Склареол

Sclareol is a bicyclic diterpene alcohol with roles in plant growth, development, defense, and attraction of pollinators. Its molecular formula is C₂₀H₃₆O₂ and its molecular weight is 308.5. It is also named Labd-14-ene-8,13-diol. Extracted from plant matter, it is accompanied by several other diterpene alcohols of similar structure, the best known being cis-abienol and sclareolide.

Physical Properties

Sclareol is a solid that forms large crystals. It melts at 95.6 to 98.7 °C. It is practically insoluble or insoluble in water and soluble in ethanol.

Plant Sources

Salvia sclarea, the clary sage, is a biennial (short-lived) herbaceous perennial in the genus Salvia. It is native to the northern Mediterranean Basin and to some areas of north Africa and Central Asia. It reaches 0.91 to 1.22 m in height. Sclareol is mainly produced in the glandular trichomes of sage flower calyces. It is formed via a methylerythritol-phosphate biosynthetic pathway. Sclareol is mainly isolated from the inflorescences of Salvia sclarea, where it is concentrated in the oil glands of the calyces. In Salvia sclarea, sclareol accounts for about 11.5-15.7% of the essential oil. The terpenoid content of S. sclarea, sclareol included, is affected by geography, climate, temperature, carbon dioxide, nitrogen, plant lines and other factors. Sclareol is also extracted from the flowers of Cistus creticus, Nicotiana glutinosa, and Cleome spinosa. In an aromatic extraction product of Nicotiana glutinosa sclareol made up 6.9%.

Cultivation

Clary sage is cultivated in countries including Hungary, Bulgaria, Moldavia, Romania and France, where growing global demand for sclareol has encouraged new breeding initiatives. Breeding produced the variety Scalia, which has a high sclareol yield but flowers late, and then the variety Toscalia, which has a high sclareol yield without late flowering. The ornamental cultivar Vatican White produced 20% less sclareol than the cultivar used for oil production.

From Sclareol to Ambroxide

Ambroxide is a naturally occurring terpenoid and one of the key constituents responsible for the odor of ambergris. It has an ambery and woody smell historically linked to ambergris, reminiscent of tobacco and clary sage. Among the starting materials used for the semi-synthesis of ambroxide, sclareol is the most promising because of its structural similarity to ambroxide, both having a labdane carbon skeleton. The industrial route has four steps: extraction of sclareol from Salvia sclarea, oxidation of its side chain to sclareolide, reduction of sclareolide to ambradiol, and cyclodehydration of ambradiol to ambroxide. A one-pot synthesis from sclareol is viewed as convenient and environmentally friendly. Hyphozyma roseonigra converts sclareol to ambradiol, which can be converted to ambroxide by a cyclodehydration process. The route faces challenges such as the long growth cycle of the plant, its susceptibility to climate changes and the environmental issue associated with the chemical waste. A newer patented method uses homofarnesol as the raw material and was stated to require 100 times less agricultural surface than the traditional method from clary sage.

Microbial Conversion

Cryptococcus albidus converted 60 g/L of sclareol to 43 g/L of sclareolide within 5 days in a fermenter, and Filobasidium magnum converted 30 g/L to 21.62 g/L within 72 hours in flasks. A co-culture of sclareol-producing engineered yeast and Hyphozyma roseonigra gave 493.1 mg/L of ambradiol, the first complete biosynthesis of ambradiol from glucose.