Sequential hydrocarbon functionalization: allylic C-H oxidation/vinylic C-H arylation

A Pd(II)/sulfoxide-catalyzed sequential allylic C-H oxidation/vinylic C-H arylation of alpha-olefins to furnish E-arylated allylic esters in high regio- and E:Z selectivities (>20:1) is reported. The broad scope of this method with respect to the alpha-olefin, carboxylic acid, and aryl boronic acid enables the rapid assembly of densely functionalized fragments for complex molecule synthesis from cheap, abundant hydrocarbon starting materials. The Pd(II)/sulfoxide-catalyzed vinylic C-H arylation of electronically unbiased olefins with aryl boronic acids proceeds under oxidative, acidic conditions and mild temperatures (room temperature to 45 degrees C).     

Asymptotics of Karhunen-Loeve Eigenvalues and Tight Constants for Probability Distributions of Passive Scalar Transport

In this paper we study the asymptotics of the probability distribution function for a certain model of freely decaying passive scalar transport. In particular we prove rigorous large n, or semiclassical, asymptotics for the eigenvalues of the covariance of a fractional Brownian motion. Using these asymptotics, along with some standard large deviations results, we are able to derive tight asymptotics for the rate of decay of the tails of the probability density for a generalization of the Majda model of scalar intermittency originally due to Vanden Eijnden. We are also able to derive asymptotically tight estimates for the closely related problem of small L₂ ball probabilities for a fractional Brownian motion.     

Synthesis and partial biological evaluation of a small library of differentially-linked beta-C-disaccharides

The synthesis of a small library of differentially-linked beta-C-disaccharides has been carried out through the use of a radical allylation-RCM strategy. Acids 6 were prepared by Keck allylation of a suitable carbohydrate-based radical precursor, followed by oxidative cleavage of the formed alkene. Dehydrative coupling of these acids with the known olefin alcohol 5 then gave the precursor esters 7 in excellent yield. Methylenation of the esters 7 was followed by RCM and in situ hydroboration-oxidation of the formed glycals to furnish the protected beta-C-disaccharides 10 in good overall yield. Five examples were then deprotected and screened for their efficacy as enzyme inhibitors of beta-glycosidase and against several solid-tumor cell lines for in vitro differential cytotoxicity.     

Review: Veratrum californicum Alkaloids

Veratrum spp. grow throughout the world and are especially prevalent in high mountain meadows of North America. All parts of Veratrum plants have been used for the treatment of ailments including injuries, hypertension, and rheumatic pain since as far back as the 1600s. Of the 17–45 Veratrum spp., Veratrum californicum alkaloids have been proven to possess favorable medicinal properties associated with inhibition of hedgehog (Hh) pathway signaling. Aberrant Hh signaling leads to proliferation of over 20 cancers, including basal cell carcinoma, prostate and colon among others. Six of the most well-studied V. californicum alkaloids are cyclopamine (1), veratramine (2), isorubijervine (3), muldamine (4), cycloposine (5), and veratrosine (6). Recent inspection of the ethanolic extract from V. californicum root and rhizome via liquid chromatography–mass spectrometry has detected up to five additional alkaloids that are proposed to be verazine (7), etioline (8), tetrahydrojervine (9), dihydrojervine (10), 22-keto-26-aminocholesterol (11). For each alkaloid identified or proposed in V. californicum, this review surveys literature precedents for extraction methods, isolation, identification, characterization and bioactivity to guide natural product drug discovery associated with this medicinal plant.     

OvoAMtht from Methyloversatilis thermotolerans ovothiol biosynthesis is a bifunction enzyme: thiol oxygenase and sulfoxide synthase activities

Mononuclear non-heme iron enzymes are a large class of enzymes catalyzing a wide-range of reactions. In this work, we report that a non-heme iron enzyme in Methyloversatilis thermotolerans, OvoA_Mtht, has two different activities, as a thiol oxygenase and a sulfoxide synthase. When cysteine is presented as the only substrate, OvoA_Mtht is a thiol oxygenase. In the presence of both histidine and cysteine as substrates, OvoA_Mtht catalyzes the oxidative coupling between histidine and cysteine (a sulfoxide synthase). Additionally, we demonstrate that both substrates and the active site iron''s secondary coordination shell residues exert exquisite control over the dual activities of OvoA_Mtht (sulfoxide synthase vs. thiol oxygenase activities). OvoA_Mtht is an excellent system for future detailed mechanistic investigation on how metal ligands and secondary coordination shell residues fine-tune the iron-center electronic properties to achieve different reactivities.

Modulation of OvoA_Mtht''s dual activities: sulfoxide synthase and thiol oxygenase.     

Functional and tuneable amino acid polymers prepared by RAFT polymerization

We report the application of reversible addition‐fragmentation chain transfer polymerization using a novel chain transfer agent toward the synthesis of a variety of copolymers containing proline‐derived monomeric units. This methodology enables ready access to a number of polymeric species with narrow molecular weight distributions, reliable functional unit incorporations, and high conversions. The methodology is also a facile approach to novel copolymeric species incorporating amino acids, which possess unique material properties and the potential for further organocatalytic application. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2009     

Finite field elements of high order arising from modular curves

In this paper, we recursively construct explicit elements of provably high order in finite fields. We do this using the recursive formulas developed by Elkies to describe explicit modular towers. In particular, we give two explicit constructions based on two examples of his formulas and demonstrate that the resulting elements have high order. Between the two constructions, we are able to generate high order elements in every characteristic. Despite the use of the modular recursions of Elkies, our methods are quite elementary and require no knowledge of modular curves. We compare our results to a recent result of Voloch. In order to do this, we state and prove a slightly more refined version of a special case of his result.      

Binary aspects and particle multiplicities of the fragments from natAg+340 MeV 40Ar deep inelastic collisions

Deep inelastic fragments from the reaction ^natAg+340 MeV ⁴⁰Ar have been studied in coincidence. Charged particles (10 ≦ Z ≦ 32) were detected and identified in Z by means of a ΔE?E telescope, while the complementary fragments were detected in a one-dimensional, solid-state position-sensitive detector. Both in-plane and out-of-plane correlations were measured. The results confirm the binary nature of the deep inelastic process for this reaction. From the measured energies and angles of the fragments and the atomic number of one of the fragments, it was possible to determine the total mass loss due to the de-excitation of the fragments as well as the total evaporated charge at symmetry. An iterative procedure is discussed which enables one to determine the masses and kinetic energies of the fragments before evaporation, as well as the total number of particles evaporated by each fragment. The widths of the in-plane and out-of-plane correlations agree with the results of the iterative calculations, as do evaporation calculations which are based on the charge equilibrium model. The experimental results support the charge equilibrium model and indicate that thermal equilibrium is achieved between the fragments at fixed mass asymmetry.     

Catalytic asymmetric synthesis of glutamate analogues

Utilizing our lateral metalation coupled with Jacobsen's catalytic asymmetric amino nitrile synthesis, we have demonstrated the ability to synthesize isoxazole-containing amino acid glutamate analogues in high yield and high enantiomeric excesses. Chiral centers alpha or beta at the C-5 position do not detract from diastereoselectivity of the Jacobsen-Strecker reaction. [reaction: see text]     

Influence of chiral thiols on the diastereoselective synthesis of γ-lactams from cyclic anhydrides

The synthesis of γ-lactams from both four-component and imine-anhydride reactions is reported. The synthesis of 2-phenylcyclohexanethiol is described and this compound was evaluated along with an additional seven chiral thiols. A range of selectivity and yields was observed and comparisons to established reactions are made in order to account for the observed reactivity.