Michael L. Edwards

A new route to vinyl fluorides

The carbanion of diethyl 1-fluoro-1-(phenylsulfonyl)methanephosphonate (7), generated in situ from fluoromethyl phenyl sulfone (3) undergoes the Horner-Wittig reaction with aldehydes and ketones to yield α-fluoro-α,β-unsaturated sulfones (8). Reductive removal of the phenylsulfonyl group provides a facile two-step route to vinyl fluorides froa 3, where the fluorine source is either KF or DAST.

Stereospecific synthesis of secondary amines by the Mitsunobu reaction

Abstract A facile synthesis of secondary amines from alcohols is reported with N-methyltri-fluoromethanesulfonamide ( 2 ) in the Mitsunobu reaction. The reaction was demonstrated to proceed with inversion of configuration and provided a convenient synthetic route to the (R,R) and (S,S)-enantiomers ( 24 and 25 ) of the antitumor polyamine 1 by utilizing either (R)- or (S)-3-(N-methyltrifluoromethanesulfonamido)butan-1-ol ( 21 or 22 ) and 1,7-bis-(trifluoromethanesulfonamido)heptane ( 33 ). Reagents 21 and 22 were prepared from commercially available (S)- and (R)-1,3-butanediol, respectively.

Synthesis and DNA-binding properties of polyamine analogues

The synthesis of a series of novel polyamine analogues is reported. The DNA binding of these compounds and a variety of other polyamines were compared with their IC50 values against HeLa cell. There seemed to be no apparent correlation between the DNA binding and toxicity against HeLa cells.

Difluoromethyldiphenylphosphine oxide. A new reagent for conversion of carbonyl compounds to 1,1-difluoroolefins.

Abstract Difluoromethyldiphenylphosphine oxide ( 5 ) was synthesized from chlorodifluoromethane and diphenylphosphine oxide. Reaction of 5 with a variety of ketones and aldehydes gave 1,1-difluoroolefins. Monofluoromethyldiphenylphosphine oxide ( 7 ) was also synthesized but did not give monofluoroolefins.

Effects of polyamine analogs on the extent and fidelity of in vitro polypeptide synthesis

A series of polyamine analogs has been examined for their ability to support protein synthesis in an in vitro rabbit reticulocyte translation system. Diamines were found to stimulate protein synthesis to the greatest extent (8-12 fold). Triamines, tetraamines and pentaamines only stimulated 2-4 fold under these conditions although much lower concentrations were required. At elevated temperatures (45 degrees C), diamines were somewhat more active than at lower temperature but activity of longer chain polyamines was elevated very significantly. Polyamines with terminal benzyl or smaller alkyl groups had diminished activity. It is concluded that both charge and charge distribution determine the ability of polyamines to stimulate translation. Fidelity studies identified two classes of polyamines: those which are able to lower the optimal Mg2+ concentration required for amino acid misincorporation while not affecting extent of misincorporation relative to Mg2+ alone, and those which are sparing for Mg2+ and also stimulate extent of misincorporation.

Use of the Mitsunobu reaction in the synthesis of polyamines

Abstract The Mitsunobu reaction has been used in the synthesis of polyamine analogues. The synthesis of the (R,R), (S,S) and meso- isomers of a tetraamine are described. The chemistry was used to synthesize a fluorinated polyamine analog and a hexaamine.

(E) and (Z)5′-fluoro olefin carbocyclic nucleosides: effect of olefin geometry on inhibition of s-adenosyl-l-homocysteine hydrolase

Abstract (E) and (Z) 4′,5′-Didehydro-5′-deoxy-5′-fluoroaristeromycin ( 9a and 9b ) were synthesized utilizing the fluoro-Pummerer reaction . Fluoro olefin 9a was a time-dependent inhibitor of S-adenosyl-L- homocysteine hydrolase whereas 9b was a competitive inhibitor. The effects of 9a and 9b on T cell proliferation are presented.

Antioxidant and cholesterol lowering properties of 2,6-DI-t-butyl-4-[(dimethylphenylsilyl)methyloxy]phenol and derivatives: A new class of anti-atherogenic compounds

Abstract Di- t -butylphenol derivatives were synthesized and evaluated as antioxidants and cholesterol lowering agents. When evaluated in cholesterol-fed rabbits, the compounds were found to exhibit both properties. Of special interest was the finding that several of the compounds elevated HDL cholesterol levels.