Synthesis of three bromophenols from red algae as PTP1B inhibitors

• Published in: Chinese journal of oceanology and limnology Vol. 29; no. 1; pp. 68 - 74
• Main Authors: Guo, Shuju, Li, Jing, Li, Ting, Shi, Dayong, Han, Lijun
• Format: Journal Article
• Language: English
• Published: Heidelberg SP Science Press 2011; Springer Nature B.V
• Subjects: Algae; Benzene; Biology; Bromination; Chemical synthesis; Chemistry; Colorimetry; Earth and Environmental Science; Earth Sciences; Friedel-Crafts reaction; In vivo methods and tests; Inhibitors; Marine; Natural products; Oceanography; Phosphatase; Protein-tyrosine-phosphatase; Proteins; Seaweeds; Structure-activity relationships; Synthesis; Tyrosine; 二羟基苯; 合成路线; 抑制剂; 生物活性; 蛋白酪氨酸磷酸酶; synthesis; PTP1B inhibitory activity; bromophenols
• ISSN: 0254-4059; 2096-5508; 1993-5005; 2523-3521
• DOI: 10.1007/s00343-011-9996-7

Bromophenols are a set of natural products widely distributed in seaweed, most of which exhibit interesting and useful biological activities. To develop a reliable and efficient synthetic route to these natural bromophenols, three of them, 3,4-dibromo-5-（2＇-bromo-3＇,4＇- dihydroxy-6＇-methoxymethyl- benzyl）-benzene-1,2-diol （compound 9）, 3,4-dibromo-5-（2＇-bromo-6＇-ethoxy methyl-3＇,4＇-dihydroxybenzyl）- benzene-1,2-diol （compound 10）, and 3-bromo-4-（3＇-bromo-4＇,5＇-dihydroxy benzyl）-5-（ethoxymethyl）- benzene-1,2-diol （compound 14）, isolated from red marine algae, have been synthesized in eight steps with an overall yield of 14.4%, 14.4%, and 18.2% respectively, via a practical approach employing bromination, Wolff-Kishner-Huang reduction and a Friedel-Crafts reaction as key steps. The protein tyrosine phosphatase 1B （PTP1B） inhibitory activities of the synthetic compounds were evaluated by the colorimetric assay. The results show that these compounds are moderate PTP1B inhibitors. The synthesis of these bromophenol derivatives makes in vivo studies of their structure-activity relationships and inhibition activity against PTP1B possible.