Squalene-2.3-epoxide

The reactivity of epoxides toward nucleophilic ring opening is responsible for one of the biological roles they play Squalene 2 3 epoxide for example is the biological... 

Squalene monooxygenase, an enzyme bound to the endoplasmic reticulum, converts squalene to squalene-2,3-epoxide (Figure 25.35). This reaction employs FAD and NADPH as coenzymes and requires Og as well as a cytosolic protein called soluble protein activator. A second ER membrane enzyme, 2,3-oxidosqualene lanosterol cyclase, catalyzes the second reaction, which involves a succession of 1,2 shifts of hydride ions and methyl groups. 

Step 4—Formation of Lanosterol Squalene can fold into a structure that closely resembles the steroid nucleus (Figure 26-3). Before ring closure occurs, squalene is converted to squalene 2,3-epoxide by a mixed-... 

The sequence of transformations from squalene to lanosterol begins by the enzymatic oxidation of the 2,3-double bond of squalene to form (3S)-2,3-oxidosqualene [also called squalene 2,3-epoxide]. 

Cholesterol is the sterol characteristic of animal cells plants, fungi, and protists make other, closely related sterols instead. They use the same synthetic pathway as far as squalene 2,3-epoxide, at which point the pathways diverge slightly, yielding other sterols, such as stigmasterol in many plants and ergosterol in fungi (Fig. 21-37). 

SAMPLE SOLUTION (a) As the structural formula in step 5 of Figure 26.10 indicates, the double bond of cholesterol unites C-5 and C-6 (steroid numbering). The corresponding carbons in the cyclization reaction of step 1 in the figure may be identified as C-7 and C-8 of squalene 2,3-epoxide (systematic IUPAC numbering). 

As shown in the coiled form of squalene 2,3-epoxide, these correspond to hydrogens at C-14 and C-l8 (systematic IUPAC numbering). 

Tracking the 14C label of 14CH3C02H through the complete biosynthesis of cholesterol requires a systematic approach. First, by analogy with Problem 26.11, we can determine the distribution of 14C (denoted by ) in squalene 2,3-epoxide. 

Next, follow the path of the 14C-enriched carbons in the cyclization of squalene 2,3-epoxide to lanosterol. 

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