1. A chiron approach to the total synthesis of (-)-juglomycin A, (+)-kalafungin, (+)-frenolicin B, and (+)-deoxyfrenolicin
Rodney A Fernandes, Vijay P Chavan, Sandip V Mulay, Amarender Manchoju J Org Chem. 2012 Nov 16;77(22):10455-60. doi: 10.1021/jo3019939. Epub 2012 Oct 31.
A general, efficient, and common strategy for the synthesis of (-)-juglomycin A, (+)-kalafungin, (+)-frenolicin B, and (+)-deoxyfrenolicin is reported here. The strategy involves the synthesis of a key building block alkyne from a cheap chiral pool material, D-glucono-δ-lactone, Dötz benzannulation, oxa-Pictet-Spengler reaction, and H(2)SO(4)-mediated epimerization.
2. Synthetic and Biological Studies of Juglorubin and Related Naphthoquinones
Shogo Kamo, Tatsuo Saito, Yasuha Kusakabe, Shusuke Tomoshige, Masanobu Uchiyama, Kazunori Tsubaki, Kouji Kuramochi J Org Chem. 2019 Nov 1;84(21):13957-13966. doi: 10.1021/acs.joc.9b02119. Epub 2019 Oct 23.
Juglorubin, juglorescein, and juglocombins A/B are naturally occurring naphthoquinone dimers isolated from Streptomyces sp. These dimers are proposed to be biogenetically derived from juglomycin C, a monomeric naphthoquinone isolated from the same Streptomyces sp. In this study, the dimerization of a juglomycin C derivative, a key step in the total syntheses of these natural products, was investigated. Juglorubin was synthesized from the minor product of the dimerization via the formation of the juglocombin A/B stereoisomers. A mechanism for the dimerization reaction as well as a plausible biosynthetic pathway to obtain juglorubin from juglomycin C are proposed. Furthermore, the antibacterial and cytotoxic activities of five synthetic compounds were evaluated. Among the compounds tested in this study, 1'-O-methyljuglocombin B dimethyl ester and juglomycin C exhibited antibacterial activity against Bacillus subtilis. 1'-O-Methyljuglocombin B dimethyl ester and juglomycin C showed cytotoxicity against human colon carcinoma HCT116 cells and human leukemia HL-60 cells. 1'-O-Methyljuglocombin B dimethyl ester exhibited cytotoxicity against human normal MRC-5 cells as strong as that against human cancer cells. In contrast, juglomycin C was less toxic against normal MRC-5 cells, indicating a significant selectivity toward cancer cells.
3. Antibacterial potential of Juglomycin A isolated from Streptomyces achromogenes, an endophyte of Crocus sativus Linn
T Ahmad, P Arora, Y Nalli, A Ali, S Riyaz-Ul-Hassan J Appl Microbiol. 2020 May;128(5):1366-1377. doi: 10.1111/jam.14568. Epub 2020 Jan 16.
Aim: To evaluate the antimicrobial potential of Juglomycins isolated from Streptomyces achromogenes E91CS4, an endophyte of Crocus sativus Linn. Methods and results: The extract from E91CS4 displayed significant antimicrobial activity against several pathogens. The endophyte was identified as S. achromogenes on by 16S ribosomal gene analysis. Chemical investigation of the extract led to the isolation of two naphthoquinone antibiotics, Juglomycin A and B. Juglomycin A inhibited several pathogens, with an MIC value of 13·7µg ml-1 , whereas it was most potent against Escherichia coli, Bacillus thuringiensis and Xanthobacter flavus with MIC values of 6·8, 3·4 and 6·8 µg ml-1 respectively. It was found to reduce the biofilm formation in E. coli through inhibition of swimming and swarming motilities and downregulation of fimH gene. The α-haemolysin-related gene (hlyA) was also downregulated indicating that the compound is also reducing the virulence in E. coli. In vitro time kill kinetics showed efficient bactericidal activity of this compound. Furthermore, Juglomycin A inhibited bacterial transcription/translation in vitro, while also inducing postantibiotic effect in E. coli. Conclusions: Juglomycin A is a potential antimicrobial compound against several bacterial pathogens, particularly, E. coli. Significance and impact of the study: This study showed the promising potential of Juglomycin A as an antimicrobial agent. Efforts should be made to scale up the production of this compound and conduct further studies to explore its efficacy as an antibiotic, using in vivo models.