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A practical synthesis of the purine nucleoside phosphorylase (PNP) inhibitor BCX-4208 (1) was accomplished in three telescoped steps. Mannich condensation of the 4-benzyloxy-9-deazahypoxanthine with (3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidine and formaldehyde followed by removal of the protecting group and crystallization furnished the desired product as a hydrochloride salt in 85% overall yield and 99.8% purity. A scalable synthesis of 9-deazahypoxanthine is also reported.

The d6 complexes of formula (η5-Cp)Ru(CO)(ER3)ONO2, where ER3 = AsPh3, PPh3, P(p-anisyl)3, PPh2(o-anisyl), and P(OPh)3, were prepared by reaction of their chloro analogues with AgNO3 in CH2Cl2. They underwent moderately slow substitution of the relatively weakly coordinating nitrate by chloride in dry CH2Cl2 in the presence of excess [N(PPh3)2+]Cl-. A kinetics study showed the reaction to be first order in nitrato complex and independent of chloride salt concentration under pseudo-first-order conditions. First-order rate constants for nitrate metathesis follow the trend P(OPh)3 < PPh3 < P(p-anisyl)3 < AsPh3 ≪ PPh2(o-anisyl), with k1 at 25 °C for the first four in the series from 1.4 to 4.4 × 10-5 s-1. Activation parameters for conversion of (η5-Cp)Ru(CO)(AsPh3)ONO2 to its chloride are ΔH‡ = 17(2) kcal/mol and ΔS‡ = −21(5) eu. Even use of a slightly moist solvent increased the rate of nitrate metathesis by 20−30% without changing the form of the rate law. The complex containing PPh2(o-anisyl) was approxima...

Forodesine HCl is being investigated as a potential therapeutic target for the control of T-cell proliferation. During our ongoing process development work on forodesine HCl several novel compounds were identified as possible impurities in the process. Herein we present the synthesis of three novel compounds (2-4).

SUMMARY This paper describes the development of a computer simulation of the mechanics of rail cars during low speed collisions such as occur during automatic train coupling (ATC). The study was undertaken in an effort to determine the performance of two different types of draft-gear (elastomeric and hydropneumatic) used on vehicle consists of different size operating on the same system. Of particular concern is the case where a smaller train may be involved in a collision with a larger one. In this case, the two different draft-gear units will interact with each other, leading to effects which have not been considered by either draft-gear manufacturer. The paper includes descriptions of the mathematical models of the two types of draft-gear, the equations of motion of the system, and both predicted and measured results of ATC.

The long-term storage of human and animal cell lines is a relatively new branch of the science of cryopreservation of living organisms. The need to maintain the increasing numbers of cell lines, as they started to emerge from research laboratories from the mid-1900s, necessitated a radical approach to the problem. The realization that they could survive cryopreservation, and that a slow rate of cooling is essential for this survival, led to the eventual discovery of cryoprotectants. Subsequent development of mechanical freezers, which can accurately control the rate of cooling, now allows cells to be cryopreserved at their maximum viability. This chapter outlines the essentials steps for the successful preparation, freezing, and storage of cell lines.

The long-term storage of human and animal cell lines is a relatively new branch of the science of cryopreservation of living organisms. The need to maintain the increasing numbers of cell lines, as they started to emerge from research laboratories from the mid-1900s, necessitated a radical approach to the problem. The realization that they could survive cryopreservation, and that a slow rate of cooling is essential for this survival, led to the eventual discovery of cryoprotectants. Subsequent development of mechanical freezers, which can accurately control the rate of cooling, now allows cells to be cryopreserved at their maximum viability. This chapter outlines the essentials steps for the successful preparation, freezing, and storage of cell lines.

A major feature that distinguishes tissue culture laboratories from most other types of laboratory is the requirement to maintain the replication of a biological culture under sterile conditions (monoseptic), particularly ensuring the absence of bacteria and fungi. The facilities therefore must reflect this unusual need in the nature of equipment and laboratory design. The ideal way to plan a tissue culture laboratory is to start from scratch with a blank piece of paper. Realistically, however, this is rarely possible as budgetary constraints usually impose the need to convert existing facilities rather than build from new. This does not necessarily mean that adapted facilities will be inferior, in operation and/or safety terms, to a purpose-designed laboratory, provided that certain guidelines are followed. With this concept in mind, this chapter will both outline the basic requirements for providing a safe and efficient working environment, and suggest principles for the design of a cell culture suite.