K. B. Sharpless

Stereo and regioselective openings of chiral 2,3-epoxy alcohols. Versatile routes to optically pure natural products and drugs. Unusual kinetic resolutions

A diverse selection of new synthetic applications of the titaniumcatalyzed asymmetric epoxidation (AE) process is described. These include asymmetric syntheses of (+)_DarvonR Alcohol, (-)-bestatin, (+)-2-methyl bestatin, (-)-propranolol, (-)-u-amino--hydroxybutyric acid, and (_) and (+)_frontalin. The kinetic resolution mode of the AE process was used to prepare chiral insect pheromones in very high (>99% e.e.) optical purity; these include (+)-and (-)-ct-caprolactone, (-)-exobrevicomin, (-)-endobrevicomin, (+)_and (-)-ipsdienol, and (+)-trans-verbenol. A number of unusual kinetic resolutions based on the AE process are presented; these include resolutions of allenic alcohols, n-acetylenic carbinols, -hydroxy sulfides, and a dienol. Almost two years ago we first reported on the titanium-catalyzed asymmetric epoxidation process shown in Scheme 11a In the interim this new chiral catalyst system has rapidly become accepted as one of the best means for synthesizing a great variety of optically pure

Stereoselective epoxidation of acyclic allylic alcohols. A correction of our previous work.

A reinvestigation of the stereoselectivities for the epoxidation of acyclic allylic alcohols with MCPBA, and with tert-butyl hydroperoxide catalyzed by V+5 and Mo+6 revealed a number of errors in our original work1 which are rectified. Optimum O-C-C=C dihedral angles are proposed.

Some aspects of substrate specificity in biological demethylation at C4 of steroids

Abstract In order to ascertain some of the structural requirements for substrate activity in the oxidative demethylation at C4 of steroids by rat liver enzymes, several steroids have been synthesized, labeled with tritium, and incubated with rat liver enzyme preparations. These include 4α-formyl-4β-methylcholestan-3β-ol ( 4 ), 4-methylcholest-3-ene ( 14 ), 3β,4β-epoxy-4α-methylcholestane ( 20 ), 3α,4α-epoxy-4β-methylcholestane ( 18 ), 4α-ethyl-4β-methylcholestan-3β-ol ( 21 ), and 4β-ethyl-4α-methylcholestan-3β-ol ( 22 ). Enzymic incubation demethylates 4 with an efficiency consistent with its being an intermediate in the biological demethylation of 4,4-dimethyl sterols, but all of the other substrates are recovered unchanged.

Enzymic transformation of an acyclic sesterterpene terminal epoxide into a lanosterol analogue

SUBSEQUENT to the finding that squalene 2,3-oxide is a general intermediate in the enzymic conversion of squalene into lanosterol and other 3-hydroxylated sterols, the transformation of structurally modified squalene oxides into sterol-like products was first reported from these laboratories. In that preliminary study, the effect on side-chain reduction and shortening was tested and found not to deter seriously the biological cyclization process. In extending this approach, we have now determined that the absence of an entire isoprenoid unit from the non-oxidized terminus of squalene oxide does not prevent normal biochemical cyclization : constant. Another portion of the crude sterol product was silylated with trimethylsilyl chloride in pyridine and subjected to fractionation by preparative g.1.c. (5% diethyleneglycol succinate a t 190), 47% of the radioactivity appearing in a single peak having the same retention time (Rcholestane 0.71) as the trimethylsilyl ether of authentic (11). The radioactive silyl ether was collected, hydrolysed with ethanolic KOH, and subjected to preparative g.1.c. on an XE-60 column at 180; 91% of the activity was found in a fraction with the same retention time (Rcholestane 1-90) as authentic (11).