Gregory P. Roth

Catalyst tailoring for palladium-mediated cross coupling of arylstannanes with vinyl triflates

Abstract Vinyl triflates couple smoothly with a variety of arylstannanes provided a polar, aprotic solvent is used in conjunction with a “ligandless” palladium catalyst, or catalytic system involving weak ligands such as triphenylarsine. Commonly employed ligands, for example, triphenylphosphine, were found to strongly inhibit the coupling.

Discovery of small molecule benzimidazole antagonists of the chemokine receptor CXCR3

High-throughput screening identified a low molecular weight antagonist of CXCR3 displaying micromolar activity in a membrane filtration-binding assay. Systematic modification of the benzimidazole core and tethered acetophenone moiety established tractable SAR of analogs with improved physicochemical properties and sub-micromolar activity across both human and murine receptors.

Taxol® structure-activity relationships: synthesis and biological evaluation of taxol analogs modified at C-7

Abstract A series of taxol derivatives, modified at C-7, is described. This includes sulfonate, silylether, ester, carbonate, carbamate, fluoro, dehydro and deoxy derivatives. Biological evaluation shows that these modifications do not usually significantly compromise activity. However, none of the C-7 analogs prepared thus far have been shown to be better than taxol in both in vitro and in vivo assays.

Trimethylsilylfluorosulfonate (TMSOFs): An alternative to TMS triflate as a source of Me3Si+

Abstract Generation of trimethylsilylfluorosulfonate in situ provides a useful source of TMS+, the reactivity of which in essentially equivalent to that of TMS triflate. Its precursors, in particular FSO3H, are less costly than those of TMSOTf or the reagent itself

Palladium in cephalosporin chemistry: an inexpensive triflate replacement for palladium acetate mediated coupling reactions

Abstract 3-Fluorosulfonyloxy-3-cephems are easily prepared and subsequent palladium(0) catalyzed coupling with various vinylstannanes proceeds in excellent yields with stereospecific transfer of the alkene fragment.

Alkoxycarbonylation Reactions Using Aryl Fluorosulfonates

Abstract Aryl fluorosulfonates are shown to undergo palladium catalysed alkoxycarbonylation with a variety of alcohols under mild basic conditions at ambient CO pressure.

Palladium in Cephalosporin Chemistry: Mild Triflate Couplings in the Absence of Phosphines and Halide Donors

Abstract Palladium catalyzed triflate-organostannane couplings are shown to proceed in a very mild manner in the absence of added phosphine and halide reagents. This protocol has been demonstrated for 3-trifloxycephems and vinyl triflates.

Lead identification of 2-iminobenzimidazole antagonists of the chemokine receptor CXCR3.

Modification of a 2-iminobenzimidazole series derived from an HTS hit resulted in compounds with improved in-vitro species selectivity. Incorporation of an 8-quinoline amide and conformational rigidification of an aliphatic tether furnished potent compounds suitable for further lead optimization.

Reaction of paclitaxel and 10-desacetyl baccatin III with diethylamino sulfurtrifluoride

Abstract Reaction of protected paclitaxel with diethylamino sulfurtrifluoride (DAST), to furnish the 7-fluoro paclitaxel, gives a mixture of four products, two of which have not been previously reported. The product distribution is shown to be solvent dependent. An efficient process for the preparation of the parent 7-α-fluoro baccatin III from 10-desacetyl baccatin III is also described.

An interesting c-ring contraction in paclitaxel (Taxol®)

Abstract An interesting pinacol rearrangement involving 7-epi-6α-tosylate/triflate-paclitaxel derivatives ( 6 ) and ( 10 ), with the formation of five-membered C-ring containing analogs ( 7 ) and ( 11 ), is described.