Enantioselective Synthesis of a γ-Secretase Modulator via Vinylogous Dynamic Kinetic Resolution.

Two efficient asymmetric routes to γ-secretase modulator BMS-932481, under investigation for Alzheimer's disease, have been developed. The key step for the first route involves a challenging enantioselective hydrogenation of an unfunctionalized trisubstituted alkene to establish the benzylic stereocenter, representing a very rare case of achieving high selectivity on a complex substrate. The second route demonstrates the first example of a vinylogous dynamic kinetic resolution (VDKR) ketone reduction, where the carbonyl and the racemizable stereocenter are not contiguous, but are conjugated through a pyrimidine ring. Not only did this transformation require both catalyst and substrate control to correctly establish the two stereocenters, but it also necessitated that the nonadjacent benzylic center of the ketone substrate be more acidic than that of the alcohol product to make the process dynamic. DFT computations aided the design of this novel VDKR pathway by reliably predicting the relative acidities of the intermediates involved.

How to avoid having to run - hide - fight".

"Zero incidents" is the goal every security planner should work to achieve. The tools to build a "zero incidents" environment involve: * Acknowledging that violence is preventable. * Providing optimum customer service to every visitor, patient, family member. They are all VIP'S. * A strong emphasis on documentation. * Honoring and responding to staff intuition. *A proactive threat response program-policy. * Teaching all staff the verbal/non-verbal warning signs of violence. * Proactively contacting individuals of concern, making direct contact. * Having a strong domestic violence response and support plan. Active Shooter and Code Silver planning should also involve the crucial component of violence prevention and "zero incidents" philosophy. By merging these two, security planners will achieve the best of all possible outcomes. They will teach staff how to run, hide and fight and at the same time build a culture and workforce that provides both maximum customer support and staff awareness.

Suicide prevention in healthcare.

Healthcare facilities as growing venues for suicide by patients, family members, and others is a challenge which cannot be ignored by security and safety professionals working together with clinicians and social workers, according to the author who presents a checklist of winning strategies to achieve a "zero incidents" suicide prevention program.

Hospitals and terrorism: the realities; the future; mitigating risks.

Terrorist acts near hospitals and actual attacks on hospitals have become frequent in other countries and should not be ignored by security planners in this country, the author warns. In this article he sets forth steps which can be taken now to deal with and prevent such occurrences here.

Synthetic approaches to a chiral 4-amino-3-hydroxy piperidine with pharmaceutical relevance.

Four synthetic strategies were evaluated towards the preparation of (-)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (1), which was constructed with control over the relative and absolute stereochemistry of the 4,3-amino alcohol moiety. The first strategy employed a novel Rh(I) catalyzed asymmetric hydrogenation, while two other strategies exploited the existing stereochemistry in 2-deoxy-D-ribose, and the fourth explored both biocatalytic and classical resolution techniques as a means to impart enantioenrichment to racemic intermediates en route to targeted structure (-)-1.

Computationally designed and experimentally confirmed diastereoselective rhodium-catalyzed Pauson-Khand reaction at room temperature.

The computational analysis of the rhodium-catalyzed Pauson-Khand reaction indicates that the key transition state is highly charge-polarized, wherein different diastereoisomers have distinctively different charge polarization patterns. Experimental studies demonstrate that chloro-enynes provide the optimal σ-electron-withdrawing group to promote polarization and thereby reduce the activation barrier to provide a highly diastereoselective reaction at room temperature.

Preventing hospital gun violence: best practices for security professionals to review and adopt.

Maintaining a safe, violence-free and therapeutic work place will become the greatest challenge for hospital security professionals, the author predicts, thanks to the surge in gun sales and the increase in gun violence. By recognizing this fact and adhering to best practices, we can greatly reduce the likelihood of gun violence in hospitals, he says. In this article, he presents 18 best practices that should be reviewed for offsetting and preventing such violence.

Regio- and enantioselective intermolecular rhodium-catalyzed [2+2+2] carbocyclization reactions of 1,6-enynes with methyl arylpropiolates.

Transition metal-catalyzed [m+n+o] carbocyclization reactions provide powerful methods for the construction of complex polycyclic systems that are generally not accessible through classical pericyclic reactions. We have developed the first regio- and enantioselective crossed intermolecular rhodium-catalyzed [2+2+2] carbocyclization of carbon- and heteroatom-tethered 1,6-enynes with unsymmetrical 1,2-disubstituted alkynes. This study clearly delineates the ligand requirements for obtaining excellent regio- and enantioselectivity. Furthermore, the ability to utilize various electron-withdrawing groups, and to introduce quaternary carbon stereogenic centers, provides the level of versatility necessary for its application to target-directed synthesis. Additional studies on the development and application of this novel methodology to the total synthesis of natural products are currently underway.

Intermolecular rhodium-catalyzed [2+2+2] carbocyclization reactions of 1,6-enynes with symmetrical and unsymmetrical alkynes.

The crossed intermolecular rhodium-catalyzed [2+2+2] carbocyclization of carbon and heteroatom tethered 1,6-enynes can be accomplished with symmetrical and unsymmetrical alkynes, to afford the corresponding bicyclohexadienes in an efficient and highly selective manner.