The intramolecular Diels-Alder reaction: Stereocontrol through nonsynchronous bond formation?

Nonsynchronous bond formation in the transition state of the intramolecular Diels-Alder reaction is suggested to be an important determinant of the stereochemical outcome of the cyclization.     

Reductive dimerization of 1,3,4,6-tetramethyl-2-phenylpyrimidinium bistetrafluoborate

The diquaternary salt, 1,3,4,6-tetramethyl-2-phenylpyrimidinium bistetrafluoborate ( 3 ) was found to undergo reductive dimerization in the presence of zinc to afford the diquaternary salt 6.     

Enantioselective synthesis of (+)-majusculone

The first enantioselective synthesis of a chamigrane sesquiterpene, (+)-majusculone, has been completed. The quaternary center was generated asymmetrically by alkylidene carbene insertion, with retention of absolute configuration, from a diastereomerically pure ketal.     

Synthesis of symmetrical and unsymmetrical pyrazines

Opening of representative epoxides with 1,2-amino alcohols delivered the amino diols. The product amino diols were then oxidized under Swern conditions. The amino diketones so prepared were not isolated, but were condensed directly with hydroxylamine to give the substituted pyrazines.     

Preparation of the 5/5-spiroketal of the ritterazines

The enantiomerically pure 5/5-spiroketal required for the synthesis of the ritterazines has been prepared with high diastereocontrol by ring closure followed by equilibration.     

Curing of monomer composites, 2. The use of NMR to monitor real time curing dynamics

A novel method is described for monitoring the real‐time curing dynamics of composite monomers, exploiting site specific information provided by high resolution NMR. Important temporal information is encoded in the component lineshapes and intensities of ¹H and ¹³C NMR spectra recorded as a function of curing time. A computed simulation based on a (Q‐e)‐multicomponent kinetic model matches experimental data well, which lends confidence to the model when used in a predictive mode.     

Preclinical Evaluation of Cetuximab and Benzoporphyrin Derivative-Mediated Intraperitoneal Photodynamic Therapy in a Canine Model

Peritoneal carcinomatosis (PC) can occur as an advanced consequence of multiple primary malignancies. Surgical resection, radiation or systemic interventions alone have proven inadequate for this aggressive cancer presentation, since PC still has a poor survival profile. Photodynamic therapy (PDT), in which photosensitive drugs are exposed to light to generate cytotoxic reactive oxygen species, may be an ideal treatment for PC because of its ability to deliver treatment to a depth appropriate for peritoneal surface tumors. Additionally, epidermal growth factor receptor (EGFR) signaling plays a variety of roles in cancer progression and survival as well as PDT-mediated cytotoxicity, so EGFR inhibitors may be valuable in enhancing the therapeutic index of intraperitoneal PDT. This study examines escalating doses of benzoporphyrin derivative (BPD)-mediated intraperitoneal PDT combined with the EGFR-inhibitor cetuximab in a canine model. In the presence or absence of small bowel resection (SBR) and cetuximab, we observed a tolerable safety and toxicity profile related to the light dose received. Additionally, our findings that BPD levels are higher in the small bowel compared with other anatomical regions, and that the risk of anastomotic failure decreases at lower light doses will help to inform the design of similar PC treatments in humans.     

Structure-based discovery of glycolipids for CD1d-mediated NKT cell activation: tuning the adjuvant versus immunosuppression activity

Introduction of an aromatic group into the fatty acyl chain of alpha-GalCer modulates the activity and selectivity of IFN-gamma/IL-4 secretion through CD1d-mediated activation of NKT cells. Compound 14-16 are more potent than alpha-Galcer and biased for IFN-gamma than for IL-4. These new glycolipids may find use as adjuvants or as antimetastatic agents.     

Ocean heat content and Earthʼs radiation imbalance. II. Relation to climate shifts

In an earlier study of ocean heat content (OHC) we showed that Earth?s empirically implied radiation imbalance has undergone abrupt changes. Other studies have identified additional such climate shifts since 1950. The shifts can be correlated with features in recently updated OHC data. The implied radiation imbalance may possibly alternate in sign at dates close to the climate shifts. The most recent shifts occurred during 2001–2002 and 2008–2009. The implied radiation imbalance between these dates, in the direction of ocean heat loss, was −0.03±0.06 W/m²$-0.03\pm 0.06\text{W}/{\text{m}}^2$, with a possible systematic error of [−0.00,+0.09] W/m²$[-0.00,+0.09]\text{W}/{\text{m}}^2$.     

1-Bromo-3,3-bis(2-bromoethyl)alkanes: Precursors to 4-Substituted Quinuclidines and 1-Phosphabicyclo[2.2.2]octanes

1-Bromo-3,3-bis(2-bromoethyl)octane has been synthesized from tetrahydro-4H-pyran-4-one in 6 steps and 18% overall yield. This method is more convenient, gives higher overall yields and is potentially more general than those previously reported for related tribromides.