Enantio-specific oxidation

Enantiomerically pure sulfoxides are important intermediates in organic synthesis (21) and quite a number of pharmaceuticals and other biologically active compounds harbor a chiral sulfoxide unit (22). With respect to oxidation catalysis, enantiomerically enriched sulfoxides can either be accessed by asymmetric sulfoxidation of prochiral thioethers (Scheme 7, path a), or by kinetic resolution of racemic sulfoxides (Scheme 7, path b). For the latter purpose, enantio-specific oxidation of one sulfoxide enantiomer to the sul-fone, followed by separation, is the method of choice. 

LOX-catalyzed oxidation of LDL has been studied in subsequent studies [26,27]. Belkner et al. [27] showed that LOX-catalyzed LDL oxidation was not restricted to the oxidation of lipids but also resulted in the cooxidative modification of apoproteins. It is known that LOX-catalyzed LDL oxidation is regio- and enantio-specific as opposed to free radical-mediated lipid peroxidation. In accord with this proposal Yamashita et al. [28] showed that LDL oxidation by 15-LOX from rabbit reticulocytes formed hydroperoxides of phosphatidylcholine and cholesteryl esters regio-, stereo-, and enantio-specifically. Sigari et al. [29] demonstrated that fibroblasts with overexpressed 15-LOX produced bioactive minimally modified LDL, which is probably responsible for LDL atherogenic effect in vivo. Ezaki et al. [30] found that the incubation of LDL with 15-LOX-overexpressed fibroblasts resulted in a sharp increase in the cholesteryl ester hydroperoxide level and a lesser increase in free fatty acid hydroperoxides. 

In the interim period, results have accumulated steadily, in endeavors to address and extend the chemistry beyond the initial perceived limitations. These limitations include the following (a) the effective catalytic syntheses are confined to the reactions utilizing catecholborane (b) the scope of alkenes for which efficient rate, regio- and enantio-selectivity can be achieved is limited, and (c) the standard transformation mandates the oxidation of the initially formed (secondary) boronate ester to a secondary alcohol, albeit with complete retention of configuration [8]. Nonetheless, for noncatalytic hydroboration reactions that lead to the formation of a trialkylborane, a wide range of stereo-specific transformations may be carried out directly from the initial product, and thereby facilitate direct C-N and C-C bond formation [9]. 

While the strategy developed for the synthesis of epiquinamide by Chandrasekhar et al. could in principle have produced either enantiomer of the alkaloid, the specific example reported was of the (—)-antipode, efji-2104 (Scheme 275) The flexibihty in their route is due to Sharpless asymmetric dihydroxylation of the dienoate 2179, which was prepared in four steps fi-om hexane-1,6-diol (not illustrated). With TUD-mix-a as oxidant, the (S,S)-(—)-diol 2180 was formed in 80% yield and better than 98% enantio-selectivity stereocomplementary results were obtained from AD-mix-p, which produced the enantiomeric diol (+)-eni-2180. Hydrogenation of (—)-2180 over a palladium—carbon catalyst followed by heating with potassium carbonate afforded the butyrolactone (+)-2181, the secondary alcohol of which was tosylated before rmdergoing Sn2 substitution with an azide ion to give 2182. Replacement of the TBS ether by a mesyl ester then set the... 

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