted carbon atoms, Ag2 O strongly promoted the Pd(PPh3 )4 -catalyzed Suzuki-Miyaura coupling reaction at room temperature, thereby connecting the two fragments without damaging their preexisting functionalities. Subsequent treatment with t-BuOK induced Dieckmann condensation to cyclize the C-ring. The judiciously optimized functionalizations realized oxazepane formation, carbon chain extension, and pyrrole carboxylic acid condensation to deliver batrachotoxin.

Total Synthesis of (−)‐Batrachotoxin Enabled by a Pd/Ag‐Promoted Suzuki–Miyaura Coupling Reaction

AbstractBatrachotoxin is an extremely potent cardio‐ and neurotoxic steroidal alkaloid found in certain species of frogs, birds, and beetles. The steroidal 6/6/6/5‐membered carbocycle (ABCD‐ring) is U‐shaped and functionalized with two double bonds, a six‐membered C3‐hemiacetal across the AB‐ring, a seven‐membered oxazepane on the CD‐ring, and a dimethylpyrrolecarboxy group at the D‐ring carbon chain. These structural features present an unusual and formidable synthetic challenge. Herein we report a total synthesis of batrachotoxin based on a newly devised convergent strategy through a 22‐step sequence. Enantiopure AB‐ring and D‐ring fragments were prepared and subjected to a crucial C(sp2)−C(sp2) coupling reaction. Although both C(sp2) centers were sterically encumbered by proximal tetrasubstituted carbon atoms, Ag2O strongly promoted the Pd(PPh3)4‐catalyzed Suzuki–Miyaura coupling reaction at room temperature, thereby connecting the two fragments without damaging their preexisting functionalities. Subsequent treatment with t‐BuOK induced Dieckmann condensation to cyclize the C‐ring. The judiciously optimized functionalizations realized oxazepane formation, carbon chain extension, and pyrrole carboxylic acid condensation to deliver batrachotoxin.

Biomass-Derived 2,3-Butanediol and Its Application in Biofuels Production

2,3-butanediol (2,3-BDO) is an important biomass-derived platform chemical with various applications. Currently, the biological conversion of renewable carbon sources with bacteria or yeasts is a sustainable way to produce 2,3-BDO. Various carbon sources including glucose, glycerol, molasses and lignocellulose hydrolysate have been used for 2,3-BDO production, and the 2,3-BDO concentration in the fermentation broth can be higher than 150 g/L by optimizing the operating parameters with fed-batch operations. Various derivatives can be produced from 2,3-BDO, including isobutyraldehyde, 1,3-butadiene, methyl ethyl ketone (MEK), diacetyl, etc.; among these, there is a large market demand for MEK and 1,3-butadiene each year. Some of the derivatives can be used as fuel additives or to produce biofuels. Generally, there are three ways to produce hydrocarbon fuels from 2,3-BDO, which are via the steps of dehydration, carbon chain extension, and hydrogenation (or hydrodeoxygenation), with MEK or 1,3-butadiene as the intermediates. C8–C16 alkanes can be produced by these routes, which can be potentially used as bio-jet fuels. This review article focuses on the microbial production of 2,3-BDO, the biomass feedstock used for fermentation, the recovery of 2,3-BDO from the fermentation broth as well as the downstream derivative products and their potential application in bio-jet fuel production. It was concluded that 2,3-BDO is a promising biomass-derived product, but its production and application in the biofuel field is still facing the problem of high production cost. Future work is recommended to develop more efficient processes to increase the 2,3-BDO yield and more advanced technologies to produce hydrocarbon fuels.

Characterization of Oil Body and Starch Granule Dynamics in Developing Seeds of Brassica napus.

Brassica napus is the most important oilseed crop in the world, and the lipid was stored in the oil body (OB) in the form of triacylglycerol. At present, most of studies on the relationship between oil body morphology and seed oil content in B. napus was focused on mature seeds. In the present study, the OBs in different developing seeds of B. napus with relatively high oil content (HOC) of about 50% and low oil content (LOC) of about 39% were analyzed. It was revealed that the size of OBs was first increased and then decreased in both materials. And in late seed developmental stages, the average OB size of rapeseed with HOC was higher than that of LOC, while it was reversed in the early seed developmental stages. No significant difference was observed on starch granule (SG) size in HOC and LOC rapeseed. Further results indicated that the expression of genes that involved in malonyl-CoA metabolism, fatty acid carbon chain extension, lipid metabolism, and starch synthesis in the rapeseed with HOC was higher than that of rapeseed with LOC. These results give some new insight for understanding the dynamics of OBs and SGs in embryos of B. napus.

One-Pot Carbon-Chain Extension for Nervonic/Carboxylic Acid Synthesis with the Assistance of Microwaves and Lithium Chloride

AbstractA mild, green, and convenient synthesis of nervonic acid was developed through a one-pot carbon-chain extension with the assistance of microwaves and lithium chloride (55% total yield); this is preferable to a previous six-step method (10% total yield). Compared with the previous lengthy refluxing process (>80 hours) with corrosive reagents, which furnished a mixture of cis- and trans-isomers, this efficient microwave protocol was more than a hundred times faster and was free of configurational isomerization. Notably, LiCl played a dual role in a Krapcho decarboxylation and subsequent ester hydrolysis under neutral conditions that replace the corrosive saponification in the previously reported one-pot method. Finally, this mild and efficient protocol was successfully applied to various carboxylic acids, including natural products, verifying its wide utility, easy operations, and attractive properties in organic synthesis.

Boosting the C–C Coupling of Bioethanol to Higher Alcohols by Inhibiting Aqueous Phase Reforming Reaction

A suitable catalyst with an exact match of the acidity/basicity, ingenious geometric structure, and proper electronic environment is vital to the Guerbet reaction for the synthesis of C6+ higher alcohols. Herein, we synthesized a series of Ni/MgAlO and NiSn/MgAlO catalysts based on hydrotalcite laminate for one-pot upgrading of aqueous bioethanol to C6+ higher alcohols. Through the introduction of Sn to form NiSn alloys, the Ni–Ni interactions were attenuated and the cleavage of C–C bonds was suppressed with a yield of 21.9% of C6+ higher alcohols at 250 °C. Meanwhile, by precisely adjusting the ratio of the metal cation Mg2+ to Al3+, the acidity and basicity of the catalysts were optimized and Ni/(4-Mg)AlO with an optimal ratio of 4 presented a considerable C6+ alcohol yield (25.2%) at even 220 °C, as well as an impressive ethanol conversion of 67.7%. Such an excellent activity achieved at lower temperature was attributed to highly dispersed Ni metal with a Ni(Mg)O solid solution structure, leading to the enormously inhibited aqueous ethanol reforming process and significant increased yield of higher alcohols. The results reveal that the electronic structure and coordination environment of metal sites as well as higher moderately basic and strong acid sites were demonstrated to be beneficial for carbon-chain extension of higher alcohols and ethanol selectivity for dehydrogenation/hydrogenation. Moreover, the number of metal, acid, and base sites should be balanced to inhibit side reactions.

Synthesis of estrone selenocyanate Compounds, anti-tumor activity evaluation and Structure-activity relationship analysis

Introducing different functional groups into steroid can bring unexpected changes in biological activity of the steroid. Using estrone as a raw material, through the functional group conversion and modification of the 17-carbonyl, the structural fragments with selenocyano groups were instilled in the form of amide, ester, and oxime ester, respectively, and various 17-substituted estrone selenocyanate derivatives were synthesized. In addition, different 3-substituted estrone selenocyanate derivatives were synthesized by introducing different selenocyanoalkoxy fragments into the 3-position of estrone in the form of alkyl ether. Furthermore, the selenocyano-containing moieties were embedded into the 2-position of estrone by means of amide, affording diverse 2-selenocyanoamide-estrone derivatives. The antiproliferative activities of the target compounds were screened by selecting tumor cell lines related to the expression of human hormones. The results showed that the introduction of selenocyano group into estrone could endow estrone with significant biological activity of inhibiting the proliferation of tumor cells. Structure-activity relationship research showed that the cytotoxicity of 3-selenocyanoalkoxy-estrone was further increased with the extension of alkyl carbon-chain within 8 carbon chain lengths. In addition, the cytotoxicity of the products with selenocyano via the form of amide was stronger than that of ester or ether. Selenocyano moiety instilled at the 2-position of estrone in the form of amide was more cytotoxic than that of 17- or 3-position. Among them, compound 21a has better inhibitory activity on tested tumor cells than positive controls Abiraterone and 2-methoxyestradiol. Research showed that the compound 21c induced programmed apoptosis in Sk-Ov-3 cancer cells, and compound 17d inhibited significantly the growth of human cervical cancer zebrafish xenografts in vivo, offering useful insights into the synthesis of steroid antitumor drugs.

Molecular dynamics simulation of wax molecules aggregational crystallization behavior during cooling of crude oil mixture

The crystallization behavior of wax molecules is the root cause of wax deposition. In this study, molecular dynamics simulations were used to investigate the aggregational crystallization behavior of wax molecules in a crude oil system. The results show that wax molecules produce ordered wax crystal structures from the disordered liquid phase crude oil system under van der Waals forces at low temperatures. The crystallization of wax molecules consists of three main processes: carbon chain extension, nucleation of wax molecules and wax crystal growth. The lower the temperature of the crude oil system and the lower the cooling rate, the higher the degree of aggregation of wax molecules, the smaller the number of wax crystals and the larger the crystal size. In addition, asphaltene molecules are found to aggregate by face-to-face stacking and T-shaped stacking at low temperatures. Based on the spatial steric hindrance effect, the asphaltene aggregates prevent further aggregation between wax crystal clusters. Asphaltenes lead to an increase in the liquid content of the wax deposit layer, causing the yield stress of the deposit to decrease and the structural strength to weaken.

Polyketides and terpenes in marine microalgae: Ecological roles and mechanisms of biosynthesis

Marine microalgae comprise a large number of polyketides and terpenes identified to date with highly diverse molecular scaffolds and the biological activities (Kalaitzis et al., 2010). These compounds play significant roles in marine food web and nutraceutical supplementation in marine animals. Compounds of this class are often synthesized by gene clusters with dedicated domains responsible for carbon chain extension and modification. The unique molecular structure of these compounds encourages people to investigate their biosynthetic mechanisms in-depth. In this review, we summarize relevant articles to unravel the shared mechanisms of these compounds to further understand the variety of domain organizations and the subsequent impact on the carbon chain diversity. In addition, the ecological role of these compounds and their modes of distribution in natural sea water is also discussed. We expect this study to bring multifaceted aspects regarding the assemblage and the ecological function of these secondary metabolites and to provide information to those who wish to obtain further understanding in these compounds whose structure and ecological function remain underexplored.

The fluorescence mechanism of carbon dots based on the separation and identification of small molecular fluorophores.

Carbon dots (CDs) have attracted much attention in theoretical researches and their practical applications due to their excellent optical properties, and many researchers discovered that flurophores play a very important role in synthesis process of CDs and the luminescence of prepared CDs. In this study, two CDs were pyrolysis with citric acid, N-acetyl-l-cysteine and glutathione derivatives as carbon sources. Four intermediate small molecules were separated from the prepared CDs through ultrafiltration and chromatography, and their chemical structures were determined. The formation process of CDs was monitored through identified small molecule intermediates and HPLC. It is speculated that the two CDs have the same formation pathway, including TPA (5-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyridine-3,7-dicarboxylic acid) synthesis, fluorophore polymerization, carbon chain extension, and carbonization. It was also discovered that these two CDs have the same fluorescence properties, thiazolopyridone structure, and nitrogen–sulfur co-doped functional groups are important reasons for the mixed excitation dependence of CDs. This study would provide valuable theoretical basis for the studies on preparation of excellent CDs, raw material selection, and CDs formation mechanism.

Sustainable and eco-friendly strategies for polyester-cotton blends dyeing in supercritical CO2

Traditional water medium dyeing of polyester-cotton fabrics consumes more water and energy, and causes serious environmental pollution in comparison with one-bath dyeing of single component fiber. To achieve sustainable dyeing of polyester-cotton blends, three reactive disperse dyes with s-triazine reactive group were synthesized, and supercritical CO2 was used as solvent to conduct the waterless dyeing. The results showed that one-bath dyeing of polyester-cotton blends could be successfully realized with the synthesized dyes. Dyeing performance of the synthesized dyes was constantly improved with the extension of carbon chain on aniline. Compared with other two dyes, the optimal color strength of polyester-cotton blends was obtained with dye 3 using dimethylsulfoxide as co-solvent, and K/S values up to 6.4 were obtained at 100 °C, 20 MPa and 120 min with a dimethylsulfoxide concentration of 80 %. σK/S values below 0.14 and washing and rubbing fastness above 4 were displayed for the colored samples. In addition, dyeing mechanism of polyester-cotton fabrics with the synthesized dyes was discussed combined with FT-IR measurement and stripping experiments.

Borata‐Alkene Species as Nucleophilic Reservoir

Abstractα‐Monoboryl anions show remarkable stability due to the valence deficiency of the adjacent three‐coordinate boron center and can be expressed as its resonance form, the borata‐alkene systems [R2B=CH2]−. The diversity of synthetic approaches as well as the properties of the C=B bond are disclosed in this review, dealing with both electronic and structural properties of the boryl moieties involved. Full characterization in solid state by X‐ray diffraction demonstrated the short distances between B and C, as a consequence of the boron ylide character in the boron‐stabilized carbanions. This review includes a collection of C−B length distances as well as 11B NMR data that can be useful for diagnostic evidence of the partial boron‐carbon double‐bond character. Natural bond orbital (NBO) analysis on DFT computed structures also supports and justifies the borata‐alkene character.The reactivity of the C=B bond acting as nucleophilic synthon is unveiled through extensive electrophilic trapping examples. The homologation protocols with diborylmethane, via single carbon chain extension, involves a facile introduction of the C(sp3)−B bonds, which can be subsequently transformed into functionalized target products, containing C−O, C−N or C−C bonds.magnified image

Probing the Hydrogen Bonding in Microsolvated Clusters of Au1,2-(Solv)n (Solv = C2H5OH, n-C3H7OH; n = 1-3 for Au-; n =1 for Au2-).

The microsolvation of gold anions in different alcohol solvents is demonstrated by the combination of anion photoelectron spectroscopy and quantum chemical calculations on the Au1,2-(Solv)n (Solv = C2H5OH, n-C3H7OH; n = 1-3 for Au-; n = 1 for Au2-). The microsolvation structures of these clusters and their corresponding neutrals are assigned by comparing calculations with experiments. In terms of overall regularity, the increasing solvation number (n) and carbon chain extension both can increase the stability of the anion. When n ≥ 2, these clusters have low-energy isomers, where conventional hydrogen bonds (HBs) compete with nonconventional HBs (NHBs). NHBs are dominant when n ≤ 2 and when n is increased, vice versa. Interestingly, a variety of theoretical calculations show that after the hydroxy H atom of the ethanol molecule forms a weak ionic HB with Au-, there are two lowest conformations of ethanol, trans and gauche, which could be coexisting in the molecular beams. Some theoretical methods also suggest that the gauche isomer is more stable than the trans one, which indicates that Au- may exist as a gold gauche effect similar to fluorine.

Silica‐immobilized acid ionic liquid: An efficient catalyst for pentanal self‐condensation

AbstractBACKGROUNDPentanal self‐condensation to 2‐propyl‐2‐heptenal is an important process of carbon chain extension for the industrial manufacture of 2‐propylheptanol, which is an important plasticizer alcohol. The existing industrial processes all use liquid alkali catalysts, so they suffer from problems such as difficult recovery and high costs for treatment of alkali‐containing wastewater. In the present work, three immobilized acid ionic liquids were prepared separately with SiO2, MCM‐41, and SBA‐15 as support for pentanal self‐condensation.RESULTSThe structures of the as‐prepared immobilized acid ionic liquids were confirmed with the help of FT‐IR, TG, SEM‐EDS, and N2 adsorption–desorption techniques. The characterization and activity evaluation results indicate that there are positive correlations among the number of hydroxyl groups on the support surface, ionic liquid loading, and the catalytic activity. Among the three immobilized acid ionic liquids, silica‐immobilized acid ionic liquids (SiO2‐IL‐SO3H) showed an extraordinary catalytic performance for pentanal self‐condensation because of its higher ionic liquid loading. The yield and selectivity of 2‐propyl‐2‐heptenal could respectively reach 73.9% and 91.5% under suitable reaction conditions and a high turnover number (TON) of 179.1 was obtained.CONCLUSIONPyridine adsorption infrared spectroscopy and density functional theory (DFT) simulation were employed to investigate the structure and acidity of SiO2‐IL‐SO3H. The optimized structures were obtained, and the calculation results indicate that the acidity of SiO2‐IL‐SO3H is higher than the corresponding homogeneous ionic liquid system, which may be the main reason for its excellent catalytic performance and catalytic efficiency. © 2020 Society of Chemical Industry

The effect of amine on the tribological properties and hydrolytic stability of borate ester additives

The effect of amine on the tribological properties and hydrolytic stability of borate ester additives was examined by adding different kinds and quantities of amines into borate esters, which formed boron–nitrogen (BN) coordination complex or BN ammonium complex. The results showed that all BN complexes obviously improved the hydrolytic stability of borate ester, and most of them promoted load-carrying abilities, friction-reducing and anti-wear properties. By comparison, BN extra-coordination complexes presented a little stronger hydrolytic stability and tribological properties than BN ammonium complexes. Generally, the hydrolytic stability and tribological properties of BN complexes is promoted with the extension of carbon chain of the added amine. The worn surface analyses revealed B2O3 deposits and adsorbed B- and N-containing organic compounds were responsible for the resulted tribological properties. Our results would provide some guidance to practical application of borate ester additives in lubricants.

Synergistic catalysis of acid–base bifunctional ionic liquids for pentanal self‐condensation reaction

AbstractBACKGROUNDPentanal self‐condensation to 2‐propyl‐2‐heptenal is an important process of carbon chain extension for industrial manufacture of 2‐propylheptanol. This reaction in industry employs an aqueous caustic alkali catalyst, causing several problems of equipment corrosion, treatment of alkali wastewater, etc. Herein, several acid–base bifunctional ionic liquids were synthesized for catalyzing pentanal self‐condensation.RESULTS[PEmim]Cl‐0.5Zn(CH3COO)2 exhibited a better catalytic performance, and the yield and selectively of 2‐propyl‐2‐heptenal could reach 82.0% and 86.6%, respectively. The recovered [PEmim]Cl‐0.5Zn(CH3COO)2 could be reused three times after being regenerated without a significant loss in its catalytic performance. The structures and charge properties of [PEmim]Cl‐Zn(CH3COO)2 and a complex of [PEmim]Cl‐Zn(CH3COO)2 and pentanal were simulated by density functional theory calculation. The results show that the action of acid and base sites of [PEmim]Cl‐Zn(CH3COO)2 can effectively activate pentanal by enhancing the electrophilicity or nucleophilicity of different pentanal molecules.CONCLUSIONThe acid–base synergetic effect of [PEmim]Cl‐Zn(CH3COO)2 could account for its high catalytic performance. An acid–base synergetic catalysis mechanism of [PEmim]Cl‐Zn(CH3COO)2 in pentanal self‐condensation was established. © 2019 Society of Chemical Industry

Structure-activity relationship study and biological evaluation of SAC-Garlic acid conjugates as novel anti-inflammatory agents

A series of S-allyl-l-cysteine (SAC) with garlic acid conjugates as anti-inflammatory agents were designed and synthesized. Among the 40 tested compounds, SMU-8c exhibited the most potent inhibitory activity to Pam3CSK4-induced nitric oxide (NO) in RAW264.7 macrophages with IC50 of 22.54 ± 2.60 μM. The structure-activity relationship (SAR) study suggested that the esterified carboxyl group, carbon chain extension and methoxylation phenol hydroxy could improve the anti-inflammatory efficacy. Preliminary anti-inflammatory mechanism studies showed that SMU-8c significantly down-regulated the levels of Pam3CSK4 triggered TNF-α cytokine in human THP-1 cells, mouse RAW 264.7 macrophages, as well as in ex-vivo human peripheral blood mononuclear cells (PBMC) with no influence on cell viability. SMU-8c specifically blocked the Pam3CSK4 ignited secreted embryonic alkaline phosphatase (SEAP) signaling with no influence to Poly I:C or LPS triggered TLR3 or TLR4 signaling. Moreover, SMU-8c suppressed TLR2 in HEK-Blue hTLR2 cells and inhibited the formation of TLR1-TLR2, and TLR2-TLR6 complex in human PBMC. In summary, SMU-8c inhibited the TLR2 signaling pathway to down-regulate the inflammation cytokines, such as NO, SEAP and TNF-α, to realize its anti-inflammatory activity.