Squalene oxide structure

Cyclization of squalene is via the intermediate squalene-2,3-oxide (Figure 5.55), produced in a reaction catalysed by a flavoprotein requiring O2 and NADPH cofactors. If squalene oxide is suitably positioned and folded on the enzyme surface, the polycyclic triterpene structures formed can be rationalized in terms of a series of cycliza-tions, followed by a sequence of concerted Wag-ner-Meerwein migrations of methyls and hydrides... 

In related work, a series of important studies have been devoted to enzymatic cyclization of unnatural lanosterol precursors. Thus both epoxides (23) and (29), despite being notably different in structure from squalene oxide (32), were transformed enzymatically into the pentanorlanosterol (33a) and dihydrolano-sterol (33b), respectively. These results lend support to the suggestion that the methyl-hydrogen migration sequence rests solidly on physico-chemical... 

Recrystallized products to constant specific activity-3- Accumulated A sterols structures confirmed by MS and PMR SO = squalene oxide. 

The biosynthesis of cholesterol from squalene was examined. Using model structures and intrinsic reaction coordinate calculations, evidence was reported for the asynchronous, concerted reaction of squalene oxide to the protosterol cation. 

Cyclization of squalene in eukaryotes is initiated by protonation of the epoxide derivative, squalene oxide 96, formed by flavin-mediated oxidation of squalene with molecular O2. A wide variety of polycychc structures with different ring sizes and stereochemistries... 

Recent mechanism studies involving incubations with stable isotopes (66,69,70) and studies by us on conformiational analysis (38-42), distribution (7), structure-function/metabolism relationships (54, 55) and mechanistic enzymology of sterol transformation (12,56), negate the otherwise attractive explanation hypothesized by Ourisson et al, (9,10) for evolution of the sterol pathway beginning with the cycloartenol-based pathway. The new data indicate that the lanosterol-based pathway may have evolved before cycloartenol-based pathway, the squalene-oxide cyclase and... 

More recently it has been shown (6, 7) that zinc dialkyl dithiophosphates also act as chain-breaking inhibitors. Colclough and Cunneen (7) reported that zinc isopropyl xanthate, zinc dibutyl dithiocarbamate, and zinc diisopropyl dithiophosphate all substantially lowered the rate of azobisisobutyronitrile-initiated oxidation of squalene at 60°C. Under these conditions, hydroperoxide chain initiation is negligible, and it was therefore concluded that inhibition resulted from removal of chain-propagating peroxy radicals. Also, consideration of the structure of these zinc dithioates led to the conclusion that no suitably activated hydrogen atom was available, and it was suggested that inhibition could be accounted for by an electron-transfer process as follows ... 

Squalene is also an intermediate in the synthesis of cholesterol. Structurally, chemically, and biogenetically, many of the triterpenes have much in common with steroids (203). It has been verified experimentally that trans-squalene is the precursor in the biosynthesis of all triterpenes through a series of cyclization and rearrangement reactions (203,204). Squalene is not used much in cosmetics and perfumery formulations because of its light, heat, and oxidative instability however, its hydrogenated derivative, squalane, has a wide use as a fixative, a skin lubricant, and a carrier of lipid-soluble drugs. 

The fungus Sclerotinia fruticola produces squalene 10,11-oxide, whose structure was confirmed" by comparison with a synthetic sample. The results of a "C study of squalene suggest" that the conformation and intramoleculaf motion do not vary greatly with the polarity of the medium. 

Barnard et al.20 presented a somewhat different picture of the involvement of sulfur compounds in oxidation inhibition involving olefinic hydrocarbons. They studied the oxidation of squalene (an olefin) in the presence of sulfur compounds and concluded by careful measurement of oxygen uptake that it was not the sulfide that inhibited oxidation but the initially formed sulfoxide, and that inhibition was very dependent on the chemical structure of the sulfide. However, they did not suggest any specific mechanism for the inhibition. 

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