Enhancing the scope of the Diels-Alder reaction through isonitrile chemistry: emergence of a new class of acyl-activated dienophiles

α,β-Unsaturated imides, formylated at the nitrogen atom, comprise a new and valuable family of dienophiles for servicing Diels-Alder reactions. These systems are assembled through extension of recently discovered isonitrile chemistry to the domain of α,β-unsaturated acids. Cycloadditions are facilitated by Et(2)AlCl, presumably via chelation between the two carbonyl groups of the N-formyl amide. Applications of the isonitrile/Diels-Alder logic to the IMDA reaction, as well as methodologies to modify the N-formyl amide of the resultant cycloaddition product, are described. It is expected that this easily executed chemistry will provide a significant enhancement for application of Diels-Alder reactions to many synthetic targets.     

A neurosteroid analogue photolabeling reagent labels the colchicine-binding site on tubulin: a mass spectrometric analysis

Previous studies have shown that the neurosteroid analogue, 6-Azi-pregnanolone (6-AziP), photolabels voltage-dependent anion channels and proteins of approximately 55 kDa in rat brain membranes. The present study used two-dimensional electrophoresis and nanoelectrospray ionization ion-trap mass spectrometry (nano-ESI-MS) to identify the 55 kDa proteins (isoelectric point 4.8) as isoforms of β-tubulin. This identification was confirmed by immunoblot and immunoprecipitation of photolabeled protein with anti-β-tubulin antibody and by the demonstration that 6-AziP photolabels purified bovine brain tubulin in a concentration-dependent pattern. To identify the photolabeling sites, purified bovine brain tubulin was photolabeled with 6-AziP, digested with trypsin, and analyzed by matrix-assisted laser desorption/ionization MS (MALDI). A 6-AziP adduct of TAVCDIPPR(m/z?= 1287.77), a β-tubulin specific peptide, was detected by MALDI. High-resolution liquid chromatography-MS/MS analysis identified that 6-AziP was covalently bound to cysteine 354 (Cys-354), previously identified as a colchicine-binding site. 6-AziP photolabeling was inhibited by 2-methoxyestradiol, an endogenous derivative of estradiol thought to bind to the colchicine site. Structural modeling predicted that neurosteroids could dock in this colchicine site at the interface between α- and β-tubulin with the photolabeling group of 6-AziP positioned proximate to Cys-354.     

Polyketide proofreading by an acyltransferase-like enzyme

Trans-acyltransferase polyketide synthases (trans-AT PKSs) are an important group of bacterial enzymes producing bioactive polyketides. One difference from textbook PKSs is the presence of one or more free-standing AT-like enzymes. While one homolog loads the PKS with malonyl units, the function of the second copy (AT2) was unknown. We studied the two ATs PedC and PedD involved in pederin biosynthesis in an uncultivated symbiont. PedD displayed malonyl- but not acetyltransferase activity toward various acyl carrier proteins (ACPs). In contrast, the AT2 PedC efficiently hydrolyzed acyl units bound to N-acetylcysteamine or ACP. It accepted substrates with various chain lengths and functionalizations but did not cleave malonyl-ACP. These data are consistent with the role of PedC in?PKS proofreading, suggesting a similar function for other AT2 homologs and providing strategies for?polyketide titer improvement and biosynthetic investigations.     

Curing theory of A_f-A_g type free radical polymerization (I)──Distribution function and its invariant property

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The geometry of N = 2 Maxwell-Einstein supergravity and Jordan algebras

We construct the general coupling of nN = 2 Maxwell super-multiplets to N = 2 supergravity in five spacetime dimensions. In the case that the scalar field manifold is symmetric we find a complete classification based on Jordan algebras. Apart from the generic case there are also four “exceptional” cases associated with the Jordan algebras J₃^$\text{A}$ of 3 × 3 hermitian matrices over the division algebras $\text{A}\text{=}\text{R}\text{,}\text{C}\text{,}\text{H}\text{,}\text{O}$. Similar results follow for four dimensions, by dimensional reduction.     

The gauge-invariant N=2 supersymmetric σ-model with general scalar potential

We construct the supersymmetric σ-model, in six dimensions, for an arbitrary hyper-Kähler manifold, and its minimal coupling to super-Yang-Mills theory. Non-trivial reduction to five or four dimensions yields the corresponding five- or four-dimensional N = 2 supersymmetric model with general scalar potential. We discuss briefly the coupling to supergravity in six dimensions and we give the on-shell supergravity torsion constraints.     

A novel and efficient synthesis of the naturally occurring nucleoside doridosine

1-Methylisoguanosine was synthesized by a one-pot reaction involving a condensation of 5-amino-1-(β-$\text{D}$-ribofuranosyl)imidazole-4-carboxamide (1) with methyl isothiocyanate, treatment of the resulting thiourea derivative with DCC furnished 5-(3-methyl-1-ureido)-1-(β-$\text{D}$-ribofuranosyl)imidazole-4-carbonitrile (4) which was then annulated with ethanolic ammonia to furnish doridosine in a 68% yield from 1.     

Production of 3H at large momentum in alpha-12C collisions at 2A GeV

Calculations of the longitudinal and transverse momentum distributions for 3H production at large momentum in alpha-12C collisions near 2 A GeV are compared to experiment. Triton exchange and final-state interactions are shown to represent large corrections to the impulse approximation for proton knockout. A method for calculating interference effects for inelastic fragmentation is discussed. Good agreement with experiment is found using a phenomenological overlap function for 3H-p successful in describing 3H production in pion-induced reactions. Comparisons to momentum distributions obtained through (p, 2p) and (e, ep) reactions on 4He are made.