Regioselective hydroxylation

Oxidation of cedranes and their derivatives by RuCyaq. Na(104)/CCl4-CH3CN (anhydrous RUCI3 does not work) was studied thus epicedrane was hydroxylated regioselectively with retention of configuration to 8a-cedranol (Fig. 4.4), and other oxyfunctionalisations of non-activated C-H bonds in cedranes were similarly accomplished (Table 4.1, cf. mech. Ch. 1) [69]. 

A number of steroids have been regioselectively acylated ia a similar manner (99,104). Chromobactenum viscosum hpase esterifies 5a-androstane-3P,17P-diol [571-20-0] (75) with 2,2,2-triduoroethyl butyrate ia acetone with high selectivity. The hpase acylates exclusively the hydroxy group ia the 3-position giving the 3P-(monobutyryl ester) of (75) ia 83% yield. In contrast, bacillus subtilis protease (subtihsia) displays a marked preference for the C-17 hydroxyl. Candida iylindracea]i 2Lse (CCL) suspended ia anhydrous benzene regioselectively acylates the 3a-hydroxyl group of several bile acid derivatives (104). 

Castanospermine [79831-76-8] (78) contains four secondary hydroxyl groups and therefore represents a significant challenge for regioselective... 

Bu2SnO, benzene BnBr, DMF, heat, 80% yield. This method has also been used to protect selectively the anomeric hydroxyl in a carbohydrate derivative. The replacement of Bu2SnO with Bu2Sn(OMe)2 improves the process procedurally. The use of stannylene acetals for the regioselective manipulation of hydroxyl groups has been reviewed. ... 

The oxirane ring in 175 is a valuable function because it provides a means for the introduction of the -disposed C-39 methoxy group of rapamycin. Indeed, addition of CSA (0.2 equivalents) to a solution of epoxy benzyl ether 175 in methanol brings about a completely regioselective and stereospecific solvolysis of the oxirane ring, furnishing the desired hydroxy methyl ether 200 in 90 % yield. After protection of the newly formed C-40 hydroxyl in the form of a tert-butyldimethylsilyl (TBS) ether, hydrogenolysis of the benzyl ether provides alcohol 201 in 89 % overall yield. 

An impressive indication of the high regioselectivity of hydroxysteroid dehydrogenases (HSHDs) was reported for the oxidation of various hydroxyl groups at the steroid core ofbile acids [26] (Scheme 9.1). The hydroxy-substituents at positions 3, 7, and 12 could be selectively addressed depending on the hydroxysteroid... 

The nature of the nitrogen protecting group also played a significant role in the chemoenzymatic total synthesis ofepibatidine, which shall be outlined as an example for the synthetic elaboration of the regioselective biooxidation product of a nonnatural precursor. B. bassiana mediated hydroxylation of the aza-norbornane system enabled functionalization for the subsequent introduction of the pyridine system (Scheme 9.10) [82,83]. 

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