Enantioselective syntheses of both enantiomers of 9'-dehydroxyimperanene and 7,8-dihydro-9'-dehydroxyimperanene and the comparison of biological activity between 9-norlignans and dihydroguaiaretic acids

Satoshi Yamauchi; Ryosuke Tanimura; Hisashi Nishiwaki; Kosuke Nishi; Takuya Sugahara; Masafumi Maruyama; Yoshitaka Ano; Koichi Akiyama; Taro Kishida

doi:10.1016/j.bmcl.2016.05.020

Enantioselective syntheses of both enantiomers of 9'-dehydroxyimperanene and 7,8-dihydro-9'-dehydroxyimperanene and the comparison of biological activity between 9-norlignans and dihydroguaiaretic acids

Bioorg Med Chem Lett. 2016 Jul 1;26(13):3019-3023. doi: 10.1016/j.bmcl.2016.05.020. Epub 2016 May 7.

Authors

Satoshi Yamauchi¹, Ryosuke Tanimura², Hisashi Nishiwaki², Kosuke Nishi², Takuya Sugahara³, Masafumi Maruyama², Yoshitaka Ano², Koichi Akiyama⁴, Taro Kishida³

Affiliations

¹ Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan; South Ehime Fisheries Research Center, 1289-1 Funakoshi, Ainan, Ehime 798-4292, Japan. Electronic address: syamauch@agr.ehime-u.ac.jp.
² Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
³ Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan; South Ehime Fisheries Research Center, 1289-1 Funakoshi, Ainan, Ehime 798-4292, Japan.
⁴ Advanced Research Support Center (ADRES), Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.

PMID: 27210431
DOI: 10.1016/j.bmcl.2016.05.020

Abstract

To estimate the effect of methyl group of dihydroguaiaretic acid, which shows many kinds of biological activities, on biological activity, both enantiomers of 9'-dehydroxyimperanene (5, 6) and 7,8-dihydro-9'-dehydroxyimperanene (7, 8) lacking one of the methyl groups of dihydroguaiaretic acid were synthesized. (S)-7,8-Dihydro-9'-dehydroxyimperanene (7) showed 4-6-fold higher cytotoxic activity than all stereoisomers of dihydroguaiaretic acid (2-4). The IC50 values of (S)-7,8-dihydro-9'-dehydroxyimperanene (7) against HL-60 and HeLa cells were 6.1μM and 5.6μM, respectively. Though only one of three stereoisomers of dihydroguaiaretic acid showed antibacterial activity against a gram negative bacterium, both enantiomers of 5-8 showed antibacterial activity against a gram negative bacterium. This is a Letter on biological activity of 9-norlignan, in which one of methyl groups of lignan is absent.

Keywords: Imperanene; Lignan; Norlignan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / pharmacology*
Antifungal Agents / chemical synthesis
Antifungal Agents / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Guaiacol / analogs & derivatives*
Guaiacol / chemical synthesis
Guaiacol / pharmacology*
HL-60 Cells
HeLa Cells
Humans
Inhibitory Concentration 50
Lignans / chemical synthesis
Lignans / pharmacology
Listeria / drug effects
Mitosporic Fungi / drug effects
Salmonella arizonae / drug effects
Staphylococcus aureus / drug effects
Stereoisomerism
Structure-Activity Relationship

Substances

7,8-dihydro-9'-dehydroxyimperanene
9'-dehydroxyimperanene
Anti-Bacterial Agents
Antifungal Agents
Antineoplastic Agents
Lignans
Guaiacol