Protosteryl cation

The fourth and final cyclization occurs by addition of the C13 cation to the 17,20 double bond, giving the protosteryl cation with 17jB stereochemistry. 

Carbocation formation is initiated by epoxide ring opening in squalene oxide, giving a tertiary carbocation, and this is transformed into the four-ring system of the protosteryl cation by a series of electrophilic addition reactions (see Box 8.3). 

The resultant protosteryl cation has a tertiary carbocation in the side-chain, and a hydride shift generates another tertiary cation. A second hydride shift follows, then two methyl shifts, each time generating a new tertiary cation. 

Mechanism-based irreversible inhibitors and mutational analysis with OSCs have shown that the highly conserved amino acid motif DCTAE is required for substrate binding [27,46,57-59] (Table 3), and the conserved aspartate residue within this motif (D456) has been implicated as the likely electrophilic activator in the generation of the protosteryl cation for LS [57, 58, 60]. Similar experiments indicate that two aspartate residues at the homologous position of the... 

An additional feature of the protosteryl cation is that the C-10 methyl and H-5 also share an anti-axial relationship, and are also susceptible to Wagner-Meerwein rearrangements, so that the C-9 cation formed in the cycloartenol sequence may then initiate further migrations. This can be terminated by formation of a 5,6-double... 

Step 4 of Figure 27.14 Final Cyclization The fourth and last cy clization occurs in step 4 by addition of the cationic center at C13 to the 17,20 double bond, giving what is known as the protosteryl cation. The side-chain alkyl group at... 

Through a series of cyclizations, squalene oxide (C30) affords lanosterol in animals and fungi and cycloartenol in plants (Fig. 19). In both instances, the intermediate is a protosteryl cation that can also undergo a series of Wagner-Meerwein rearrangements to afford the cytotoxic cucurbitacins of melons and cucumbers. Squalene oxide in a chair-chair-chair-boat conformation yields the dammarenyl cation, a parent of numerous triterpene skeleta (e.g., lupane, oleanane, ursane, and taraxerane) contained in the saponins found in many foodstuffs, in soaps, and in several... 

Step 3 Cyclization of the carbocation formed in step 2 gives a tetracyclic carbocation (protosteryl cation). 

Step 4 Rearrangement and deprotonation of protosteryl cation gives the tetracyclic triterpene lanosterol. 

Ring-expanded tricyclic carbocation Protosteryl cation... 

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