2834-03-9

Usage

InChI:InChI=1/C16H28O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16(17)18/h2-13H2,1H3,(H,17,18)

Upstream product

• 765-13-9 pentadec-1-yne 
• 124-38-9 carbon dioxide 
• 152757-55-6 2-bromo-1-pentadecene 
• 138055-43-3 ethyl hexadec-2-ynoate 
• 124-25-4 myristylaldehyde 
• 112-72-1 1-Tetradecanol 
• 15890-72-9 laurylmagnesium bromide 
• 765-09-3 1-bromotridecane 
• 471-25-0 Propiolic acid 
• 917-64-6 methyl magnesium iodide 

Downstream Products

• 54794-69-3 (2E,4E)-N-isobutylhexadeca-2,4-dienamide 
• 59404-48-7 (2E,4E)-hexadecadienoic acid 
• 2825-68-5 cis-Hexadec-2-enoic acid 

Relevant academic research and scientific papers

2-Octadecynoic acid as a dual life stage inhibitor of Plasmodium infections and plasmodial FAS-II enzymes

The malaria parasite Plasmodium goes through two life stages in the human host, a non-symptomatic liver stage (LS) followed by a blood stage with all clinical manifestation of the disease. In this study, we investigated a series of 2-alkynoic fatty acids (2-AFAs) with chain lengths between 14 and 18 carbon atoms for dual in vitro activity against both life stages. 2-Octadecynoic acid (2-ODA) was identified as the best inhibitor of Plasmodium berghei parasites with ten times higher potency (IC50 = 0.34 μg/ml) than the control drug. In target determination studies, the same compound inhibited three Plasmodium falciparum FAS-II (PfFAS-II) elongation enzymes PfFabI, PfFabZ, and PfFabG with the lowest IC50 values (0.28-0.80 μg/ml, respectively). Molecular modeling studies provided insights into the molecular aspects underlying the inhibitory activity of this series of 2-AFAs and a likely explanation for the considerably different inhibition potentials. Blood stages of P. falciparum followed a similar trend where 2-ODA emerged as the most active compound, with 20 times less potency. The general toxicity and hepatotoxicity of 2-AFAs were evaluated by in vitro and in vivo methods in mammalian cell lines and zebrafish models, respectively. This study identifies 2-ODA as the most promising antiparasitic 2-AFA, particularly towards P. berghei parasites.

Chemical conjugation of 2-hexadecynoic acid to C5-curcumin enhances its antibacterial activity against multi-drug resistant bacteria

The first total synthesis of a C5-curcumin-2-hexadecynoic acid (C5-Curc-2-HDA, 6) conjugate was successfully performed. Through a three-step synthetic route, conjugate 6 was obtained in 13% overall yield and tested for antibacterial activity against methi

2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections

Acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of Plasmodium yoelii infections. Since the type II fatty acid biosynthesis pathway (PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the inhibitory potential of the HDAs against multiple P. falciparum FAS-II (PfFAS-II) elongation enzymes was also evaluated. The highest antiplasmodial activity against blood stages of P. falciparum was displayed by 5-HDA (IC50 value 6.6 μg/ml), whereas the 2-HDA was the only acid arresting the growth of liver stage P. yoelii infection, in both flow cytometric assay (IC50 value 2-HDA 15.3 μg/ml, control drug atovaquone 2.5 ng/ml) and immunofluorescence analysis (IC50 2-HDA 4.88 μg/ml, control drug atovaquone 0.37 ng/ml). 2-HDA showed the best inhibitory activity against the PfFAS-II enzymes PfFabI and PfFabZ with IC 50 values of 0.38 and 0.58 μg/ml (IC50 control drugs 14 and 30 ng/ml), respectively. Enzyme kinetics and molecular modeling studies revealed valuable insights into the binding mechanism of 2-HDA on the target enzymes. All HDAs showed in vitro activity against Trypanosoma brucei rhodesiense (IC50 values 3.7-31.7 μg/ml), Trypanosoma cruzi (only 2-HDA, IC50 20.2 μg/ml), and Leishmania donovani (IC50 values 4.1-13.4 μg/ml) with generally low or no significant toxicity on mammalian cells. This is the first study to indicate therapeutic potential of HDAs against various parasitic protozoa. It also points out that the malarial liver stage growth inhibitory effect of the 2-HDA may be promoted via PfFAS-II enzymes. The lack of cytotoxicity, lipophilic nature, and calculated pharmacokinetic properties suggests that 2-HDA could be a useful compound to study the interaction of fatty acids with these key P. falciparum enzymes.

2-Alkynoic fatty acids inhibit topoisomerase IB from Leishmania donovani

2-Alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. In this work we synthesized the 2-octadecynoic acid (2-ODA), 2-hexadecynoic acid (2-HDA), and 2-tetradecynoic acid (2-TDA) and show that 2-ODA is the best inhibitor of the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB) with an EC50 = 5.3 ± 0.7 μM. The potency of LdTopIB inhibition follows the trend 2-ODA > 2-HDA > 2-TDA, indicating that the effectiveness of inhibition depends on the fatty acid carbon chain length. All of the studied 2-alkynoic fatty acids were less potent inhibitors of the human topoisomerase IB enzyme (hTopIB) as compared to LdTopIB. 2-ODA also displayed in vitro activity against Leishmania donovani (IC50 = 11.0 μM), but it was less effective against other protozoa, Trypanosoma cruzi (IC50 = 48.1 μM) and Trypanosoma brucei rhodesiense (IC 50 = 64.5 μM). The antiprotozoal activity of the 2-alkynoic fatty acids, in general, followed the trend 2-ODA > 2-HDA > 2-TDA. The experimental information gathered so far indicates that 2-ODA is a promising antileishmanial compound.

Antibacterial activity of 2-alkynoic fatty acids against multidrug-resistant bacteria

The first study aimed at determining the structural characteristics needed to prepare antibacterial 2-alkynoic fatty acids (2-AFAs) was accomplished by synthesizing several 2-AFAs and other analogs in 18-76% overall yields. Among all the compounds tested, the 2-hexadecynoic acid (2-HDA) displayed the best overall antibacterial activity against Gram-positive Staphylococcus aureus (MIC = 15.6 μg/mL), Staphylococcus saprophyticus (MIC = 15.5 μg/mL), and Bacillus cereus (MIC = 31.3 μg/mL), as well as against the Gram-negative Klebsiella pneumoniae (7.8 μg/mL) and Pseudomonas aeruginosa (MIC = 125 μg/mL). In addition, 2-HDA displayed significant antibacterial activity against methicillin-resistant S. aureus (MRSA) ATCC 43300 (MIC = 15.6 μg/mL) and clinical isolates of MRSA (MIC = 3.9 μg/mL). No direct relationship was found between the antibacterial activity of 2-AFAs and their critical micelle concentration (CMC) suggesting that the antibacterial properties of these fatty acids are not mediated by micelle formation. It was demonstrated that the presence of a triple bond at C-2 and the carboxylic acid moiety in 2-AFAs are important for their antibacterial activity. 2-HDA has the potential to be further evaluated for use in antibacterial formulations.

Total Synthesis of the Proposed Structure of Mycobactin J

The total synthesis of the proposed structure of mycobactin J (MJ), a metabolite of Mycobacterium tuberculosis, is presented. The highlights of the synthesis include a careful control of the Z-stereochemistry of the unsaturated long chain fatty acid, a biomimetic construction of the oxazoline building block and the carriage of an unprotected phenol throughout the synthesis.

Structure and absolute configuration of mycobactin J

Mycobactin J 1 is a commercially available siderophore isolated from Mycobacterium avium subsp. paratuberculosis. There are discrepancies between previous reports of its structure and none have addressed its absolute configuration. We report here the complete structure and stereochemistry of mycobactin J, along with methodology to enable the determination of the absolute configuration of other mycobactins on a small scale.

Expedient synthesis of unsaturated amide alkaloids from Piper spp: Exploring the scope of recent methodology

The Sakai aryl aldehyde - cyclic ketone aldol - Grob fragmentation sequence was extended to cinnamaldehyde and cyclohexanone, and the product was elaborated to analogues of the alkaloid piperstachine. The effects of substituents on the reaction involving cinnamaldehyde were studied. The aldol-fragmentation sequence failed with benzaldehyde when cyclooctanone or cyclobutanone was substituted for cyclohexanone or cyclopentanone, and the reasons for this failure were examined. Four-carbon Wittig homologation of the piperonal-cyclobutanone aldol-fragmentation product, a hypothetical route to alkaloids such as retrofractamide A, was thus not viable. Instead, three-carbon homologation of the readily available piperonal-cyclopentanone product, using alkyne chemistry recently disclosed by Lu and Trost, afforded these alkaloids in excellent overall yield. The alkyne isomerization was also used to effect efficient syntheses of pellitorine and several other non-aromatic 2E,4E-dienoic Piper amide alkaloids. The Sakai aryl aldehyde - cyclic ketone aldol - Grob fragmentation sequence was extended to cinnamaldehyde and cyclohexanone, and the product was elaborated to analogues of the alkaloid piperstachine. The effects of substitutents on the reaction involving cinnamaldehyde were studied. The aldol-fragmentation sequence failed with benzaldehyde when cyclooctanone or cyclobutanone was substituted for cyclohexanone or cyclopentanone, and the reasons for this failure were examined. Four-carbon Wittig homologation of the piperonal-cyclobutanone aldol-fragmentation product, a hypothetical route to alkaloids such as retrofractamide A, was thus not viable. Instead, three-carbon homologation of the readily available piperonal-cyclopentanone product, using alkyne chemistry recently disclosed by Lu and Trost, afforded these alkaloids in excellent overall yield. The alkyne isomerization was also used to effect efficient syntheses of pellitorine and several other non-aromatic 2E,4E-dienoic Piper amide alkaloids.