Boswellia

Al-Harrasi, Ahmed, Khan, Abdul Latif, Rehman, Najeeb Ur, Rene & Csuk, 2021, Biosynthetic diversity in triterpene cyclization within the Boswellia genus, Phytochemistry (112660) 184, pp. 1-23 : 10

4.2. Biosynthesis of different classes of Boswellia triterpenes

Biosynthetically, the biogenesis of gem-dimethyl cyclobutanes can be traced back to geranyl pyrophosphate and/or its longer chain analogues, which ultimately originate from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). The biosynthesis of the historic precursor β- amyrin (10) commences at the chair–chair –- chair–boat conformation of (3 S)-2,3-oxidosqualene A (Scheme 1). This conformation allows it to cyclize to the corresponding 6.6.6.5-fused tetracyclic dammarenyl C20 cation B from which a group of dammarane terpenes were isolated (Scheme 2) (Fattorusso et al., 1985). A series of enzymatically driven reactions included a concerted hydride shift from C13 to C17, a C18 methyl group shift from C14 to C13, a C30 methyl group shift from C8 to C14 and the base abstraction of the C9 proton to construct the double bond between C8 and C9, leading to tirucallane-type structures and consequently the isolation of a few tirucallic acids (Scheme 3) (Pardhy and Bhattacharyya, 1978a). Approximately 34 lupane structures, including lupeolic acids, were isolated from various Boswellia species (Schemes 4 and 5) ( Proietti et al., 1981). Their biosynthetic formation involved ring D expansion, electrophilic addition on the terminal double bond of the tetracyclic baccharenyl cation C, and the construction of five-membered ring E to form lupanyl cation D. This reaction cascade proceeds to oleanyl cation F and then the oleanane derivatives (Scheme 6) (Mannino et al., 2016) by ring E enlargement, which occurs by the C30 shift from C20 to C19. Oleanyl cation F undergoes three major steps, including sequential 1,2-hydride shifts from C18 to C19 and from C13 to C18 and an elimination of H-12 to afford 6.6.6.6.6-fused pentacyclic ursane derivatives (Schemes 7 and 8) (Reddy et al., 2003). Notably, β- amyrin (10), the precursor for α- boswellic acid, is oleanane and α- amyrin (9), and the precursor for β- boswellic acid is ursane. The C-24 oxidation of 9 and 10 then afforded β- BA and α- BA, respectively (Schemes 9–11) (Culioli et al., 2003; Schweizer et al., 2000). In a similar manner, the C-24 oxidation of 9 afforded 3- epi --β- boswellic acid (1) (Schemes 9–11) (Shah et al., 2007). It is envisioned that a similar oxidation of 10 will furnish 3- epi -α- boswellic acid (5). However, this compound has not been reported to date (Al-Harrasi et al., 2018b).