Showing papers by "Laurence E. Burgess published in 1999"
TL;DR: A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines, which demonstrated a remarkable distanced-defined structure-activity relationship against human tryptase with one series possessing subnanomolar potencies.
Abstract: Human lung tryptase, a homotetrameric serine protease unique to mast cell secretory granules, has been implicated in the pathogenesis of asthma. A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines. These compounds demonstrated a remarkable distanced-defined structure–activity relationship against human tryptase with one series possessing subnanomolar potencies. Additional evidence supporting the concept of active-site bridging is also presented.
63 citations
TL;DR: In this article, an asymmetric synthesis of 25, which constitutes the C(3)−C(21) segment of the stereochemically complex ansa chain of herbimycin A (2) has been achieved.
15 citations
TL;DR: In this paper, an asymmetric synthesis of 25, which constitutes the C(3)−C(21) segment of the stereochemically complex ansa chain of herbimycin A (2) has been achieved.
Abstract: The asymmetric synthesis of 25, which constitutes the C(3)–C(21) segment of the stereochemically complex ansa chain of herbimycin A (2) has been achieved. The approach features the furan-hydropyran transformations 7→5 and 8→6 and the fragment coupling of 5 and 6 to produce the trisubstituted alkene 4 with high stereoselectivity. Stereoselective addition of the aryl anion derived from 24, which possesses the novel BIPSOP protecting group for the primary amine function, to the lactol 22 then delivered 25 as the major product.