An efficient synthesis of cholesterol formate

Abstract

Cholesterol formate is an important compound in the chemistry of steroids. It is used in biochemical investiga tions of model membrane vesicles.1 Recently, cholesterol formate has been isolated from the red alga Grateloupia turuturu Yamada and this may be of chemotaxonomic sig nificance for this organism.2 This compound is employed as a component in liquid crystal optical filters.3 Formyl protection is widely used in cholesterol chemistry because of its selective removal under mild conditions (K2CO3, methanol, 20 °C) in the presence of other ester protecting groups.4 That is why a search for new convenient routes to cholesterol formate is of relentless interest. Common reagents employed for O formylation of cho lesterol include DMF—benzoyl chloride,5 DMF—tri arylphosphine—halogen,6 EtOCHO—Cu(NO3)2•3H2O, 7 MeOCHO—Ph3P—CBr4, 8 CCl3CHO—K2CO3, 9 EtOCHO—PCl3—SiO2), 10 and DMF—POCl3. 11 Usual ly, they are used in large molar excesses with respect to cholesterol. For instance, formylation of cholesterol with DMF—POCl3 (the Vilsmeier complex), which is poorly reproducible and inefficient for alcohols,5 is carried out in the presence of its four to fivefold molar excess (~20 °C, 3 h, 64% yield).11 In our recent synthesis of 1 vinylpyrrole 2 carbalde hydes,12 we found that the complex DMF—oxalyl chlo ride is a milder and more efficient formylating reagent than the classic Vilsmeier system. Our investigations in the borderland between the chem istry of pyrroles and steroids,13 including novel approach es to their vinylation14 and formylation,12,15 led us to a con venient and efficient route to cholesterol formate. At a molar ratio cholesterol : DMF—oxalyl chloride of 1 : 1.5, the re action in CH2Cl2 at ~20 °C is completed in 40 min to give the target product in 97% yield (Scheme 1).