Progress to Date

Few known and thermodynamically feasible molecular structures are presently seen as impossible goals for synthesis. New transformations and effective strategies permit chemists to synthesize highly complex molecules, such as new natural compounds discovered in the continued chemical exploration of the natural world. Again, the point of such work is to develop new chemistry that permits an approach to structures of the type found in nature. This expands the power of chemistry and allows medicinal chemists to synthesize complex structures. 

There are natural targets whose syntheses have important practical applications. For example, paclitaxel (marketed as Taxol by Bristol-Myers Squibb) is an anticancer compound originally isolated from the bark of a species of yew tree, but for a long time it seemed that natural sources would not be sufficient to meet the need. Consequently, many chemists developed synthetic approaches to paclitaxel from readily available materials, although these are not yet fully practical for manufacturing. The quest continues, and a semisynthetic route has been developed starting with a compound isolated from yew needles that can be harvested without destroying the tree. An alternative approach has employed plantcell cultures in bioreactors to produce paclitaxel from yew needles (see Chapter 7 for discussion of related matters). 

Some manufacturing processes use the special properties of zeolites, inorganic substances that have interconnected cavities of well-defined size and shape. Reactions can be catalyzed inside the cavities, and they are normally selective for the shape of the substrate that can enter the cavities, and for the shape of the 

Many laboratory syntheses of important structural types of compounds are too long or complex to work well in manufacturing. Chemists working in the process area are thus often engaged in inventing new approaches that use the most modern reactions, in order to develop compact synthetic schemes with small numbers of acceptable steps. The modern reactions that make this possible are being invented by chemists involved in basic discovery and creation, usually in universities. The pressure on industrial process chemists to develop practical schemes for manufacturing important products means that they do not normally have the time for the basic research that can lead to new chemical reactions. 

Another important area is the use of photochemistry—chemistry that results from light absorption—to perform transformations that are not otherwise possible. The practical applications of photosynthesis were based on fundamental work to learn the new pathways that light absorption makes possible, but the work on these synthetic methods has also added to our basic understanding of the reaction mechanisms. The important natural process of photosynthesis also inspires some work in photochemistry, where the challenge is one of producing artificial photosynthetic systems that could use sunlight to drive the formation of energetic materials. 

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The state of development of the EDSTAC strategy, and progress to date, is described in Section 9, below. 

From the early work of Taylor [63T01] connecting dislocation behavior to observed viscoplastic shock-compression response, numerous studies have attempted to relate conventional dislocation dynamics models to experimental observations. Theory and observations consistently require unusually large numbers of mobile dislocations. Although qualitatively descriptive, progress to date on dislocation models has not proven to provide quantitative descriptions to the observations in metals. 

In addition to specific deadlines for each task and subtask, you should also consider program milestones, key pcrints in the plan at which you will want to review progress to date and make any necessary adjustments. For example, if you have adopted an element-by-element approach, you could consider completion of each PSM element as a milestone similarly, each facility s program would constitute a milestone, if that is the approach you ve chosen. 

In setting schedules and deadlines, try to be realistic while maintaining your sense of urgency. Be sure to build in sufficient time for group meetings to evaluate progress to date. Also, remember to consult those most immediately affected (for example, people whose staff will be called on) by the plan, whose other priorities must be taken into account in scheduling. 

As you know, the Task Force has spent the past five months reviewing the division s process safety management (PSM) systems as part of our company s corporate PSM initiative. We are pleased with our progress to date, and your support has enabled us to expedite the process ahead of expectations. 

Schedule. Compare progress to date with timelines established in the implementation plan. 

It s reasonable to expect that you will need to generate interim reports on the pilot test. Such reports would logically include discussion of progress to date, organized to include the key indicators you have been monitoring. In addition, you may wish to include other topics, such as ... 

This paper briefly describes our progress, to date, along the path we have proposed. 

BONTOUX L (2001) The European strategy on endocrine disrupters progress to date and EU/US cooperation. Folia Histochem Cytobiol. 39 (Suppl 2) 9-11. 

Kane JS (1991) Review of geochemical reference sample programs since G-i and W-i progress to date and remaining challenges. Spectrochim Acta 463 1623-1638. 

The major successes in treating bacterial infections that were achieved by the antibiotics discovered in the middle part of the last century are now under severe threat from the emergence of resistant strains. Very few new classes of antibacterial have been created in the past 20 years. Peptide deformylase represents a new biochemical target and clinical candidates are beginning to emerge. Chapter 3 reviews progress to date. 

Chapters 3 to 11 of the report then take up particular areas of fundamental or applied chemistry and chemical engineering. Each chapter starts with a specific list of some important challenges for the future. Then the chapter has a section on goals of the field, a section on progress to date to meet those goals, a section on challenges and opportunities for the future, and finally a section on why this is important. 

Goals in Process Systems Engineering, and Progress to Date... 

This performance code may seem equally fanciful. It is the purpose of this paper to discuss what is necessary to reach that goal and to show the progress to date. 

Virtually all therapeutic proteins must enter the blood in order to promote a therapeutic effect. Such products must usually be administered parenterally. However, research continues on the development of non-parenteral routes which may prove more convenient, less costly and obtain improved patient compliance. Alternative potential delivery routes include transdermal, nasal, oral and bucal approaches, although most progress to date has been recorded with pulmonary-based delivery systems (Chapter 4). An inhaled insulin product ( Exubera , Chapters 4 and 11) was approved in 2006 for the treatment of type I and II diabetes. 

The intention of the risk-based approach introduced by the FDA in 2002 was to modernize the FDA s regulation of the pharmaceutical quality of drugs. This was followed by the EMEAs regulation in recognition of such an important topic. This case study summarizes the progress to date for both the FDA and EMEA in the implementation of the risk-based approach. 

In summary, it is felt that progress to date with the CIS has demonstrated economic feasibility and scientific value in support of TSCA. The test before us is whether we can capitalize on this to explore the new and exciting possibilities that lie ahead in the area of using computer systems, such as the CIS, to support TSCA goals and assist in the demands of the country for a safer and healthier environment. 

Nucleic Base Acidities. The N1 and N3 Acidities of Uracil. Published in J. Am Chem. Soc. 2000, 122, 6258-6262. Our progress to date involves calculations and experiments for the determination of nucleobase activities. We have learned that there is an enormous difference in the inherent stabilities of anions at the N1 (7) and N3 (8) positions in uracil (3a, Figure 1). 

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