The Synthesis of Fragrant Natural Products from Santalum album L.: (+)-(Z)-?-Santalol and (–)-(Z)-?-Santalol

Abstract

The synthetic challenges associated with the selective synthesis of α-Santalene (1), (Z)-α-Santalol (2), β-Santalene (3), and most importantly (Z)-β-Santalol (4) have interested the world's synthetic chemists for decades. These molecules, lovely examples of nature's exquisite creations, have been isolated from East Indian Sandalwood Oil (Santalum album L.) and have stimulated chemists to develop new and efficient methodologies to synthesize them. The synthesis and evolution of various approaches to the [2.2.1]bicycloheptane ring system present in β-Santalene (3) and the even more challenging selective synthesis of the (Z)-allylic alcohol sidechain present in both (Z)-α-Santalol (2) and ((Z)-β-Santalol (4) will be covered in this review.

Synthesis of Cyclic Fragrances via Transformations of Alkenes, Alkynes and Enynes: Strategies and Recent Progress

“…As the principal fragrance of the precious sandalwood oil, (–)- β -santalol has represented an attractive target for chemists for many years [ 103 ]. In the first enantioselective total synthesis of (−)- β -santalol, accomplished by Fehr et al from Firmenich, a unique Cu-catalyzed rearrangement was incorporated [ 104 ] ( Scheme 9 ).…”

“…The cascade cyclization of multifunctional linear substrates is a step-economic way to gain access to chemical complexity from simplicity, which is a maneuverable strategy as part of Nature’s synthetic power for synthesis of fragrances. For example, the biosynthesis of terpenoids and their derivatives, such as santalol and sclareol, was deemed to include a cationic cascade cyclization and the rearrangement of a linear polyene precursor, which can also be achieved in microbial cell factories [ 103 , 147 , 148 , 149 , 150 , 151 ]. Since Johnson’s landmark synthesis of progesterone [ 152 ], the biomimetic domino cyclization of polyenes and enynes has emerged as one of the most powerful strategies for the construction of polycyclic scaffolds [ 153 ].…”

Biocatalytic approaches for a more sustainable synthesis of sandalwood fragrances

“…the α- and the β-santalol sesquiterpenes (Scheme 1A), however, so far, none of these laboratory-scale syntheses appears to be exploitable on an industrial level. 3 In this regard, very recently, Ventos has commercialized Isobionics® Santalol oil, which, in terms of composition and odorous properties, is very close to the natural one, but it is produced on a biotechnological basis from renewable raw materials (cornstarch). 4 Alternatively, a new category of synthetic sandalwood-scented fragrances ( 1 ) like Brahmanol®, Firsantol®, Sandalore®, Ebanol®, and many others was developed.…”