Stereoselective hydroxylation reactions

H L Holland, Stereoselective hydroxylation reactions, in Stereoselective Biocatalysis, R N Patel (ed), 2000, Marcel Dekker New York, p. 131-152. 

Although a significant number of hydroxylases, particularly cytochrome P450-dependent enzymes from mammalian sources, has been isolated and characterized, for the reasons discussed in Sec. I.A.l very few such enzymes are of practical value as catalysts for stereoselective hydroxylation reactions. However, two classes of readily available enzymes do have the potential to be useful catalysts neither the lipoxygenases or the peroxidases... 

It was projected that compound 13 could be stereoselectively linked, through its free phenolic hydroxyl group, with the anomeric carbon of intermediate 12 under suitably acidic conditions (see Scheme 8). Gratifyingly, the action of boron trifluoride etherate on a mixture of 12 and 13 in CH2CI2 at -50 °C induces a completely stereoselective glycosidation reaction, providing the desired a-ano-mer 48 in an excellent yield of 95 % from 46. It is presumed that boron trifluoride initiates cleavage of the anomeric trichloroacetimi-... 

In every case the information provided has been obtained by collating public domain sources of information, but unfortunately very often little data is available, particularly on commercial aspects, even for products that have proved to be big successes. Thus microbial biotransformations for steroid modification, particularly stereoselective hydroxylations, such as the use of Rhizopus arrhizus to convert progesterone into antiinflammatory and other dmgs via 11- -hydroxyprogestrone, have proved to be very successful. However, comparatively little useful information exists from public domain sources, despite (or perhaps because) a market of hundreds of millions /a exists for such microbially transformed steroids (cortisone, aldosterone, prednisolone and prednisone etc.) produced by microbial hydroxylation and dehydrogenation reactions coupled with complimentary chemical steps. 

A feature of some pterocarpan phytoalexins (e.g., pisatin and glyceollin of pea and soybean, respectively) is their hydroxylation at position 6a, a reaction catalyzed by a microsomal cytochrome P450 monooxygenase.49 50 A cDNA encoding this enzyme was recently characterized from elicited soybean cell cultures.51 The microsomal protein, expressed in yeast cells, catalyzed the stereoselective hydroxylation of (6a/ , lla/ )-3,9-dihydroxypterocarpan to its 6a-hydroxy derivative. It was also demonstrated that the enzyme expression is regulated at the transcriptional level.51... 

Epoxidation of cyclic alkenes is stereoselective, with reaction taking place on the less hindered face, or directed by hydrogen bonding to a hydroxyl group OAc OAc OH OH... 

Allylic and propargylic 3-keto sulfoxides could be reduced as well as saturated compounds. Optically active allylic 3-hydroxy sulfoxides present some specific interest because of the possible hydroxylation of the double bond leading to vicinal triols. The osmium tetroxide catalyzed hydroxylation reaction of the double bond in the presence of trimethylamine N-oxide is highly stereoselective the (/ ,/ )-3-hydroxy sulfoxide gave only one diastereoisomeric triol as a result of a cis hydroxylation of the double bond and a symbiotic effect of the two chiral centers in the asymmetric induction (the (S,/ )-isomer gave a lower de). 

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