Synthesis of streptolydigin, a potent bacterial RNA polymerase inhibitor

Streptolydigin is a highly potent, broad-spectrum antibiotic produced by Streptomyces lydicus, which inhibits bacterial RNA polymerase. We describe the first synthesis of streptolydigin, which was assembled in a highly convergent and fully stereocontrolled fashion with a longest linear sequence of 24 steps starting from commercially available precursors. The assembly process entailed preparation of fully elaborated streptolic and ydiginic subunits of the natural product, followed by a highly efficient union in a three-step one-pot procedure, which included Dieckmann cyclization with a concomitant imide opening, Horner-Wadsworth-Emmons olefination, and desilylation.     

Memory-efficient algorithm for lens distortion compensation

Distortion introduced by a lens in a measurement system based on an image sensor usually must be compensated. The memory used for distortion compensation by a lookup table is proportional to the image sensor size. To reduce the memory usage, a compression algorithm is proposed and implemented.     

Structure of bistramide A-actin complex at a 1.35 angstroms resolution

Bistramide A is a highly potent antiproliferative marine natural product from Lissoclinum bistratum. We have previously established actin as the primary cellular receptor of bistramide A. We report herein the X-ray structure of bistramide A bound to monomeric actin at a resolution of 1.35 A. The most notable aspect of the bistramide A-actin structure is an extensive hydrogen-bonding network established upon a deep penetration of the central segment of bistramide A into the actin-binding cleft between subdomains 1 and 3. The structure presents the first insight into the observed ability of bistramide A to modulate G-actin polymerization. The structural information combined with our ability to chemically modify the bistramide framework provides the basis for rational development of a series of new synthetic analogues as useful probes for studying actin cytoskeleton and as potential therapeutic leads.     

Synthesis of (-)-pinolidoxin: divergent synthetic strategy exploiting a common silacyclic precursor

[reaction: see text] We describe a highly convergent and efficient synthesis of (-)-pinolidoxin, a potent modulator of plant pathogenesis, providing unambiguous determination of the relative and absolute stereostructure of this highly oxygenated fungal metabolite. Our unique strategy highlights the applications of novel silacyclic precursors for stereocontrolled polyol synthesis and features the finding of the reversible ring-closing metathesis.     

Racemic and asymmetric Diels-Alder reactions of 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes

Achiral and chiral 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes were prepared from readily available starting materials. Although more stable than the parent 1-amino-3-siloxy dienes, the 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes are still very reactive in Diels-Alder reactions, somewhat more than 1,3-dialkoxy-1, 3-butadienes (e.g., Danishefsky's diene). The cycloadditions of the achiral and chiral dienes with several different dienophiles were examined. The reactions proceeded in good yield, with modest to high endo selectivity. The chiral dienes exhibited excellent facial selectivity in cycloadditions with alpha-substituted acroleins, maleic anhydride and N-phenylmaleimide. Upon reduction and hydrolysis of the cycloadducts, substituted cyclohexenones were obtained with ee's ranging from 22% to >98%.