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First Total Syntheses and Antimicrobial Evaluation of Penicimonoterpene, a Marine-Derived Monoterpenoid, and Its Various Derivatives

The first total synthesis of marine-derived penicimonoterpene (±)-1 has been achieved in four steps from 6-methylhept-5-en-2-one using a Reformatsky reaction as the key step to construct the basic carbon skeleton. A total of 24 new derivatives of 1 have also been designed and synthesized. Their stru...

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Autores principales: Zhao, Jian-Chun, Li, Xiao-Ming, Gloer, James B., Wang, Bin-Gui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071580/
https://www.ncbi.nlm.nih.gov/pubmed/24897384
http://dx.doi.org/10.3390/md12063352
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author Zhao, Jian-Chun
Li, Xiao-Ming
Gloer, James B.
Wang, Bin-Gui
author_facet Zhao, Jian-Chun
Li, Xiao-Ming
Gloer, James B.
Wang, Bin-Gui
author_sort Zhao, Jian-Chun
collection PubMed
description The first total synthesis of marine-derived penicimonoterpene (±)-1 has been achieved in four steps from 6-methylhept-5-en-2-one using a Reformatsky reaction as the key step to construct the basic carbon skeleton. A total of 24 new derivatives of 1 have also been designed and synthesized. Their structures were characterized by analysis of their (1)H NMR, (13)C NMR and HRESIMS data. Some of them showed significant antibacterial activity against Aeromonas hydrophila, Escherichia coli, Micrococcus luteus, Staphylococcus aureus, Vibrio anguillarum, V. harveyi and/or V. parahaemolyticus, and some showed activity against plant-pathogenic fungi (Alternaria brassicae, Colletotrichum gloeosporioides and/or Fusarium graminearum). Some of the derivatives exhibited antimicrobial MIC values ranging from 0.25 to 4 μg/mL, which were stronger than those of the positive control. Notably, Compounds 3b and 10 showed extremely high selectively against plant-pathogenic fungus F. graminearum (MIC 0.25 μg/mL) and pathogenic bacteria E. coli (MIC 1 μg/mL), implying their potential as antimicrobial agents. SAR analysis of 1 and its derivatives indicated that modification of the carbon-carbon double bond at C-6/7, of groups on the allylic methylene unit and of the carbonyl group at C-1, effectively enhanced the antimicrobial activity.
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spelling pubmed-40715802014-06-26 First Total Syntheses and Antimicrobial Evaluation of Penicimonoterpene, a Marine-Derived Monoterpenoid, and Its Various Derivatives Zhao, Jian-Chun Li, Xiao-Ming Gloer, James B. Wang, Bin-Gui Mar Drugs Article The first total synthesis of marine-derived penicimonoterpene (±)-1 has been achieved in four steps from 6-methylhept-5-en-2-one using a Reformatsky reaction as the key step to construct the basic carbon skeleton. A total of 24 new derivatives of 1 have also been designed and synthesized. Their structures were characterized by analysis of their (1)H NMR, (13)C NMR and HRESIMS data. Some of them showed significant antibacterial activity against Aeromonas hydrophila, Escherichia coli, Micrococcus luteus, Staphylococcus aureus, Vibrio anguillarum, V. harveyi and/or V. parahaemolyticus, and some showed activity against plant-pathogenic fungi (Alternaria brassicae, Colletotrichum gloeosporioides and/or Fusarium graminearum). Some of the derivatives exhibited antimicrobial MIC values ranging from 0.25 to 4 μg/mL, which were stronger than those of the positive control. Notably, Compounds 3b and 10 showed extremely high selectively against plant-pathogenic fungus F. graminearum (MIC 0.25 μg/mL) and pathogenic bacteria E. coli (MIC 1 μg/mL), implying their potential as antimicrobial agents. SAR analysis of 1 and its derivatives indicated that modification of the carbon-carbon double bond at C-6/7, of groups on the allylic methylene unit and of the carbonyl group at C-1, effectively enhanced the antimicrobial activity. MDPI 2014-06-03 /pmc/articles/PMC4071580/ /pubmed/24897384 http://dx.doi.org/10.3390/md12063352 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zhao, Jian-Chun
Li, Xiao-Ming
Gloer, James B.
Wang, Bin-Gui
First Total Syntheses and Antimicrobial Evaluation of Penicimonoterpene, a Marine-Derived Monoterpenoid, and Its Various Derivatives
title First Total Syntheses and Antimicrobial Evaluation of Penicimonoterpene, a Marine-Derived Monoterpenoid, and Its Various Derivatives
title_full First Total Syntheses and Antimicrobial Evaluation of Penicimonoterpene, a Marine-Derived Monoterpenoid, and Its Various Derivatives
title_fullStr First Total Syntheses and Antimicrobial Evaluation of Penicimonoterpene, a Marine-Derived Monoterpenoid, and Its Various Derivatives
title_full_unstemmed First Total Syntheses and Antimicrobial Evaluation of Penicimonoterpene, a Marine-Derived Monoterpenoid, and Its Various Derivatives
title_short First Total Syntheses and Antimicrobial Evaluation of Penicimonoterpene, a Marine-Derived Monoterpenoid, and Its Various Derivatives
title_sort first total syntheses and antimicrobial evaluation of penicimonoterpene, a marine-derived monoterpenoid, and its various derivatives
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071580/
https://www.ncbi.nlm.nih.gov/pubmed/24897384
http://dx.doi.org/10.3390/md12063352
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