Sandalwood and Santalols – A Toast to a Legendary Fragrance

By Brian Tsui, PhD candidate in the Morris Group at the University of Toronto and Website Coordinator for the GCI

Since the earliest civilizations, perfumes have been used by humans to impart pleasant aromas to themselves and their environment. Until recently, most perfumes were derived from natural sources such as natural oils, flowers, and herbs. Perfumes of today are complex, composed of many natural and synthetic chemicals dissolved in a solvent, mainly water and ethanol, to the appropriate concentration. One of the most legendary chemical components can be found in sandalwood, which is a class of slow-growing woods found primarily in south and southeast Asia. Sandalwood is often stated to be one of the most expensive woods in the world due to its oil having the unusual property of retaining its woody and spicy aroma for decades. Some well-known fragrances that contain sandalwood oil are Crystal Noir by Versace and Hypnotic Poison by Dior (Figure 1). In addition to being used in various religions from Buddhism to Zoroastrianism, sandalwood oil has been used in Ayurvedic medicine for the treatment of somatic and mental disorders.3

Figure 1. Examples of fragrances containing sandalwood oil.1,2

Combined with the near-monopoly on the sandalwood industry by the Indian government, which was only relaxed in the late 1990s, it is not surprising that demand has outstripped supply. On the demand side, China alone is expected to account for 20,000 tonnes of sandalwood by 2025. Each harvestable sandalwood tree only produces roughly 600-700 mL of sandalwood oil, which corresponds to around $2,000 of sandalwood oil per tree. Sustainably sourced sandalwood can easily double the global market value. This high profitability has led other countries to enter the sandalwood industry, such as Australia. TFS Corp is a leading Australian producer that is expected to increase the production of sandalwood to 10,000 tonnes to meet future demands.4 The main supply challenge is that it can take up to 15 years until sandalwood is mature enough to be harvested for its oils. The slow maturation rate of sandalwood is thus heavily susceptible to disease and increasing impacts of climate change. The extraction process is also destructive by uprooting the entire tree to be physically broken down before steam distillation. Until new sandalwood farms reach harvest maturity, synthetic chemists are tasked with finding routes to this fragrance oil.

Figure 2. Main components of sandalwood oil.

Early research in 1914 by V. Paolini and Laura Vivizia at the University of Rome detailed the isolation of sandalwood oil into pure components α-santalol and β-santalol (Figure 2).5 Not to be confused for the laugh of the jolly old man who may have descended your chimney this holiday season, santalols belong to a class of sesquiterpenes, which in turn are a class of terpenes comprising of three isoprene units. It was found that the α isomer comprised roughly 55% of sandalwood oil, with the β isomer making up roughly 20%. The α isomer is purported to have most of sandalwood oil’s therapeutic properties such as increased attentiveness, anticancer properties, and topical anti-inflammation.3,6 In contrast, the β isomer provides the woody and spicy aroma characteristic of sandalwood oil. Later in 1970, Elias J. Corey and coworkers at Harvard University published the first total synthesis of α-santalol in 11.3% yield starting from (+)-3-bromocamphor (Figure 3a).7,8 Much later in 2009, Charles Fehr and coworkers at Firmenich SA reported the first total synthesis of β-santalol in 31.5% yield starting from crotonaldehyde and cyclopentadiene (Figure 3b).9 In more recent and scalable work by BASF in 2020, a fermentation process with Rhodobacter sphaeroides using cornstarch-derived sugars from European corn affords α-santalol and β-santalol in a similar ratio compared to that of natural sandalwood oil.10 Isobionics, a Dutch biotech firm focused on fermentation of aromatic compounds and acquired by BASF in 2019, demonstrates the viability of sandalwood oil production year-round with minimal waste and cost, without worrying about destructive cultivation of old sandalwood forests.

Figure 3. Retrosynthetic routes to α-santalol and β-santalol.

With global demand only increasing for this valuable oil, chemists are poised to tackle this problem to meet the religious, fragrance, and medicinal needs of today’s society. One thing is for certain: human nature will no doubt value “natural” sandalwood oil over “synthetic” sandalwood oil, even if the two products are chemically identical. Whether by increasing the cultivation of sustainable sandalwood forests for a natural product or fermentation of cheap and renewable feedstocks to afford synthetic sandalwood oil, scientists are working to ensure that these chemicals will be available to those who can stomach the cost that its unique properties demand.


  1. Versace. (accessed Dec 13, 2021)
  2. Dior. (accessed Dec 13, 2021)
  3. Heuberger, E.; Hongratanaworakit, T.; Buchbauer, G. Planta Med. 2006, 72, 792–800
  4. Quintis Sandalwood. (accessed Dec 12, 2021)
  5. Paolini, V.; Divizia, L. Atti R. Accad. Lincei 1914, 23, 226-230
  6. Bommareddy, A.; Brozena, S.; Steigerwalt, J.; Landis, T.; Hughes, S.; Mabry, E.; Knopp, A.; VanWert, A. L.; Dwivedi, C. Nat. Prod. Res. 2019, 33, 527-543
  7. Corey, E. J.; Chow, S. W.; Scherrer, R. A. J. Am. Chem. Soc. 1957, 79, 5773-5777
  8. Corey, E. J.; Kirst, H. A.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1970, 92, 6314-6320.
  9. Fehr, C.; Magpantay, I.; Arpagaus, J.; Marquet, X.; Vuagnoux, M. Angew. Chem. Int. Ed. 2009, 48, 7221-7223
  10. Bettenhausen, C. Chemical and Engineering News. (accessed Dec 11, 2021)

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