The cyclization mechanism of squalene in hopene biosynthesis: the terminal methyl groups are critical to the correct folding of this substrate both for the formation of the five-membered E-ring and for the initiation of the polycyclization reaction†

Abstract

Incubations of C(23)-norsqualenes 5 and 6, lacking one of the two terminal methyl groups, with squalene-hopene cyclase gave unprecedented products 7 and 8 having a tetrahymanol skeleton together with a neohopane skeleton 12, strongly suggesting that the two geminal methyls of squalene 1 are critical to the formation of the five-membered E-ring in hopene biosynthesis and also are required to initiate the cyclization reactions of 1 into the pentacyclic triterpenes 2 and 3.