Based Strategies

Kuntz I D 1992. Structure-Based Strategies for Drug Design and Discovery. Science 257 1078-1082. 

Regulatory Control For most batch processes, the discrete logic reqmrements overshadow the continuous control requirements. For many batch processes, the continuous control can be provided by simple loops for flow, pressure, level, and temperature. However, very sophisticated advanced control techniques are occasionally apphed. As temperature control is especially critical in reactors, the simple feedback approach is replaced by model-based strategies that rival if not exceed the sophistication of advanced control loops in continuous plants. 

Structural subgoals may be useful in the application of transform-based strategies. This is especially so with structurally complex retrons which can be mapped onto a target in only one or two ways. It is often possible in such cases quickly to derive the structure of a possible intermediate in a trial retrosynthetic sequence. For instance, with 109 as TGT the quinone-Diels-Alder transform is an obvious T-goal. The retron for that transform can readily be mapped... 

Functional Group-based Strategy. The use of functional groups to guide the retrosynthetic reduction of molecular complexity. 

Transform-based Strategy. A strategic guide for retrosynthetic analysis in which the application of a particular powerfully simplifying transform becomes a goal. 

Despite the structural relationship between ginkgolide B and bilobalide, retrosynthetic analysis of the latter produced a totally different collection of sequences. A successful synthesis of bilobalide was implemented using a plan which depended on stereochemical and FG-based strategies. A process for enantioselective synthesis was based on an initial enantioselective Diels-Alder step in combination with a novel annulation method. 

A similar oxazolidine-based strategy was employed in the syntheses of R-(+)-anatabine (84) and (+)-benzomorphan (85), utilizing Zincke-derived salts 80 and 81, respectively (Scheme 8.4.26). In these cases, borohydride reduction, followed by cyclization, led to oxazolidines 82 and 83 as substrates for organometallic addition and subsequent elaboration to the natural products... 

Target- and System-based Strategies for Drug Discovery... 

TARGET- AND SYSTEM-BASED STRATEGIES FOR DRUG DISCOVERY... 

For patients with leukemia, the transfer of siRNA-based strategies into clinical applicability will certainly be both frustrating and time-consuming and many hurdles still have to be overcome in order to realize the therapeutic potential of siRNAs. Efficient delivery of siRNA into the leukemic stem cell and their unknown influence of the patient s immune system are the most challenging issues that need to be addressed. 

Chemistry on solid support has gained tremendous importance during the last few years, mainly driven by the needs of the pharmaceutical sciences. Due to the robust and tolerable nature of the available catalysts, metathesis was soon recognized as a useful technique in this context. Three conceptually different, RCM-based strategies are outlined in Fig. 11. In the approach delineated in Fig. 1 la, a polymer-bound diene 353 is subjected to RCM. The desired product 354 is formed with concomitant traceless release from the resin. This strategy is very favorable, since only compounds with the correct functionality will be liberated, while unwanted by-products remain attached to the polymer. However, as the catalyst is captured in this process by the matrix (355), a higher catalyst loading will be required, or ancillary alkenes have to be added to liberate the catalyst. 

The use of the modelling-based strategy above described was investigated from an action research perspective by one of us (PF) who was the chemistiy teacher of a first grade medium level school class of 26 students (14-15 years old) in Brazil. 

This classical C-P bond-forming reaction (51) has seen limited application in the glyphosate arena, presumably for lack of suitable substrates that can tolerate the vigorous reaction conditions. Typically, C-P bond formation occurs when an alkyl halide reacts with excess neat trialkyl phosphite at temperatures exceeding 100 °C, near the boiling point of the phosphite. An Arbuzov-based strategy for glyphosate requires the synthesis of the... 

RNAi-Based Strategies Against Respiratory Viruses.254... 

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