Enantio- and Diastereoselective Aldol-Reaction of 2,6-Dimethylphenyl Propionate Using Titanium-Carbohydrate Complexes

Chloro(cyclopentadienyl)bis(1,2:5,6-di-O-isopropylidene-α-D -glucofuranos-3-O-yl)titanium ( 1 ) is used for the transmetallation of Li-enolates obtained from propionyl derivatives. While such Ti-enolates of ketones and hydrazones appear to be unreactive, the (E)enolate 13 of 2,6-dimethylphenyl propionate ( 11 ) adds to the re-side of aldehydes, affording various syn-aldols 14 with high dia- and enantioselectivity (92–97% ds, 91–97% ee, cf. Scheme 2 and Table 1). Racemic syn-aldols (±)- 14 are obtained analogously from the achiral bis(2-propyloxy)-Ti-enolate 15 (Scheme 2 and Table 2). In contrast to the unstable Li-enolate 10 , the Ti-enolates 13 and 15 isomerize at ?30°, presumably to the thermodynamically more stable (Z)-enolates (Scheme 4), While the diastereoselectivity of the achiral enolate 15 is lost upon this equilibration, the chiral (Z)-enolate 27 quite unexpectedly affords anti-aldols 12 of high optical purity (94–98% ec) and, in most cases, with acceptable-to-good diastereoselectivity (82–90% ds). Notable exceptions are branched unsaturated and aromatic aldehydes which form a greater proportion of synepimers of moderate optical purity (Scheme 5 and Table 3). Consistent with these findings, re-facial-and ami -selective aldol-addition is also exhibited by the (Z)-configurated Ti-enolate 22 of N-propionyl-oxazolidi-none 19 (Scheme 3).     

Trace analysis of rapamycin in human blood by micellar electrokinetic chromatography

A capillary electrophoretic method with UV detection at 278 nm has been developed for analysis of the immunosuppressant rapamycin (sirolimus) in human blood at low microgram per liter levels. Separation has been achieved in an acidic carrier electrolyte containing sodium dodecylsulfate and 30% (v/v) acetonitrile. For sample clean-up and preconcentration, an off-line solid-phase extraction step using a silica-based reversed-phase material and an on-capillary focussing technique were employed. The latter allows the injection of increased sample volumes without excessive band broadening. Although this new method is less sensitive than existing liquid chromatographic procedures combined with mass spectrometry, it is fully suited to routine analysis of rapamycin in blood from patients treated with this drug. Last but not least the low costs make it an attractive alternative to established methods.