E161g is a chemical compound, an ingredient included in the list of European food additives as a colouring agent. Its chemical name is canthaxanthin, a di-ketocarotenoid also known as β,β-carotene-4,4′-dione.

Canthaxanthin, which is readily available in algae, flamingos, mushrooms and crustaceans, has a characteristic orange-red colour and is the basis for the production of a commercially relevant ketocarotenoid, astaxanthin.

Chemical Industrial Synthesis Process

• Preparation of reagents. The main raw materials include acetone, acetylene, and hydrogen, as well as catalysts like palladium on carbon.
• Synthesis of intermediates. The production of canthaxanthin begins with the synthesis of key intermediates, such as β-apo-8'-carotenoic acid, obtained through specific chemical reactions.
• Condensation. The synthesized intermediates are reacted in a condensation reaction to form the basic structure of canthaxanthin. This reaction often involves the use of strong bases and controlled reaction conditions.
• Cyclization. The basic structure is further elaborated through cyclization reactions that form the conjugated ring system characteristic of canthaxanthin.
• Hydrogenation. The molecule is subjected to hydrogenation in the presence of a catalyst, such as palladium on carbon, to stabilize the structure and obtain the final form of canthaxanthin.
• Purification. The crude canthaxanthin product is purified using techniques such as crystallization, chromatography, and filtration to remove impurities and achieve a high-purity product.
• Stabilization. The purified canthaxanthin is stabilized to ensure its stability during transportation and storage, preventing oxidation and degradation.
• Quality control. The canthaxanthin undergoes rigorous quality testing to ensure it meets standards for purity, efficacy, and safety. These tests include chemical analysis, spectroscopy, and microbiological testing.

What it is used for and where

Medical

Canthaxanthin, a tetraterpene pigment, has antioxidant (1) and skin regenerating properties and can be considered a vitamin A intermediate with immune system boosting capabilities (2).

Commercially it would be an interesting product, but its use is limited by its poor solubility due to its lipophilic nature and instability (3).

Food

It is used as a food colouring, an ingredient included in the list of European food additives as E161g.

Safety

This study considers that Canthaxanthin may have some undesirable effects on human health, in particular some toxicity towards the macula vascular system also called Canthaxanthin retinopathy (4).

Molecular Formula  C₄₀H₅₂O₂

Molecular Weight  564.8 g/mol

CAS     514-78-3

UNII    4C3C6403MU

EC Number  208-187-2

Synonyms:

• E 161g
• CI 40850
• Food orange 8
• Canthaxanthine

References_____________________________________________________________________

(1) Rebelo BA, Farrona S, Ventura MR, Abranches R. Canthaxanthin, a Red-Hot Carotenoid: Applications, Synthesis, and Biosynthetic Evolution. Plants (Basel). 2020 Aug 15;9(8):1039. doi: 10.3390/plants9081039.

Abstract. Carotenoids are a class of pigments with a biological role in light capture and antioxidant activities. High value ketocarotenoids, such as astaxanthin and canthaxanthin, are highly appealing for applications in human nutraceutical, cosmetic, and animal feed industries due to their color- and health-related properties. In this review, recent advances in metabolic engineering and synthetic biology towards the production of ketocarotenoids, in particular the red-orange canthaxanthin, are highlighted. Also reviewed and discussed are the properties of canthaxanthin, its natural producers, and various strategies for its chemical synthesis. We review the de novo synthesis of canthaxanthin and the functional β-carotene ketolase enzyme across organisms, supported by a protein-sequence-based phylogenetic analysis. Various possible modifications of the carotenoid biosynthesis pathway and the present sustainable cost-effective alternative platforms for ketocarotenoids biosynthesis are also discussed.

(2) Esatbeyoglu T, Rimbach G. Canthaxanthin: From molecule to function. Mol Nutr Food Res. 2017 Jun;61(6). doi: 10.1002/mnfr.201600469.

(3) Castangia I, Manca ML, Razavi SH, Nácher A, Díez-Sales O, Peris JE, Allaw M, Terencio MC, Usach I, Manconi M. Canthaxanthin Biofabrication, Loading in Green Phospholipid Vesicles and Evaluation of In Vitro Protection of Cells and Promotion of Their Monolayer Regeneration. Biomedicines. 2022 Jan 12;10(1):157. doi: 10.3390/biomedicines10010157.

Abstract. In the present study, canthaxanthin was produced by biofermentation from Dietzia natronolimnaea HS-1 (D. natronolimnaea) and was loaded in phospholipid vesicles prepared with natural component using an easy and low dissipative method. Indeed, glycerosomes, hyalurosomes, and glycerohyalurosomes were prepared by direct hydration of both phosphatidylcholine and the biotechnological canthaxanthin, avoiding the use of organic solvents. Vesicles were sized from 63 nm to 87 nm and highly negatively charged. They entrapped a high number of the biomolecules and were stable on storage. Canthaxanthin-loaded vesicles incubated with fibroblasts did not affect their viability, proving to be highly biocompatible and capable of inhibiting the death of fibroblasts stressed with hydrogen peroxide. They reduced the nitric oxide expression in macrophages treated with lipopolysaccharides. Moreover, they favoured the cell migration in an in vitro lesion model. Results confirmed the health-promoting potential of canthaxanthin in skin cells, which is potentiated by its suitable loading in phospholipid vesicles, thus suggesting the possible use of these natural bioformulations in both skin protection and regeneration, thanks to the potent antioxidant, anti-inflammatory and antiageing effects of canthaxanthin.

(4) Sujak A. Interactions between canthaxanthin and lipid membranes--possible mechanisms of canthaxanthin toxicity. Cell Mol Biol Lett. 2009;14(3):395-410. doi: 10.2478/s11658-009-0010-8.

Abstract. Canthaxanthin (beta, beta-carotene 4, 4' dione) is used widely as a drug or as a food and cosmetic colorant, but it may have some undesirable effects on human health, mainly caused by the formation of crystals in the macula lutea membranes of the retina. This condition is called canthaxanthin retinopathy. It has been shown that this type of dysfunction of the eye is strongly connected with damage to the blood vessels around the place of crystal deposition. This paper is a review of the experimental data supporting the hypothesis that the interactions of canthaxanthin with the lipid membranes and the aggregation of this pigment may be the factors enhancing canthaxanthin toxicity towards the macula vascular system. All the results of the experiments that have been done on model systems such as monolayers of pure canthaxanthin and mixtures of canthaxanthin and lipids, oriented bilayers or liposomes indicate a very strong effect of canthaxanthin on the physical properties of lipid membranes, which may explain its toxic action, which leads to the further development of canthaxanthin retinopathy.