Biotransformation-mediated synthesis of (1S)-1-(2,6-dichloro-3-fluorophenyl)ethanol in enantiomerically pure form

An efficient four-step biotransformation-mediated synthesis of (1S)-1-(2,6-dichloro-3-fluorophenyl)ethanol in enantiomerically pure form is described. This compound is a key intermediate required for the preparation of PF-2341066, a potent inhibitor of c-Met/ALK that is currently in clinical development. The described synthesis was used to manufacture 6 kg of the title compound and can also be employed to produce the corresponding (1R)-enantiomer.     

Adsorption and diffusion of argon in disordered nanoporous carbons

Application-specific optimization of disordered nanoporous carbons remains a formidable challenge due to the difficulty in accurately characterizing their microstructures with current empirical methods. Using molecular simulation techniques, we investigated the adsorptive and diffusive behavior of argon in three models of disordered nanoporous carbons. We found that the structural and morphological differences between these models gave rise to distinct phenomenological properties. The adsorptive behavior of argon in both the low and high pressure regimes was enhanced dramatically in the models with more crystalline microstructures. As for dynamic properties, we found that the adsorbent’s structure and energetic topology significantly alters the rates of diffusion as well as the characteristics of the underlying diffusion mechanisms.     

Two techniques for PIV-based aeroacoustic prediction and their application to a rod-airfoil experiment

In this paper, we discuss techniques by which the aeroacoustic properties of the turbulent flow in a rod-airfoil benchmark experiment can be inferred from time-resolved PIV measurement. While acoustic measurements can be made directly using microphones, the proposed techniques provide a means to directly link acoustic waves with specific flow events, which is invaluable in devising noise mitigation strategies. The approaches are possible thanks to recent improvements in digital and camera technology that can provide time-resolved measurements in air flows, necessary for the determination of unsteady flow quantities related to aeroacoustic production. Both techniques are based on Curle’s acoustic analogy, where one is based on Lagrangian determination of the required quantities, while the other requires all flow quantities to be converted into Fourier modes. Application of both techniques yields results that are in reasonable agreement with microphone noise measurements for the rod-airfoil experiment.     

Nmr and Mass Spectroscopic Studies of the Competitive-Angiotensin II Antagonist “Sarmesin”

Fast atom bombardment mass spectrometry (FAB-MS) and high resolution (400 Mz) proton nuclear magnetic resonance (NMR spectroscopy) on the competitive angiotensin II antagonist, |Sar¹, Tyr(Me)⁴ (ANGII (Sarmesin) and its he-ptapeptide homolog, [Tyr(Me)³ |ANGIII, yield spectra which provide confirmation of structure and molecular weight. The characteristics of the spectra are discussed and compared with the spectra of natural ANG II, ANG III and |Sar¹|ANG II. The NMR data are suggestive of interactions in angiotensin between: 1) the phenolic hydroxyl group and the imidazole ring, and 2) the N-terminal amino group and the Tyrring. These interactions may be important for the formation of the proposed charge transfer system in angiotensin II involving the phenoxyl and α-carboxylate groups.     

An advanced tabu search for solving the mixed payload airlift loading problem

This article describes a new, two-dimensional bin packing algorithm that feasibly loads a set of cargo items on a minimal set of airlift aircraft. The problem under consideration is called the Mixed Payload Airlift Loading Problem (MPALP). The heuristic algorithm, called the Mixed Payload Airlift Loading Problem Tabu Search (MPALPTS), surpasses previous research conducted in this area because, in addition to pure pallet cargo loads, MPALPTS can accommodate rolling stock cargo (ie tanks, trucks, HMMMVs, etc) while still maintaining feasibility. To demonstrate its effectiveness, the load plans generated by MPALPTS are directly compared to those generated by the Automated Air Load Planning Software (AALPS) for a given cargo set; AALPS is the load planning software currently mandated for use in all Department of Defense load planning. While more time consuming than AALPS, MPALPTS required the same or fewer aircraft than AALPS in all test scenarios.