7380-40-7

Basic information

• Product Name: Bergamotine
• Synonyms: BERGAMOTTIN;BERGAPTIN;BERGAMOTIN;BERGAMOTINE;AKOS 214-13;5-GERANYLOXYPSORALEN;4-GERANYLOXYPSORALEN;GF-I-2
• CAS NO: 7380-40-7
• Molecular Formula: C₂₁H₂₂O₄
• Molecular Weight: 338.4
• Product Categories: Miscellaneous;Coumarins;Amines;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;standard material,plant extracts
• Mol File: 7380-40-7.mol

Chemical Properties

• Melting Point: 75-80 °C
• Boiling Point: 503.7 °C at 760 mmHg
• Flash Point: 258.4 °C
• Appearance: /
• Density: 1.153 g/cm³
• Vapor Pressure: 2.85E-10mmHg at 25°C
• Refractive Index: 1.583
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• BRN: 1353914
• CAS DataBase Reference: Bergamotine(CAS DataBase Reference)
• NIST Chemistry Reference: Bergamotine(7380-40-7)
• EPA Substance Registry System: Bergamotine(7380-40-7)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• F: 10-23
• Hazardous Substances Data: 7380-40-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Bergamottin is used as a mechanism-based inactivator for the cytochrome P450 3A4 enzyme. This application is crucial in the pharmaceutical industry because it contributes to the grapefruit juice-drug interaction, which can affect the metabolism and efficacy of certain medications. By understanding and managing this interaction, healthcare professionals can optimize drug therapy and minimize potential adverse effects.
Additionally, Bergamottin's presence in grapefruit juice may have other health-related applications, such as its potential use in dietary supplements or as a natural remedy for various conditions. However, more research is needed to fully understand its therapeutic potential and safety in these contexts.

InChI:InChI=1/C21H22O4/c1-14(2)5-4-6-15(3)9-11-24-21-16-7-8-20(22)25-19(16)13-18-17(21)10-12-23-18/h5,7-10,12-13H,4,6,11H2,1-3H3/b15-9+

Upstream product

• 6138-90-5 trans-geranyl bromide 
• 486-60-2 bergaptol 
• 484-20-8 bergapten 
• 763-10-0 geranyl diphosphate 

Downstream Products

• 206978-14-5 Epoxybergamottin 
• 264234-05-1 17,18-dihydroxybergamottin 
• 145414-76-2 6',7'-dihydroxybergamottin 
• 486-60-2 bergaptol 

Relevant articles and documents

Photo-protective effects of selected furocoumarins on β-pinene, R-(+)-limonene and γ-terpinene upon UV-A irradiation

The effect of furocoumarins on terpene photo-oxidation under UV-A light was investigated. For this purpose, four furocoumarins (8-methoxypsoralen, bergapten, bergaptol, bergamottin) each at a level of 5%, was added to solutions of the terpenes β-pinene, R-(+)-limonene and γ-terpinene in ethanol followed by UV irradiation at 366 nm. Bergaptol and bergamottin were synthesized and fully elucidated by NMR spectroscopy. UV-induced transformation of all terpenes was substantially reduced in the presence of furocoumarins. Best photo-protection was observed for γ-terpinene with the addition of bergaptol, i.e. degradation was reduced by 73% compared to the neat substance over a time period of ten days. Bergamottin (50.2%), bergapten (39.8%) and 8-methoxypsoralen (39.6%) also reduced degradation substantially. The protective effect of bergaptol was even noticeable at low concentrations of 0.1%. The main oxidation product of γ-terpinene was p-cymene. Limonene and β-pinene showed a predominated hydroperoxide formation under UV light which could almost completely prevented in the presence of furocoumarins. The protective effect of furocoumarins was presumably due to energy dissipation as a result of the conversion of high energetic radiation (UV-A) into visible light via fluorescence. Phosphorescence or self-quenching within the triplet state were further mechanisms avoiding reactions of excited furocoumarins with the terpenes under investigation. Hence, the photo-stability of the furocoumarins themselves correlated with the extent of their protective effect on all three terpenes.

Parallel evolution of UbiA superfamily proteins into aromatic O-prenyltransferases in plants

Plants produce ～300 aromatic compounds enzymatically linked to prenyl side chains via C–O bonds. These O-prenylated aromatic compounds have been found in taxonomically distant plant taxa, with some of them being beneficial or detrimental to human health. Although their O-prenyl moieties often play crucial roles in the biological activities of these compounds, no plant gene encoding an aromatic O-prenyltransferase (O-PT) has been isolated to date. This study describes the isolation of an aromatic O-PT gene, CpPT1, belonging to the UbiA superfamily, from grapefruit (Citrus × paradisi, Rutaceae). This gene was shown responsible for the biosynthesis of O-prenylated coumarin derivatives that alter drug pharmacokinetics in the human body. Another coumarin O-PT gene encoding a protein of the same family was identified in Angelica keiskei, an apiaceous medicinal plant containing pharmaceutically active O-prenylated coumarins. Phylogenetic analysis of these O-PTs suggested that aromatic O-prenylation activity evolved independently from the same ancestral gene in these distant plant taxa. These findings shed light on understanding the evolution of plant secondary (specialized) metabolites via the UbiA superfamily.

Natural oxyprenylated coumarins are modulators of melanogenesis

Naturally occurring coumarins 7-isopentenyloxycoumarin, auraptene, and umbelliprenin are able to modulate the biosynthesis of melanin in murine Melan-a cells probably through the interaction with selected biological targets like estrogen receptor β and aryl hydrocarbon receptor. Such a modulation strictly depends on the individual structure of the coumarin: the presence of a 3,3-dimethylallyloxy side chain is a structural determinant for tanning activation whereas a farnesyl one leads to the opposite effect. The parent compound with a free OH group, umbelliferone, did not provide any interaction. Other coumarins assayed, having shorter chains and/or being substituted in other positions, and prenyloxypsoralens, were not active or not further investigated in this context being cytotoxic at low doses.

Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor

The present study was demonstrated to evaluate the effects of naturally occurring coumarins (NOCs) including simple coumarins, furanocoumarins, and pyranocoumarins on the inhibition of β-secretase (BACE1) activity. Of 41 NOCs examined, some furanocoumarins inhibited BACE1 activity, but simple coumarins and pyranocoumarins did not affect. The most potent inhibitor was 5-geranyloxy-8-methoxypsoralen (31), which has an IC50 value of 9.9 μM. Other furanocoumarin derivatives, for example, 8-geranyloxy-5- methoxypsoralen (35), 8-geranyloxypsoralen (24), and bergamottin (18) inhibited BACE1 activity, with the IC50 values 25.0 μM. Analyses of the inhibition mechanism by Dixon plots and Cornish-Bowden plots showed that compounds 18, 31 and 35 were mixed-type inhibitor. The kinetics of inhibition of BACE1 by coumarins 24 was non-competitive inhibitors.

Design, synthesis and evaluation of furanocoumarin monomers as inhibitors of CYP3A4

A number of furanocoumarins isolated from grapefruit juice have been found to inhibit CYP3A4 activity in vitro. In this study, we have designed and synthesised a range of analogues based on bergamottin to investigate the relationship between chemical stru

SYNTHESIS OF SPIRO ORTHO ESTERS, SPIRO ORTHO CARBONATES, AND INTERMEDIATES

Ortho esters and ortho carbonates can be produced by alkylating esters and carbonates with, for example, the hexafluorophosphate salt of a trialkyl oxonium ion. The spiro species are useful intermediates in the synthesis of complex organic molecules. Synt

Synthesis and biological evaluation of 6',7'-dihydroxybergamottin (6,7-DHB, a naturally occurring inhibitor of cytochrome P450 3A4

The recently isolated inhibitor of cytochrome P450 CYP3A4, 6',7'-dihydroxybergamottin (6,7-DHB), was synthesized by an efficient route that is readily adaptable to the production of analogues. The compound was evaluated as an inhibitor of 3A4 in a purified enzyme preparation, as well as against human liver microsomes and human 3A4 expressed in Escherichia coil membrane. In each case, 6,7-DHB proved to be a potent NADPH- and time dependent inactivator of 3A4.