Induced biosyntheses of a novel butyrophenone and two aromatic polyketides in the plant pathogen Stagonospora nodorum

Fungal aromatic compounds comprise an important and structurally diverse group of secondary metabolites.Several genome sequencing projects revealed many putative biosynthetic gene clusters of fungal aromatic compounds,but many of these genes seem to be silent under typical laboratory culture conditions.To gain access to this untapped reservoir of natural products,we utilized chemical epigenetic modifiers to induce the expression of dormant biosynthetic genes.As a result,the concomitant supplementation of the histone deacetylase inhibitors suberoylanilide hydroxamic acid(500mM)and nicotinamide(50mM)to the culture medium of a fungal pathogen,Stagonospora nodorum,resulted in the isolation of three aromatic compounds(1-3),including a novel natural butyrophenone,(+)-4'-methoxy-(2S)-methylbutyrophenone(1),and two known polyketides,alternariol(2)and(-)-(3R)-mellein methyl ether(3).

Improved Method for the Total Synthesis of Azaperone and Investigation of Its Electrochemical Behavior in Aqueous Solution

Azaperone,with anti-anxiety and anti-aggressive activities used in veterinary medicine,is a member of the butyrophenone class.It is ordinarily utilized for a wide range of indications,such as sedation,obstetrics,and anesthesia.In this research,an improved synthetic route is presented for azaperone using a phase-transfer catalyst(PTC).In general,it was synthesized as a dopamine antagonist in four steps.The bis(2-chloroethyl)amine intermediate is easily obtained after the conversion of the alcohol groups into the chloride leaving group using thionyl chloride(95%yields).The alkylation of commercially available 2-amino pyridine in the presence of PTC was then carried out,giving 1-(pyridin-2-yl)piperazine with 75%yield.1-(Pyridin-2-yl)piperazine was finally alkylated using 4-chloro-1-(4-fluorophenyl)butan-1-one to achieve azaperone with 60%yield.The butyrophenone intermediate was obtained via the Friedel-Crafts reaction of fluorobenzene with 4-chlorobutyryl chloride in the presence of AlCl3.High efficiency,gentle reaction conditions,and fast and simple procedure are the advantages of this method.Also,the electrochemical oxidation behaviour of azaperone was investigated using cyclic and differential pulse voltammetry techniques.Cyclic voltammetric studies indicated an irreversible process for azaperone electro-oxidation with a peak potential of 0.78 V in a phosphate buffer solution(pH=7.0)vs.Ag/AgCl(saturated KCl)electrode.The value of the peak current vs.the azaperone concentration was enhanced linearly in the range of 10―70μmol/L,and the detection limit was found to be 3.33μmol/L.