Angelicin

Angelicin is the parent compound in a family of naturally occurring organic compounds known as the angular furanocoumarins. Structurally, it can be considered as benzapyra-2-one fused with a furan moiety in the 7,8-position. Angelicin is commonly found in certain Apiaceae and Fabaceae plant species such as Bituminaria bituminosa. It has a skin permeability coefficient (LogKp) of -2.46. The maximum absorption is observed at 300 nm. The 1HNMR spectrum is available; the infrared and mass spectra of angelicin can be found in this database. The sublimation of angelicin occurs at 120 °C and the pressure of 0.13 Pa. Angelicin is a coumarine. Angelicin is the parent compound in a family of naturally occurring organic compounds known as the angular furanocoumarins. Structurally, it can be considered as benzapyra-2-one fused with a furan moiety in the 7,8-position. Angelicin is commonly found in certain Apiaceae and Fabaceae plant species such as Bituminaria bituminosa. It has a skin permeability coefficient (LogKp) of -2.46. The maximum absorption is observed at 300 nm. The 1HNMR spectrum is available; the infrared and mass spectra of angelicin can be found in this database. The sublimation of angelicin occurs at 120 °C and the pressure of 0.13 Pa. Angelicin is a coumarine. Humans have used plants rich in angelicin for centuries. The earliest known record dates back to 3000 BC when ancient Egyptians applied the oil and sap of local Apiaceae species exposing their skin to sunlight to cure vitiligo. In meantime, tribes in India used Psoralea corylifolia which contained psoralen, the isomer of angelicin. Humans also attempted to harvest the plants as an alternative food source. However, most of them turned out to be unpalatable and toxic such as Angelica archangelica due to the ability to irritate skin and damage internal organs. The name 'angelicin' stems from the aforementioned plant, Angelica. This Latin name originated in medieval Europe where this plant was also used as a universal treatment to many types of disease not mentioning the bubonic plague. At this time, people believed that the plant could prevent the soul from being taking over by sorcery, curse and evil spirit (add reference). Angelica would have appeared in a dream with an angel explaining its applications, hence the name. Ironically, it was later discovered that the plant's oil is toxic when utilized in large quantities particularly when the plant was fresh. The species of plants where angelicin is found was introduced in Britain in the 19th century. Currently, it can be found in Canada and some parts of the United States and Europe. Because of the toxicity of certain plant parts and the ability of plant to proliferate, it is included in the list of invasive species. The leaves of Angelica archangelica, which are rich in angelicin, are used to extract the compound. There were multiple studies on the toxicity of angelicin one of which showed that the compound elicits chromosomal damage in hamster cells exposed to 320-380 nm UV light. The chromosomal aberrations were shown to be also induced in humans. Nowadays, it is debated whether Angelica should be considered toxic. However, it is certain that the toxicity is dependent on the dose of angelicin administered and is solely the matter of experts when it comes to its application. The biosynthesis of angelicin can be described as a variation in the biological synthesis of furanocoumarins. It begins from the capture of organic carbon by photosynthesis and the formation of carbohydrates. Subsequently, the carbohydrates become the substrates of the shikimic acid pathway where they are converted to phenylalanine and tyrosine. Enzymes such as ammonialyases, methylases and hydroxylases then transform these amino acids to cinnamic acid derivatives which undergo o-hydroxylation yielding coumarins. The coumarins can undergo further reactions such as prenylation and oxidation to give multiple furanocoumarins one of which is angelicin. Here, the biosynthesis of angelicin is described in more detail starting at L-phenylalanine as a precursor. The phenylalanine undergoes a non-oxidative deamination by phenylalanine ammonia-lyase (PAL) to trans-cinnamic acid. Afterwards, the trans-cinnamic acid is hydroxylated at the para position by trans-cinnamate 4-monooxygenase (C4H) which utilizes NADPH, H+ and O2. The product, p-coumaric acid, is then converted to umbelliferone, the important intermediate of biosynthesis pathway. 4-Coumaric acid 2-hydroxylase (C2’H) hydroxylates the p-coumaric acid at the ortho position. Notably, this reaction uses alpha-ketoglutarate which is reduced to succinate both of which are involved in the Krebs cycle. The newly formed trans-dihydrocinnamic acid undergoes a photochemical isomerization to a cis isomer which spontaneously lactonizes to yield umbeliferone.