Trans-squalene oxide synthesis

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. 

Johnson et al. used their newly developed orthoester Claisen reaction to achieve a highly stereoselective total synthesis of aM-trans squalene (5)1 (Scheme 1.20. The diene diol 6 underwent Johnson-Claisen rearrangement when it was heated with ethyl orthoacetate in the presence of propionic acid for 3 h at 138 C. The diene dialdehyde 7, obtained by treatment of the resulting ester with lithium aluminum hydride followed by oxidation with Collins reagent, reacted with 2-propenyllithium to give the tetraene diol 8. The tetraene dialdehyde 9, which... 

The reaction was used for the oxidation of 2,7-dimethyl-2,6-octadiene (12) to 2,7-dimethyl-/ranj,trans-2,6-octadiene-l,8-dial (13). This is a tail-to-tail a -trans bifunctional isoprenoid synthetic unit and was used in a convenient synthesis of a -trans squalene.5... 

The first example of the synthesis of a natural product by non-enzymic cyclization of a squalene derivative has been provided by Sharpless. Picric acid-induced cyclization of eryt/iro-18,19-dihydroxysqualene-2,3-oxide (18) resulted in the formation of a mixture of products from which ( )-malabaricanediol (19) could be isolated in 7% yield. The crythro-dihydroxysqualene oxide (18) was synthesized from squalene via the internal trans-oxide (20) and erythro-dio (21). The formation of the bromo-ether (22) permitted selective epoxidation of the other terminal double bond. Zinc dust reduction of (22) followed by mild alkaline... 

A second new synthesis of squalene utilizes the observation that selenium dioxide oxidation of gem-dimethyl olefins or cis- and truns-allylic alcohols yields stereospecifically traus-aj3-unsaturated aldehydes. The olefin (4) or a mixture of cis- and truus-diols (5) were transformed by use of selenium dioxide, followed by reduction, into the truns-allylic diol (6). The corresponding bromide (7) was used to alkylate two moles of the ylide from trans-geranyltributylphosphonium bromide leading eventually to all-traus-squalene in 46% yield [from the diol (6)]. Protection of one of the p-alcohol groups of (6) as the tetrahydropyranyl ether opens the possibilities of unsymmetrical coupling and the introduction of specifically labelled fragments. 

---