Synthesis of High-Value 1,6-Enynes by Tandem Fragmentation/Olefination

A tandem process provides high-value 1,6-enynes that are otherwise difficult to prepare. Two base-mediated reactionsfragmentation and olefinationare executed in a coordinated manner that is overall more efficient than either reaction on its own. The 1,6-enynes can be strategically employed in conjunction with carbocyclization to deliver important targets, as noted for reported syntheses of hirsutene and illudol

Reaction Discovery Using Neopentylene-Tethered Coupling Partners: Cycloisomerization/Oxidation of Electron-Deficient Dienynes

A rhodium-catalyzed cycloisomerization and oxidation of tethered dienynes for the synthesis of indanes is described. An auxiliary fragmentation/olefination method (also described herein) provides novel access to tethered alkyne-dienoate substrates. The reported method circumvents current limitations in and expands the scope of inverse-demand Diels–Alder-type cycloadditions. Traditional discovery substrates involving malonate-, ether-, and sulfonamide-based tethers are problematic in the current methodology, underscoring the unique virtue of neopentylene-tethered substrates for reaction discovery

Six-Step Synthesis of Alcyopterosin A, a Bioactive Illudalane Sesquiterpene with a <i>gem</i>-Dimethyl­cyclopentane Ring

Strategic pairing of ring openings and cycloisomerization provides rapid and efficient “open and shut” entry into sparsely functionalized illudalanes, as exemplified here in the context of a six-step synthesis of alcyopterosin A. Key steps include a tandem ring-opening fragmentation/olefination process for preparing a neopentyl-tethered 1,6-enyne, ring-opening olefination telescoped with alkyne homologation, and Rh-catalyzed oxidative cycloisomerization

Analysis of protease, hemolysin, lipase, and rhamnolipid production by <i>P. aeruginosa fadD</i> mutants.

<p>The <i>fadD2</i> mutant displayed significantly decreased production of proteases (A), hemolysins (B), lipases (C), and rhamnolipids (D), while no growth defects in LB were observed (E). These assays were conducted in triplicate and are expressed as a percentage of the mean value of the wildtype PAO1 ± s.e.m.</p

Complementation of the <i>E. coli fadD</i> mutant with <i>P. aeruginosa fadD</i> homologues.

a<p>(-) denotes no growth on a patch; (+) denotes growth: (+1) is very little growth and (+6) is heavy growth after 3 days.</p

Altered swimming and swarming motility of <i>P. aeruginosa fadD</i> mutants.

<p>(A) Swimming motility of <i>fadD</i> mutants and their complements. (B) Swarming migration of <i>fadD</i> mutants and their complements. These figures are representative of multiple experiments. Strain designation is the same as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013557#pone-0013557-t003" target="_blank">Table 3</a>: wildtype PAO1, P007; <i>fadD1</i>^-, P175; <i>fadD2</i>^-, P547; Δ<i>fadD2D1</i>, P177; <i>fadD1</i>^- complement, P541; <i>fadD2</i>^- complement, P549; and Δ<i>fadD2D1</i> complement, P543.</p

Kinetic properties of FadD1 and FadD2 with various substrates.

a<p>Kinetic constants (V_max and <i>K_m</i>) determined using Hanes-Woolf plot.</p>b<p>nmole of acyl-CoA formed/min/mg of protein.</p>c<p>s^-1; determined using MW of FadD1 (61,655) and FadD2 (61,373).</p>d<p>mM of ATP or FA.</p>e<p>mM^-1 s^-1; represents enzyme catalytic efficiency.</p

Primers used in this study.

a<p>Restriction enzyme sites utilized in this study are underlined.</p>b<p>Primers synthesized RNase free and HPLC purified.</p

Plasmids used in this study^a.

a<p>For plasmids constructed in this study, please see text for further details.</p>b<p>Please use lab ID for requesting plasmids.</p

Growth analysis of <i>fadD</i> mutants using various FAs as sole carbon sources.

<p>Although <i>fadD</i> mutants showed various defects when grown with FAs of different chain-lengths (see top of graphs in B-I), no growth defects were observed for any of the mutants when grown with casamino acids (CAA) as a control (A). All three <i>P. aeruginosa</i> mutants were fully complemented by the respective missing gene(s) and grew as well as the wildtype PAO1 on all carbon sources. Not shown are the three control mutant strains (PAO1-<i>fadD1</i>::<i>FRT</i>/<i>attB</i>::miniCTX2, PAO1-<i>fadD2</i>::<i>FRT</i>/<i>attB</i>::miniCTX2, and PAO1-Δ<i>fadD2D1</i>::<i>FRT</i>/<i>attB</i>::miniCTX2) having the empty miniCTX2 integrated into their chromosomes, where all had similar growth characteristics to the non-complemented mutants.</p