Eldon G. Nidy

Taxol chemistry. 7-O-triflates as precursors to olefins and cyclopropanes

Abstract 7-O-Triflates of baccatin III or of taxol analogs are convenient precursors in alternate syntheses of Δ 6,7 -taxols and 7β,8β-methano (cyclopropyl) taxols, two of the products initially obtained from reaction of taxols with methylDAST; hydrazine is an effective reagent for conversion of the 10-acetate group to the hydroxyl group.

Synthesis of the four isomers of 5-hydroxy-PGI1

We wish to report here the syntheses of (5S, 6R)-5-hydroxy-, (5R, 6R)-5-hydroxy-, (5R, 6S)-5-hydroxy-, and (5S, 6S)-5-hydroxy-PGI1 and their methyl ester derivatives. Treatment of (5R, 6S)-epoxy- and (5S, 6R)-epoxy-PGF1alpha methyl esters with acid washed silica gel afforded (5R, 6R)-5-hydroxy- and (5S, 6S)-5-hydroxy-PGI1 methyl esters; correspondingly, silica promoted cyclization of (5S, 6S)-epoxy- and (5R, 6R)-epoxy-PGF1alpha methyl esters yielded (5S, 6R)-5-hydroxy- and (5R, 6S)-5-hydroxy-PGI1 methyl esters. Alternatively, the 5-hydroxyl group was introduced into the PGI1 skeleton via reaction of the 5-mercuric halides with sodium borohydride in the presence of oxygen. Stereochemical assignments were based on their mode of synthesis and 1H nmr shift differences.

Asymmetric synthesis of the diastereoisomers of the leukotriene B4 antagonist, U-75302

Abstract A synthesis of the four diastereoisomers of U-75302 has been completed using ( R ) and ( S )-glycidol as the precursors to the C5 chiral centers and asymmetric reductions of a ketone to generate the C12 centers.

An asymmetric synthesis of (R) and (S)-1-alkoxy-2,3-propanediols including precursors to platelet activating factor

The titanium-assisted nucleophilic opening of glycidol with primary aliphatic alcohols gives 1-alkoxy-2,3-propanediols. The titanium alkoxide used in the reaction should be the alkoxide of the alcohol used for the reaction. When optically active (S)-glycidol is used in the reaction, (S)-1-alkoxy-2,3-propanediols are obtained without loss of optical activity. When the reaction is carried out at 70-75 degrees C without solvent, the 1-alkoxy-2,3-propanediols are obtained in yields of 45-59%. The regioisomeric 2-alkoxy-1,3-propanediols are found to the extent of 4-6% in the reaction. The optical purity of glycidol can be measured from the high field (500 MHz) nuclear magnetic resonance spectrum of the Mosher ester.