Squalene oxide cyclization, mechanism

S. ferax and related sterol-producing Oomycetes synthesize lanosterol rather than cycloartenol (10) in Stage II. The mechanism of squalene-oxide cyclization to lanosterol involves a nonconcerted process in which a terminal intermediate,... 

The following reaction resembles the acid-catalyzed cyclization of squalene oxide. Propose a mechanism for this reaction. 

Although most attention has focussed on a cationic mechanism in the oxidative cyclization of squalene [20]. Breslow was concerned with the possibility that nature utilizes a free-radical pathway [21]. and studied the addition of benzoyloxy radical to trans, trani-famesyl acetate [22]. The benzoyloxy radicals generated by CuCl-catalyzed thermal decomposition and copper(II) benzoate was added to provide a termination mechanism. Excluding any intervention of a carbocationic process, Breslow obtained a tran -decalin compound (20 30% yield) bearing an exomethylene moiety. As pointed out by Breslow, despite a limited biochemical interest , this work evidenced a new synthetic reaction of considerable potential . An application shortly followed with the first example of a triple cyclization by Julia [23]. Triene isomers 40 were treated by benzoylperoxide in benzene and alforded after saponification alcohol 41 in 12% yield as a single diastereomer (relative stereochemistry confirmed by an X-ray analysis) with a similar tra 5-decalin system (A and B rings. Scheme 14). 

Propose a mechanism that explains the following transformation. (Note its similarity to the cyclization of squalene oxide to lanos-terol, as shown in The Chemistry of... Cholesterol Biosynthesis. in WileyPLUS.)... 

Ebersole, R. C., W. O. Godtfredsen, S. Vangedal, and E. Caspi Mechanism of Oxidative Cyclization of Squalene. Concerning the Mode of Formation of the 17(20) Double Bond in the Biosynthesis of Fusidic Acid by Fusidium coccineum. J. Amer. Chem. Soc. 96, 6499 (1974). 

So far we have dwelt on the over-all reaction, based on the concept of titanium (II), and the chemistry at this point appears very complicated. One would like to see some clarification of the over-all mechanism. We were pleased to find that one can, in this titanium series, eflFectively separate the complexation and the reduction steps (li). This is as important as the separation of the oxidation and the cyclization steps in the over-all conversion of squalene to lanosterol, a very knotty and complicated problem in the biological province. 

A few simple eukaryotic organisms can cyclize squalene but do not produce sterols. For example, Tetrahymena pyri-formis (a protozoan) produces tetrahymanol (14), a pentacyclic analog of lanosterol (15) (Fig. 23.1), from squalene. The mechanism of condensation of squalene (1) to tetrahymanol in Tetrahymena pyriformis does not involve squalene 2,3-oxide (2) and includes a protonation step, cyclization, and, finally, addition of hydroxyl group from the medium. The stereochemistry of the proton predicted to be incorporated at the 21p-position of the compound has been estab-... 

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