Friday, 1 February 2019

Design, synthesis and antimicrobial activity of usnic acid derivatives

Graphical abstract: Design, synthesis and antimicrobial activity of usnic acid derivatives

Design, synthesis and antimicrobial activity of usnic acid derivatives


Usnic acid, a dibenzofuran, was originally isolated from lichens producing secondary metabolites, and is well known as an antibiotic, but is also endowed with several other interesting properties. Thus, the goal of this paper is the design of new usnic acid derivatives and evaluation of their antimicrobial activity. All newly synthesized compounds possess good antibacterial activity with MIC ranging from 1.02–50.93 × 10−2 mmol mL−1 and MBC from 2.05–70.57 × 10−2 mmol mL−1. The most sensitive bacterial species was Staphylococcus aureus, while Pseudomonas aeruginosa and Escherichia coli were the most resistant among the ATCC strains, and MRSA was the most resistant among all tested bacteria (ATCC and clinical isolates). Their antifungal activity was very strong (MIC = 0.35–7.53 × 10−2 mmol mL−1 and MFC = 0.70–15.05 × 10−2 mmol mL−1) – better than those of reference compounds and usnic acid itself. The most sensitive fungal species was Trichoderma viride, while Penicillium versicolor var. cyclopium appeared to be the most resistant. It should be mentioned that in general most of the compounds showed weaker antibacterial activity, but better antifungal properties than usnic acid itself. The results allow us to conclude that the title compounds are good lead compounds for novel more active antibacterial drugs. On the other hand, these compounds are very promising as antifungals.

Tuesday, 29 January 2019

Large scale synthesis of chiral (3Z,5Z)-2,7-dihydro-1H-azepine-derived Hamari ligand for general asymmetric synthesis of tailor-made amino acids.

str3 str4
(R)-2,2′-bis(bromomethyl)-1,1′-binaphthalene ((R)-17) was prepared in the identical manner and had identical analytical properties to those given here.
1H NMR (400 MHz, CDCl3): δ 4.25 (4H, s, 2 × CH2), 7.07 (2H, dd, J = 8.4, 0.8 Hz, ArH), 7.27 (2H, ddd, J = 8.4, 6.8, 1.2 Hz, ArH), 7.48 (2H, ddd, J = 8.2, 6.8, 1.2 Hz, ArH), 7.74 (2H, d, J = 8.6 Hz, ArH), 7.92 (2H, d, J = 8.2 Hz, ArH), 8.02 (2H, d, J = 8.6 Hz, ArH).
13C NMR (100.6 MHz, CDCl3): δ 32.6 (CH2), 126.80 (ArCH), 126.82 (ArCH), 126.84 (ArCH), 127.7 (ArCH), 128.0 (ArCH), 129.4 (ArCH), 132.5 (quaternary ArC), 133.3 (quaternary ArC), 134.1 (quaternary ArC), 134.2 (quaternary ArC).
[α]20D = +173.8° (c = 1.0, CHCl3).

Abstract Image
An advanced process for large scale (500 g) preparation of a (3Z,5Z)-2,7-dihydro-1H-azepine-derived chiral tridentate ligand (Hamari ligand), widely used for asymmetric synthesis of tailor-made α-amino acids via the corresponding glycine Schiff base Ni(II) complex, is disclosed. The process includes amidation, bis-alkylation, and precipitation/purification of the target compound by TFA as a counterion.
Large Scale Synthesis of Chiral (3Z,5Z)-2,7-Dihydro-1H-azepine-Derived Hamari Ligand for General Asymmetric Synthesis of Tailor-Made Amino Acids
 Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka 533-0024, Japan
 Hamari Chemicals USA, San Diego Research Center11494 Sorrento Valley Road, San Diego, California 92121, United States
§ Department of Organic Chemistry I, Faculty of ChemistryUniversity of the Basque Country UPV/EHUPaseo Manuel Lardizábal 3, 20018 San Sebastián, Spain
 IKERBASQUE, Basque Foundation for ScienceMaría Díaz de Haro 3, Plaza Bizkaia, 48013 Bilbao, Spain
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.8b00406
Publication Date (Web): January 18, 2019
Copyright © 2019 American Chemical Society
This article is part of the Japanese Society for Process Chemistry special issue.