Efficient Total Synthesis of Lissodendrin B, 2-Aminoimidazole Marine Alkaloids Isolated from Lissodendoryx (Acanthodoryx) Fibrosa.

Xianfeng Wei,Shengbiao Wan,Xuelong Hu,Rilei Yu,Tao Jiang

doi:10.3390/md18010036

Abstract

Lissodendrin B is a 2-aminoimidazole alkaloid bearing a (p-hydroxyphenyl) glyoxal moiety that was isolated from the Indonesian sponge Lissodendoryx (Acanthodoryx) fibrosa. We reported the first efficient total synthesis of Lissodendrin B. The precursor 4,5-disubstituted imidazole was obtained through Suzuki coupling and Sonogashira coupling reactions from 4-iodoimidazole. C2-azidation and reduction of the azide then provided the core structures of Lissodendrin B. Subsequent triple-bond oxidation, demethylation, and deacetylation gave the final product. The synthesis approach consists of ten steps with an overall yield of 1.1% under mild reaction conditions, and it can be applied for future analog synthesis and biological studies.

Highlights

Marine alkaloids offer significant advantages for the discovery of leading compounds because of their unique, complex structures and diverse bioactivities [1]
Efficient chemical synthesis of marine alkaloids in greater quantities is necessary for their usage in bioactivity studies. 2-aminoimidazole alkaloids, the most commonly investigated representative marine alkaloid, are found primarily in calcareous sponges, especially in the genera Leucetta and Clathrina [2,3,4,5]
A concise total synthesis of marine alkaloids Lissodendrin B was accomplished in ten steps giving an overall yield of 1.1%

Summary

Introduction

Marine alkaloids offer significant advantages for the discovery of leading compounds because of their unique, complex structures and diverse bioactivities [1]. 2-aminoimidazole alkaloids, the most commonly investigated representative marine alkaloid, are found primarily in calcareous sponges, especially in the genera Leucetta and Clathrina [2,3,4,5]. These compounds have been extensively studied because of their various biological activities, including anticancer [3,4,5], antimicrobial [2,6], antivirus properties [7,8], P-gp-mediated MDR reversal activity [9] as well as leukotriene B4 receptor [10] and epidermal growth factor (EGF) receptor antagonist activities [11]. There are two major approaches for preparation of 2-aminoimidazole compound: (1) the condensation of α-haloketone with an acetylated guanidine [12] or condensation of an α-aminoketone with cyanamide [13] and (2) functionalization of imidazole scaffold via protection, C2-amination, and deprotection [14,15]

Methods

Results

Conclusion