N-phenylselenophthalimide (NPSP) : A valuable selenenylating agent

The phenylseleno group (PhSe) has evolved in recent years as a very useful and versatile functionality. Its facile introduction into organic molecules and its subsequent oxidative or reductive removal, has allowed many important synthetic transformations.^1–7 Due to the fact that, similarly to halogens, it can exist either as an electrophilic species (PhSe⁺) or as a nucleophilic one (PhSe^-), this group can be introduced either via nucleophilic substrates (e.g. carbanions, olefins), or via electrophilic ones (e.g. epoxides, halides), as illustrated in Scheme 1. Another valuable aspect of the phenylseleno group is that it can be readily oxidized to the corresponding selenoxide(PhSe(O)—), which undergoes β-hydrogen abstraction and syn-elimination to form olefins, under relatively mild conditions (Scheme 2(a)). Furthermore, this group can be substituted with hydrogen, upon the action of an appropriate reducing agent (Scheme 2(b)).The great synthetic utility of the phenylseleno group is apparent from its extensive utilization in numerous natural products syntheses,¹ as well as many other synthetic studies.^2–7     

Novel proresolving aspirin-triggered DHA pathway

Endogenous mechanisms in the resolution of acute inflammation are of interest because excessive inflammation underlies many pathologic abnormalities. We report an aspirin-triggered DHA metabolome that biosynthesizes a potent product in inflammatory exudates and human leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 [AT-(NPD1/PD1)]. The complete stereochemistry of AT-(NPD1/PD1) proved to be 10R,17R-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. The chirality of hydroxyl groups and geometry of the conjugated triene system essential for bioactivity were established by matching biological materials with stereochemically pure isomers prepared by organic synthesis. AT-(NPD1/PD1) reduced neutrophil (PMN) recruitment in murine peritonitis in a dose-dependent fashion whereby neither a Δ(15)-trans-isomer nor DHA was effective. With human cells, AT-(NPD1/PD1) decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. These results indicate that AT-(NPD1/PD1) is a potent anti-inflammatory proresolving molecule.     

Stability of a microwave heated fluid Layer

When a time harmonic electromagnetic wave impinges on a slaba certain portion of the wave creates heat within the slab throughdipolar and ohmic heating. The electrical and thermal propertiesof the material dictate the dynamical nature of the heatingprocess, as well as the steady-state temperature profile. Thematerial considered here is a slab of fluid. We consider thecase where the fluid is bounded by thin rigid layers of transparentmaterial. The steady-state heating profile governs the typesof convective motions that can occur and also affects the stabilitycharacteristics of temperature, pressure and velocity perturbationsintroduced in the slab. The main objective here is to examinesuch stability characteristics, initially in the linear regime.Both rigid-rigid and rigid-free configurations are considered.     

Stereocontrolled total synthesis of neuroprotectin D1 / protectin D1 and its aspirin-triggered stereoisomer

Neuroprotectin D1 / protectin D1, a potent anti-inflammatory, proresolving, and neuroprotective lipid mediator derived biosynthetically from docosahexaenoic acid, was prepared in enantiomerically pure form via total organic synthesis. The synthetic strategy is highly stereocontrolled and convergent, featuring epoxide opening of glycidol starting materials for the introduction of the 10(R) and 17(S) hydroxyl groups. The desired alkene Z geometry was secured via the cis-reduction of alkyne precursors, while the conjugated E,E,Z triene was introduced at the end, in order to minimize Z/E isomerization. The same strategy, was also employed for the total synthesis of aspirin-triggered neuroprotectin D1 / protectin D1 having the 17(R)-stereochemistry. Synthetic compounds obtained with the reported method were matched with endogenously derived materials, and helped establish their complete stereochemistry.     

Formation of eight-membered ring β-keto lactones via the intramolecular trapping of hydroxy acylketenes

Eight-membered ring β-keto lactones were prepared from 2,2,6-trimethyl-4H-1,3-dioxin-4-one in three steps involving conjugate addition to α,β-unsaturated aldehydes or ketones, followed by conversion to an alcohol and thermolysis. The formation of these eight-membered rings involves the intramolecular trapping of a hydroxy acyl ketene intermediate and is facilitated by a suppressed ring strain and an unfavorable intramolecular hydrogen bond, which is suggested to favor the formation of oligomers. These aspects of the reaction were supported by molecular mechanics calculations.     

Stereoselective synthesis of anti-alpha-(difluoromethyl)-beta-amino alcohols by boronic acid based three-component condensation. Stereoselective preparation of (2S,3R)-difluorothreonine

Starting from optically active 3,3-difluorolactaldehyde, an alkenyl or aryl boronic acid, and an amine, a one-step three-component methodology was developed for the stereoselective preparation of anti-alpha-(difluoromethyl)-beta-amino alcohols. beta-Furyl-substituted anti-alpha-(difluoromethyl)-beta-amino alcohol was further elaborated to form (2S,3R)-difluorothreonine in high yield and ee.     

Lipoxins and Related Eicosanoids: Biosynthesis,Biological Properties,and Chemical Synthesis

Among the various enzymes found in human tissues that act on arachidonic acid, there are three major types of lipoxygenases (LO), operating at the 5-, 12-, and 15-positions. The 5-LO is a key enzyme and plays a central role in the biosynthesis of leukotrienes, which are potent arachidonate-derived mediators of allergy and inflammation. Because of the importance of the 5-LO-derived products in human pathophysiology, studies were initiated to examine the consequences of initial lipoxygenation at C15 of arachidonic acid as well as to probe interactions between the major LO pathways. These studies led to the identification of a new series of biologically active tetraene-containing eicosanoids termed lipoxins. This article summarizes the isolation, biosynthesis, and chemical synthesis of lipoxins and related systems, and reviews recent results concerning their formation and biological activities. The total synthesis of these molecules based on a new and general synthetic strategy involving palladium catalysis is reviewed. This synthetic approach has allowed the preparation of several types of acyclic eicosanoids in their naturally occurring forms which, in turn, allowed comparisons with naturally derived materials and enabled detailed studies of the biological actions of these biomolecules. Structure–activity relationships were also derived by combining chemical synthesis and biological investigations.     

Spectroscopic characterization and assignment of reduction potentials in the tetraheme cytochrome C554 from Nitrosomonas europaea

The tetraheme cytochrome c(554) (cyt c(554)) from Nitrosomonas europaea is an essential electron transfer component in the biological oxidation of ammonia. The protein contains one 5-coordinate heme and three bis-His coordinated hemes in a 3D arrangement common to a newly characterized class of multiheme proteins. The ligand binding, electrochemical properties, and heme-heme interactions are investigated with M?ssbauer and X- and Q-band (parallel/perpendicular mode) EPR spectroscopy. The results indicate that the 5-coordinate heme will not bind the common heme ligands, CN(-), F(-), CO, and NO in a wide pH range. Thus, cyt c(554) functions only in electron transfer. Analysis of a series of electrochemically poised and chemically reduced samples allows assignment of reduction potentials for heme 1 through 4 of +47, +47, -147, and -276 mV, respectively. The spectroscopic results indicate that the hemes are weakly exchange-coupled (J approximately -0.5 cm(-)(1)) in two separate pairs and in accordance with the structure: hemes 2/4 (high-spin/low-spin), hemes 1/3 (low-spin/low-spin). There is no evidence of exchange coupling between the pairs. A comparison of the reduction potentials between homologous hemes of cyt c(554) and other members of this new class of multiheme proteins is discussed. Heme 1 has a unique axial N(delta)-His coordination which contributes to a higher potential relative to the homologous hemes of hydroxylamine oxidoreductase (HAO) and the split-Soret cytochrome. Heme 2 is 300 mV more positive than heme 4 of HAO, which is attributed to hydroxide coordination to heme 4 of HAO.