scyllo-Inositol, also called scyllitol, cocositol, or quercinitol, is a chemical compound with formula C6H12O6, one of the nine inositols, the stereoisomers of cyclohexane-1,2,3,4,5,6-hexol. The molecule has a ring of six carbon atoms, each bound to one hydrogen atom and one hydroxyl group (–OH); if the ring is assumed horizontal, the hydroxyls lie alternately above and below the respective hydrogens. scyllo-Inositol is a naturally occurring carbohydrate, specifically a sugar alcohol. It occurs in small amounts in the tissues of humans and other animals, certain bacteria, and more abundantly in some plants. Around 2000, scyllo-inositol attracted attention as a possible treatment for neurodegenerative disorders such as Alzheimer's. For this use it received the codes AZD-103 and ELND005.
Chemical and physical properties
Crystal structure Anhydrous scyllo-inositol exists in at least two polymorphs (crystal forms). In both forms the molecules have symmetry 1 ¯ {\displaystyle {\bar {1}}} and are in the chair conformation, that puts all the hydroxyls in nearly equatorial positions. The "A" form readily crystallizes from water. It has a lower density 1.57 g/ml and decomposes at 358 °C. It crystallizes in the monoclinic system with group is P 2 1 / c {\displaystyle P2_{1}/c} . The cell parameters are a = 508.9 pm, b = 664.5 pm, c = 1194.8 pm, β = 116.98°, Z = 2. The ring puckering parameter Q is 58.1 pm. The "B" form is hard to obtain in pure form, as it often crystallizes mixed with the "A" form. Its density is 1.66 g/ml and decomposes at about 360 °C. Its crystal system is triclinic with group P 1 ¯ {\displaystyle P{\bar {1}}} . The cell parameters are a = 672.5 pm, b = 679.7 pm, c = 863.5 pm, α = 95.45°, β = 99.49°, γ = 99.19°, Z = 2. The puckering Q is 56.6 pm. The density of the "A" form is similar to that of myo-inositol but about 0.05 to 0.10 g/mL lower than that of the other inositol stereoisomers, and of the "B" form. The melting (decomposition) point of both forms is the highest among all inositols. Like all of them, the crystals feature infinite chains of hydrogen bonds.
Synthesis Scyllitol and other stereo isomers can be synthesized from para-benzoquinone via a conduritol intermediate. It can also be obtained from myo-inositol by the Mitsunobu reaction. Various animals, plants, insects, and bacteria have been found to convert myo-inositol to scyllo-inositol, including Streptomyces griseus, where that conversion is part of the synthesis of streptomycin. Scyllitol was known to be a facultative intermediate in the metabolism of myo-inositol by the bacterium Bacillus subtilis. In 2011 a genetically engineered strain of this organism was developed which interrupted that pathway and converted part of the myo-inositol in the medium to scyllo-inositol in 48 hours. Eventually the process was able to produce 27.6 g/L of scyllo-inositol in the medium, from 50 g/L of myo-inositol, in 48 h. In 2021 another process was developed using the bacterium Corynebacterium glutamicum, producing 1.8 g/L of scyllitol from 20 g/L glucose and 4.4 g/L from 20 g/L sucrose in 72 h. The conversion involves NAD+-dependent oxidation of myo-inositol to 2-keto-myo-inositol (scyllo-inosose), followed by NADPH-dependent reduction to scyllitol.
Derivatives Several derivatives of scyllo-inositol have been synthesized and studied in the laboratory, such as phosphates (variants of phytic acid) and orthoformates with an adamantane structure.
Biochemistry
Natural occurrence Scyllitol is widely distributed in nature in fish, insects, mammalian tissues and urine, certain bacteria, and plants such as Calycanthus occidentalis. It is particularly abundant in coconut milk. The scyllitol derivative O-methyl-scyllo-inositol is one of the predominant soluble carbohydrate derivatives in the root nodules of the pea plant created by the bacterium Rhizobium leguminosarum, together with the isomer ononitol (4-O-methyl-myo-inositol), which are not found elsewhere in the plant. Scyllitol hexakis dihydrogenphosphate, the scyllo isomer of phytic acid (but not lower phosphates) has been detected in pasture soils from England and Wales at concentrations up to 130 mg of phosphorus per kg of soil, accounting for up to 15% of the soil organic phosphorus. The ratio of the scyllo isomer to the myo isomer ranged between 0.29 and 0.79. The concentration of scyllo-inositol in coconut milk (the fluid inside the fruit of Cocos nucifera) is 0.5 g/L, five times that of myo-inositol.
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