27876-94-4

Basic information

• Product Name: 8,8'-DIAPOCAROTENEDIOIC ACID
• Synonyms: CROCETIN;CROCETIN, TRANS-;8,8'-DIAPOCAROTENEDIOIC ACID;2,6,11,15-TETRAMETHYLHEXADECA-2,4,6,8,10,12,14-HEPTAENEDOIC ACID;TRANS-CROCETIN;8,8'-diapo-psi,psi-carotenedioic acid;8,8'-Diapo-ψ,ψ-carotene-8,8'-dioic acid;Alpha-Crocetin
• CAS NO: 27876-94-4
• Molecular Formula: C₂₀H₂₄O₄
• Molecular Weight: 328.4
• EINECS: 248-708-0
• Product Categories: Carotenoids
• Mol File: 27876-94-4.mol
• Article Data: 9

Chemical Properties

• Melting Point: 285°
• Boiling Point: 386.14°C (rough estimate)
• Flash Point: 321.7 °C
• Appearance: Red solid
• Density: 1.0786 (rough estimate)
• Vapor Pressure: 3.32E-15mmHg at 25°C
• Refractive Index: 1.4434 (estimate)
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• Solubility: DMSO (Slightly, Heated), Methanol (Slightly)
• PKA: 4.39±0.19(Predicted)
• Stability: Light Sensitive
• CAS DataBase Reference: 8,8'-DIAPOCAROTENEDIOIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 8,8'-DIAPOCAROTENEDIOIC ACID(27876-94-4)
• EPA Substance Registry System: 8,8'-DIAPOCAROTENEDIOIC ACID(27876-94-4)

Safety Data

• Hazardous Substances Data: 27876-94-4(Hazardous Substances Data)

Usage

Uses

Used in Cardiovascular Applications:
8,8'-DIAPOCAROTENEDIOIC ACID is used as an experimental treatment for arteriosclerosis by increasing oxygen diffusion through arterial walls, thus decreasing the buildup of cholesterol.
Used in Anticancer Applications:
Crocetin, a carotenoid derived from saffron, is used as an anticancer agent, showing effects in both human adenocarcinoma gastric cancer cells and rat models of gastric cancer.
Used in Dietary Supplements:
8,8'-DIAPOCAROTENEDIOIC ACID is used as an anti-fatigue dietary supplement due to its natural carotenoid properties found in the crocus flower.

Anticancer Research

It is a natural apocarotenoid dicarboxylic acid obtained from saffron, and saffron isa spice from the flower of the Saffron crocus and present in the dry stigmas of theplant Crocus sativus which can be used as a food colorant. It is reported to be anovel anticancer agent against hepatocellular carcinoma, pancreatic cancer, lungcancer, skin carcinoma, breast cancer, and colorectal cancer. It inhibits the nucleicacid synthesis, enhances antioxidant system, induces apoptosis, hinders growthfactor signaling pathways, and thus affects the growth of cancer cells. It showseffects in the reduction of LPS-induced nitric oxide release; in the reduction ofproduced IL-1β, TNF-α, and intracellular ROS; in the activation of NF-κB; and inthe blockade of LPS (Wang et al. 2012; Gutheil et al. 2012).

InChI:InChI=1/C20H24O4/c1-15(11-7-13-17(3)19(21)22)9-5-6-10-16(2)12-8-14-18(4)20(23)24/h5-14H,1-4H3,(H,21,22)(H,23,24)/b6-5+,11-7+,12-8+,15-9-,16-10+,17-13-,18-14-

Upstream product

• 55750-86-2 crocin-4 
• 6622-76-0 methyl (E)-2-methyl-2-butenoate 
• 64603-92-5 sodium (2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioate 
• 5892-54-6 Crocetindimethylester 
• 80-59-1 Tiglic acid 
• 5056-17-7 (2E,4E,6E)-2,7-dimethyl-2,4,6-octatrienedial 
• 113951-62-5 (2E,4E,6E)-2,6-dimethylocta-2,4,6-triene-1,8-diol 
• 64768-01-0 diethyl 2,7-dimethyl-2(E),4(E),6(E)-octatriene-1,8-dioate 
• 130121-15-2 Ethyl (2E,4E)-2-methyl-6-oxohexa-2,4-dienoate 
• 129144-90-7 2-methyl-4-(triphenyl-λ⁵-phosphoranylidene)but-2-enoic acid methyl ester 
• 121666-37-3 <3-(Methoxycarbonyl)-2-butenyl>triphenylphosphoniumbromid 
• 42553-65-1 crocin 
• 35482-80-5 (2E,4E,6E,10E,12E,14E)-2,6,11,15-Tetramethyl-hexadeca-2,4,6,10,12,14-hexaen-8-ynedioic acid ethyl ester 2-formyl-2-hydroxy-1,3,3-trimethyl-cyclohexyl ester 

Downstream Products

• 5892-54-6 Crocetindimethylester 

Relevant articles and documents

Trans-crocin 4 is not hydrolyzed to crocetin following i.p. administration in mice, while it shows penetration through the blood brain barrier

A novel, fit-for-purpose, highly sensitive, analytical UPLC-PDA methodology was developed and fully validated, according to ICH, FDA and EMA guidelines, for the rapid and accurate quantification of trans-crocin 4 (TC4) and crocetin (CRC) in mice plasma and brain after i.p. administration. A PDA based methodology shows a wider applicability as it is cost effective and can be easily and seamlessly adopted by the pharma industry. The separation of the analytes was performed on a C18 Hypersil Gold column with 2.5 min run time, employing the internal standard (ISTD) methodology. The two methods were successfully applied for the determination of CRC and TC4 in mouse plasma and brain after i.p. administration of TC4 (50 mg/kg) in a time range of 0–240 min. Due to the selection of i.p. administration route, the first-pass metabolism and/or gastric hydrolysis were bypassed, a fact that enhanced the bioavailability of TC4. Furthermore, TC4 was found to be capable of crossing the Blood Brain Barrier (BBB) and build up levels in the mouse brain, regardless of its highly hydrophilic character. CRC was not detected in any plasma or brain sample, although it has been reported that TC4 quickly hydrolyzes to CRC after p.o. administration. Therefore i.p. administration could be used in the case of TC4 for the accurate determination of its biological role. Overall, the developed methodology offers important information about the bioavailability of TC4 in mouse plasma and for the first time, demonstrates the ability of TC4 to penetrate the BBB and localize inside the brain.

Effects of intestinal microbiota on pharmacokinetics of crocin and crocetin in male sprague-dawley rats

In addition to the hepatic metabolism, the role of intestinal microbiota in drug metabolism has been considered important in the biotransformation of xenobiotics. Crocin and its aglycone, crocetin, isolated from many plants, including the dried stigma of Crocus sativus and the fruit of Gardenia jasminoides, have been used in treatment of inflammation, cancer, and metabolic disorders. In this study, the effect of intestinal microbiota on the pharmacokinetics of crocin was studied following single oral treatment with 600 mg/kg crocin to male rats pre-treated with a mixture of antibiotics, such as cefadroxil, oxytetracycline, and erythromycin, for three consecutive days. Following crocin treatment, blood, urine, and feces were collected at various time points for evaluating pharmacokinetic characteristics of crocin and crocetin by using LC-MS. Results showed that intestinal absorption of crocin was relatively marginal when compared with that of crocetin, and that crocin metabolism to crocetin by intestinal microbiota would be a critical step for absorption. The present results clearly suggested that the in vivo pharmacological effects of crocin might be considered as the effects by its aglycone, crocetin, mainly, and that the metabolism of glycosidic natural products by intestinal microbiota should be considered to understand their pharmacodynamic actions.

Crocetin diester compound as well as preparation method and application thereof

The invention belongs to the technical field of pesticides, and provides a crocetin diester compound as well as preparation and application thereof in plant protection. It is found for the first timethat natural products crocin-1 and crocin-2 show higher anti-plant virus activity level than commercial variety virazole, can be used as a novel botanical pesticide or used as a lead compound for development, and used as the lead to design and synthesize the crocetin diester compound. An anti-plant virus activity test shows that all the compounds show activity on tobacco mosaic viruses, and particularly, the activity level of the crocetin di (4-fluorophenyl ethyl) ester is higher than that of a lead compound.

Preparation and Anti-Tobacco Mosaic Virus Activities of Crocetin Diesters

The development of antiviral agents with an original structure and noticeable effect is always in great need. Natural products are important lead compounds in the development of new pesticides. Crocin-1 and crocin-2 were effectively isolated from Gardeniae fructus and found to have higher anti-tobacco mosaic virus (TMV) activity levels than ribavirin. A series of the crocetin diester derivatives were synthesized with separated crocetin-1 as material and evaluated for their anti-TMV activities. They could be dissolved in common organic solvents as dichloromethane, ethyl acetate, tetrahydrofuran, and methanol. Compounds 5, 9, 13, 14, and 15 displayed higher activities in vivo than ribavirin. Compound 14 with significantly higher antiviral activities than lead compounds (crocin-1 and crocin-2) emerged as a new antiviral candidate.

The crocetin single-glucuronic acid synthesis method (by machine translation)

The invention relates to a metabolism in vivo product synthesis method. The method comprises the following steps: from traditional Chinese medicine fructus Gardeniae extracting the separated crocin, and crocin hydrolyzed into crocetin, to west pertains as substrate of synthetic west pertains to the fluoro, with fluoro and for D - glucuronic acid reaction to produce the target compound - crocetin single-glucuronic acid. The synthesis method principle is simple, easy to operate, low requirements on equipment, which can be widely applied. (by machine translation)

Characterization of the Saffron Derivative Crocetin as an Inhibitor of Human Lactate Dehydrogenase 5 in the Antiglycolytic Approach against Cancer

Inhibition of lactate dehydrogenase (LDH) represents an innovative approach to tackle cancer because this peculiar glycolytic metabolism is characteristic of most invasive tumor cells. An investigation into the biological properties of saffron extracts led to the discover of their LDH-inhibition properties. In particular, the most important saffron components, crocetin, was found to inhibit LDH (IC50 = 54.9 ± 4.7 μM). This carotenoid was independently produced by chemical synthesis, and its LDH-inhibition properties manifested via its antiproliferative activity against two glycolytic cancer cell lines (A549 and HeLa, IC50 = 114.0 ± 8.0 and 113.0 ± 11.1 μM, respectively). The results described in this article suggest that saffron may be a helpful alimentary component in the prevention of cancer that potentially contributes to the efficacy of approved cancer therapies.

HYDROLYSATE OF CROCIN

The present invention relates to a composition derived from the hydrolysate of plant containing crocin or the derivatives thereof. The composition includes a significant amount of crocetin monoester. The present invention also provides a method to hydrolyze crocin existing in a plant extract, and further relates to the use.

METHOD FOR THE PURIFICATION OF CROCETIN

The present invention provides an easily operated, industrially advantageous method for the production of crocetin. In more detail, the present invention relates to a method for the purification of crocetin, which comprises treating crocetin obtained by hydrolysis of crocin, which exists in a plant extract, with lower alcohol or a mixed solvent containing 50% by volume or more of lower alcohol and removing a soluble component in the solvent. The present invention also relates to a method for the purification of crocetin, which comprises dissolving crocetin obtained by hydrolysis of crocin, which exists in a plant extract, into an aprotic solvent which can crystallize crocetin and crystallizing crocetin from the solvent. The present invention makes it possible to efficiently prepare a desired purified crocetin of high purity. The purified crocetin is useful as a pharmaceutical composition, cosmetic product or skin cosmetics and can be used as an additive in food and health food.

SINGLET OXYGEN REACTIONS IN AQUEOUS SOLUTION. PHYSICAL AND CHEMICAL QUENCHING RATE CONSTANTS OF CROCIN AND RELATED CAROTENOIDS

Thermal decomposition of 3-(1,4-epidioxy-4-methyl-1,4-dihydro-1-naphthyl)propionic acid (2) has been used to measure both the physical and chemical quenching rate constants of 1O2 (kQ and kR, respectively) by water-soluble 8,8'-diapocarotenoids such as crocin (1a) and its derivatives (1b,c).The value of kQ was found to be slightly lower than the diffusion controlled rate constant in all the solvents examined, whereas kR showed strong dependence on the medium, going from ca. 108 in H2O to 106 M-1s-1 in DMF and DMSO.These findings suggest that both energy- and electron-transfer mechanisms are involved in the quenching of O2 (1Δg) by crocinoids.