Human white cells produce an enzyme called myeloperoxidase. This enzyme catalyzes the reaction between hydrogen peroxide and chloride ion to produce hypochlorous acid, HOCl, which reacts as if it were \(\mathrm{Cl}^{+} \mathrm{OH}^{-}\). When attacked by white cells, cholesterol gives a chlorohydrin as the major product. (a) Propose a mechanism for this reaction. Account for both its regioselectivity and stereoselectivity. (b) On standing or (much more rapidly) on treatment with base, the chlorohydrin is converted to an epoxide. Show the structure of the epoxide and a mechanism for its formation. This epoxide is believed to be involved in induction of certain cancers.

To propose the mechanism, let's first look at the reactants and reagents involved: 1. Cholesterol - a steroid with a hydroxyl group at the 3rd carbon atom. 2. Myeloperoxidase - an enzyme that catalyzes the reaction between hydrogen peroxide and chloride ion. 3. Hydrogen peroxide (H2O2) and chloride ion (Cl-) - converted by myeloperoxidase into hypochlorous acid (HOCl). The mechanism can be described in the following steps: 1. The enzyme myeloperoxidase converts hydrogen peroxide (H2O2) and chloride ion (Cl-) into hypochlorous acid (HOCl). 2. The reactive species, \(\mathrm{Cl}^{+}\), generated from HOCl, attacks the hydroxyl group at the 3rd carbon atom of cholesterol, forming a bond with the oxygen atom. This results in a chloronium intermediate. 3. The neighboring pi bond in the ring system of cholesterol attacks the chloronium ion to form a bond with the positive chlorine atom. This results in regioselectivity, giving preferential attack at the most stable carbon position in the ring system. 4. The reaction is stereoselective because the chloride ion adds to the same side of the molecule as the initial hydroxyl group, giving an anti-addition product, which is the chlorohydrin.

When the chlorohydrin either stands or is treated with base, the hydroxyl group (\(\mathrm{OH}^{-}\)) attacks the adjacent chlorine atom, leading to the formation of an epoxide and the release of a chloride ion. The mechanism for this reaction is as follows: 1. Under basic conditions, the hydroxyl group in the chlorohydrin is deprotonated, generating an alkoxide ion. 2. The alkoxide ion attacks the adjacent chlorine atom through an intramolecular nucleophilic substitution reaction (SN2), breaking the carbon-chlorine bond and forming a three-membered epoxide ring. 3. The chloride ion is released as a leaving group. The structure of the epoxide formed will have the three-membered ring formed at the same position where the chlorohydrin was initially formed, maintaining the stereochemistry of the original cholesterol molecule. This epoxide is believed to be involved in the induction of certain cancers.