Absolute Stereochemistry of Antifungal Limonene-1,2-diols from Lippia rubella
- PDF / 350,756 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 74 Downloads / 212 Views
ORIGINAL PAPER
Absolute Stereochemistry of Antifungal Limonene-1,2-diols from Lippia rubella Suzana Guimarães Leitão 1 & Gabriel R. Martins 1 & Lucero Martínez-Fructuoso 2 & Danila de Sousa Silva 1 Thamirys Silva da Fonseca 1 & Caroline Vianna V. Castilho 1 & Leopoldo Clemente Baratto 1 & Daniela S. Alviano 3 & Celuta Sales Alviano 3 & Gilda Guimarães Leitão 4 & Rogelio Pereda-Miranda 2
&
Received: 26 May 2020 / Accepted: 15 July 2020 # Sociedade Brasileira de Farmacognosia 2020
Abstract From the active dichloromethane-soluble extract of Lippia rubella (Moldenke) T.R.S. Silva & Salimena, Verbenaceae (MIC = 78 μg/ml against Cryptococcus neoformans), two diastereomers of limonene-1,2-diol were isolated by countercurrent chromatography. An extensive NMR exploration to address the problem of distinguishing and evaluating the stereochemical influences of the C-2 hydroxy substituent on hydrogen and carbon chemical shifts of the natural products confirmed that these natural antifungal monoterpenes are derived from R-(+)-limonene. The absolute stereochemistry for both isolated diols was confirmed by the application of Mosher esters methodology. For the novel synclinal 1,2-diol, its structure was confirmed as (−)-(1S,2R,4R)1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol, which displayed a stronger antifungal activity against Crytococcus neoformans (MIC = 31.25 μg/ml; 184 μM) than the trans-diaxial 1,2-diol (2) which corresponded to the (+)-(1S,2S,4R) isomer (MIC = 250 μg/ml; 1470 μM) probably the most frequently distributed stereoisomer in volatile oils. The natural occurrence of 1 and 2 is being reported for the first time. Keywords Advanced Mosher’s method . Linear retention index . Monoterpene . Step gradient HSCCC . Optical isomer . Stereochemistry
Introduction The genus Lippia comprises circa 150 species occurring in the Americas and Africa (Almeida et al. 2018). In Brazil, there are 84 species, of which 60 are endemic (Salimena Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43450-020-00081-x) contains supplementary material, which is available to authorized users. * Suzana Guimarães Leitão [email protected] 1
Faculdade de Farmácia, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
2
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, 04510 Mexico City, DF, Mexico
3
Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
4
Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
and Múlgura et al. 2015). Lippia species are distinctly recognized by their aromas due to the high content of volatile oils (Pascual et al. 2001). Leaves or aerial parts are traditionally used to treat gastrointestinal and respiratory disorders, generally prepared as infusion or decoction which is orally administered (Pascual et al. 2001). Some species are applied externally
Data Loading...
