Description
Brazilin is an isoflavonoid originally isolated from
C. sappan that has diverse biological activities, including neuroprotective, anti-inflammatory, antibacterial, and antioxidant properties. Brazilin inhibits Aβ (1-42) fibrillogenesis (IC
50 = 1.5 μM) more potently than (-)-epigallocatechin gallate , cucurmin , and resveratrol. It also prevents remodeling of mature Aβ (1-42) fibrils. Brazilin inhibits the production of cytokines, including PGE
2 and TNF-α (IC
50s = 12.6 and 87.2 μM). It is effective against Gram-positive and Gram-negative bacteria with MICs ranging from 31.3 to 250 μg/ml. In addition, brazilin inhibits osteoclast differentiation mediated by RANKL and is protective against LPS-induced osteoporosis in mice at a dose of 100 mg/kg.
Brazilin family of natural products.
Chemical Properties
Brazilin is obtained from Brazilwood, a tree belonging to the genus Caesalpinia in the family Fabaceae. It is an amber-coloured crystalline compound that turns orange upon exposure to air and light. It decomposes at temperatures above 130 °C. Brazilin is readily soluble in ethanol and diethyl ether and is also soluble in water. Its aqueous solution is colourless but gradually turns red upon exposure to air. In alkaline solution, it develops a red colour and is readily oxidised to form the coloured compound brazilein.
Uses
inhibits platelet aggregation, PLA2, PKC, protein phosphatase, insulin receptor kinase, nitric oxide synthase, antineoplastic
Uses
Brazilin is a hair dyeing composition that comprises a natural dye and fatty amine.
Uses
Chiefly as a dye. Has also been recommended as indicator in acid-base titrations; acids = yellow, alkalies = carmine-red.
Definition
ChEBI: Brazilin is a tertiary alcohol, a member of catechols and an organic heterotetracyclic compound. It has a role as an antioxidant, a biological pigment, an antibacterial agent, an antineoplastic agent, a hepatoprotective agent, an anti-inflammatory agent, an apoptosis inducer, a NF-kappaB inhibitor, a plant metabolite and a histological dye.
Preparation
(±)-Brazilin was synthesized through a concise nine-step sequence starting from 2-(3-hydroxyphenyl)acetic acid. The carboxylic acid was first converted into the corresponding diazoketone, which underwent a regioselective Rh₂(OAc)₄-catalysed intramolecular aryl C–H insertion to afford the indenone framework. Subsequent nucleophilic addition of a benzyl-protected aryl organolithium reagent furnished the key phenolic intermediate. Oxidation of this phenol with o-iodoxybenzoic acid (IBX) generated the corresponding o-quinone, which was reduced to the catechol derivative and then tautomerised under basic conditions to a p-quinone methide intermediate. Intramolecular aryl cyclisation of the p-quinone methide constructed the tetracyclic brazilin skeleton, and final hydrogenolytic removal of the benzyl protecting group (H₂, Pd/C) afforded (±)-brazilin. The overall strategy featured a regioselective dirhodium-catalysed aryl C–H insertion, IBX-mediated phenol-to-o-quinone oxidation, quinone methide formation, and intramolecular cyclisation as the key transformations.
Purification Methods
Brazilin crystallises from EtOH as yellow crystals which become orange when exposed to light and air, and is yellow in dilute acid but crimson in dilute alkali. When crystallised from H2O, it has m 247-248o. It forms coloured metal salts and is oxidized in air to Brazilein the quinonoid form. The (±)-form has been resolved, and the (+)-enantiomer has [] 20 +121o (c 1, MeOH). [Craig et al. J Org Chem 30 1573 1965,Morsingh & Robinson Tetrahedron 26 281 1970, Beilstein 17 H 194, 17 II 244, 17 III/IV 2711.]
References
[1] HYUNJI LEE. Brazilin Limits Inflammatory Responses through Induction of Prosurvival Autophagy in Rheumatoid Fibroblast-Like Synoviocytes.[J]. PLoS ONE, 2015: e0136122. DOI:
10.1371/journal.pone.0136122[2] WEN-JIE DU. Brazilin inhibits amyloid β-protein fibrillogenesis, remodels amyloid fibrils and reduces amyloid cytotoxicity.[J]. Scientific Reports, 2015: 7992. DOI:
10.1038/srep07992[3] SUPINYA TEWTRAKUL. Antiinflammatory and Wound Healing Effects of Caesalpinia sappan L.[J]. Phytotherapy Research, 2015, 29 6: 850-856. DOI:
10.1002/ptr.5321[4] NILESH PRAKASH NIRMAL Pharkphoom P. Antioxidant, antibacterial, and anti-inflammatory activities of standardized brazilin-rich Caesalpinia sappan extract.[J]. Pharmaceutical Biology, 2015, 53 9: 1339-1343. DOI:
10.3109/13880209.2014.982295[5] JINHEE KIM . Inhibitory effect of brazilin on osteoclast differentiation and its mechanism of action[J]. International immunopharmacology, 2015, 29 2: Pages 628-634. DOI:
10.1016/j.intimp.2015.09.018[6] Jung, Youngeun, and Ikyon Kim*. “Total Synthesis of Brazilin.”
The Journal of Organic Chemistry, 80 3, 2015, pp. 2001–05,
https://doi.org/10.1021/jo502745j.
[7] Huang, Yaodong, et al. “Synthesis of (±)-Brazilin Using IBX.”
Organic Letters, 7 26, 2005, pp. 5841–44,
https://doi.org/10.1021/ol0523749.
