Synthesis and Antibacterial Activities of Yanglingmycin Analogues

Abstract

The synthesis of Yanglingmycin and its enantiomer, along with eighteen Yanglingmycin analogues is reported. The structures were confirmed mainly by analyses of NMR spectral data. Antibacterial activity assays showed that Yanglingmycin and some of its analogues exhibited significant antibacterial activities against two important agricultural pathogenic bacteria, Ralstonia solanacearum and Pseudomonas syringae pv. actinidiae, with minimum inhibitory concentration (MIC) values ranging from 3.91 to 15.62 µg/mL. The antibacterial activities exhibited by Yanglingmycin and its analogues are promising, suggesting potential in the development of compounds for novel bactericides.Key words Yanglingmycin; structural analogue; substituted cyclic azole; antibacterial activity Bacterial diseases pose a major threat to agricultural production worldwide. For example, Ralstonia solanacearum, which causes plant bacterial wilt, is one of the most destructive plant pathogens, and affects many regions of the world. 1)It is estimated that R. solanacearum is responsible for US$ 1 billion in losses each year.2) Pseudomonas syringae pv. actinidiae, which causes kiwifruit canker, is another devastating plant pathogen and has received significant attention in recent years.3-6) Thus, there has been considerable interest in development of bactericides for Ralstonia solanacearum and Pseudomonas syringae pv. actinidiae. Unfortunately, there have been few reports of effective bactericides against these pathogens. In the process of screening new agricultural antibiotics, we report the synthesis a new broad spectrum antibiotic, Yanglingmycin (Fig. 1), which was found to be effective against the previously mentioned pathogens. 7) Although Yanglingmycin can be isolated from the fermentation broth of Streptomyces djakartensis, the yield is too low to conduct experiments to determine the mechanism of bactericidal action. In order to investigate the bactericidal activities of Yanglingmycin and its analogues, Yanglingmycin and its analogues were designed and synthesized. In this paper, Yanglingmycin and its enantiomer and eighteen Yanglingmycin analogues were synthesized and their antibacterial activities against Ralstonia solanacearum and Pseudomonas syringae pv. actinidiae are reported. ResultsChemistry Chart 1 describes the synthesis of all target compounds. Benzonitrile, 2-hydroxybenzonitrile, and 4-hydroxybenzonitrile were used as starting material for the Pinner reaction to obtain the corresponding methyl benzimidate hydrochlorides, 8) which were then reacted with each the following compounds: L-serine methyl ester hydrochloride, D-serine methyl ester hydrochloride, L-cysteine methyl ester hydrochloride, D-cysteine methyl ester hydrochloride, L-2,3-diaminopropionic acid methyl ester hydrochloride, and D-2,3-diaminopropionic acid methyl ester hydrochloride.9,10) Amino acid methyl ester hydrochlorides were obtained by reacting the corresponding amino acids with AcCl in MeOH.11) The products were reduced by LiAlH 4 to obtain Yanglingmycin and its an...

Design and Synthesis of New 2-Aryl-4,5-Dihydro-thiazole Analogues: In Vitro Antibacterial Activities and Preliminary Mechanism of Action

“…The carboxylates 1e – 10e , 1e′ – 10e′ were reduced by NaBH 4 in EtOH to furnish the corresponding 2-aryl-4-hydroxymethyly-4,5-dihydrothiazoles 1h – 10h , 1h′ – 10h′ and treated with 10% sodium hydroxide solution in EtOH to get the corresponding 2-aryl-4,5-dihydrothiazole-4-carboxylic acids 1a – 10a , 1a′ – 10a′ . The structures of all the compounds were confirmed mainly by analyses of their NMR spectral and mass spectrometry data or reference to related literature [3,13,14,15].…”

“…The tested bacteria were incubated in the Mueller–Hinton broth for 12 h at 37 °C at 190 rpm, and the spore concentration was diluted to approximately 1 × 10 5 –1 × 10 6 CFU/mL with Mueller–Hinton broth. After incubation for 24 h at 37 °C, the MICs were examined by observing the first few holes transparent [3].…”

“…Unfortunately, there have been few reports of effective bactericides against these pathogens. In the process of screening new agricultural bactericides, we found that some 2-arylthiazolines such as ( S )-2-(2′-hydroxyphenyl)-4-hydroxymethyl-4,5-dihydrothiazole and ( R )-2-(2′-hydroxyphenyl)-4-hydroxymethyl-4,5-dihydrothiazole exhibited potent antibacterial activities [2,3,4,5]. Inspired by these results, we wondered whether the 2-arylthiazoline scaffold could be a lead compound for agricultural bactericides.…”

Cooperative Reinforcement of Ionic Liquid and Reactive Solvent on Enzymatic Synthesis of Caffeic Acid Phenethyl Ester as an In Vitro Inhibitor of Plant Pathogenic Bacteria

“…For natural extracts and compounds, the EC 50 and MIC values of coumarin were 198.64 µg/mL and 384 µg/mL [ 46 ], and the MIC values of some plant extracts ranged from 3.91 µg/mL–128 µg/mL, including leaf essential oil isolated from Macleaya cordata R. Br. [ 47 ], yanglingmycin and its analogues [ 48 ] and polyphenols isolated from Spiromastix sp. MCCC 3A00308 [ 49 ].…”

Efficient Synthesis and Antibacterial Evaluation of (±)-Yanglingmycin and Its Analogues

“…As reported by us recently, both (−)-Yanglingmycin and (+)-Yanglingmycin exhibited satisfying antibacterial activity for Pseudomonas syringae pv. Actinidiae and Ralstonia solanacearum with peak MIC values 7.81 and 15.62 μg·mL −1 , respectively [8] . As far as the antibacterial data of Yanglingmycin was concerned, we postulated that this compound has the potential to act as the lead compound for the development of new antibacterial drugs.…”