Epoxides protonated

The second part of lanosterol biosynthesis is catalyzed by oxidosqualene lanosterol cyclase and occurs as shown in Figure 27.14. Squalene is folded by the enzyme into a conformation that aligns the various double bonds for undergoing a cascade of successive intramolecular electrophilic additions, followed by a series of hydride and methyl migrations. Except for the initial epoxide protonation/cyclization, the process is probably stepwise and appears to involve discrete carbocation intermediates that are stabilized by electrostatic interactions with electron-rich aromatic amino acids in the enzyme. 

When a better leaving group than LiNSC R (e.g., OMe) is present at the a-position, retention of the potentially useful sulfonamide moiety occurs (e. g., in the conversion of aziridine 271 into the highly functionalized amino ether 272 Scheme 5.69) [98]. It should be noted that the analogous chemistry with epoxides of allylic diethers failed this could again (see above) be possibly due to the higher pKa of the epoxide proton relative to the aziridine proton. 

In the other pathway, the migrations are in the same direction. The actual mechanism of this pathway is not certain, but an epoxide (protonated) intermediate " is one possibility ... 

Tendency for epoxide protonation. When the epoxide is formed in vivo it is believed that protonation of the oxygen occurs. This idea is supported by the fact that there are subcellular regions with high proton activity [49-52]. Protonation of an epoxide oxygen weakens the C-0 bonds and promotes ring opening [53-57]. 

Hint a carbonyl function is not essential to activate epoxidic protons was demonstrated by Cop and Tiffany 40 for cyclooctatetraeno oxide, which was shown to rearrange to 2,4,(l-cyokx)ctatrienone In the presence of lithium diethylamide in non polar media (Eq. 491),... 

The answer came from NOE experiments There were large NOEs between the 5h 4.70 axial rroton and one of the epoxide protons and between the axial methyl group and one of the protons .n the CH2OAC group. The stereochemistry is like this. 

Fig. 2 H-NMR of poly(gfycidyf methacrylate) before and after fiinctionalizatirai. Typically, the epoxide proton resonances are seen at 2.6, 2.8, and 3.2 ppm. The ring opening reaction results in the disappearance of these proton resonances. Residual solvent signals are marked with an asterisk...

The isomeric epoxides of the hydroxy-allo-isohumulones are found in the reaction mixture obtained upon boiling humulone in weak alkaline solution pH 11 during 90 minutes (5). They are separated by CCD after 2300 transfers in the two-phase system ether aqueous buffer pH 4.0. The cis isomer (110, Fig. 53) has a distribution coefficient of 0.31, the trans isomer (111, Fig. 53) of 0.47. The molecular formula is C21H30O7 and the pK/ values, as well as the UV absorption spectra indicate a five-membered ring structure (6). The most characteristic features in the H NMR spectrum are the epoxide protons between 5 3 and 5 4 and the pattern between 5 3.3 and 5 3.4, which is very often used to distinguish the cis and trans isomers (7). The triplet at 5 3.35 for the ring methine proton at C-5 indicates the cis configuration, while... 

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