Improved synthetic pathway

Applications of the Pauson-Khand reaction. The cyclopentenone moiety (and derivatives thereof) are abundant in nature and the PK reaction has led to improved synthetic pathways to a number of natural products and compounds exerting interesting biological effects. Synthetic chemists have been attracted to the reaction because it has the potential to create highly substituted cyclopentenone rings in one step, potentially reducing the number of steps required to access complex cyclopentenone frameworks. 

Creating synthetic versions of useful natural products certainly benefits society by producing cheaper compounds. However, synthetic chemistry can also be environmentally friendly. Improved synthetic pathways can reduce the amount of toxic by-products formed during some chemical reactions. In addition, the availability of synthetic compounds eliminates the need to continually harvest large quantities of rare plants or other organisms in order to isolate the natural product. 

Fig. 5. Synthetic pathway for d-hioXin. (Lonza synthesis). An improved process uses the chiral ferrocenyldisphoshine (36) to iatroduce stereospecificity...

Overall, this route from 48 to 62 is three steps shorter than the original synthetic pathway and gives an improved yield of 49%. Final steps entailed the cleavage of the Boc-group and subsequent cis selective Lindlar hydrogenation of the triple bond to complete the total synthesis of (+)-astrophylline. 

The whole procedure, although valuable for producing high molecular weight polymers, has a weak point in the low yields obtained in the monomer synthesis. Although several attempts were made to improve the synthetic pathway, yields were never higher than 30-40%. 

These derivatives have not only provided new synthetic pathways but have shown improved thermal stability (as in the case of arsenic ylides) and a modified pattern of chemical reactivity. The donor properties of ylides 55, 24), and most of their synthetic applications 103), have been covered in other reviews and articles 3, 26) and are not duplicated here. The general organometallic chemistry of arsenic, antimony, and bismuth is the subject of the invaluable monograph by Doak and Freedman 11). The broad scope of phosphorus ylide and pentaorganophosphorane chemistry was covered in the leading multivolume series on organophosphorus chemistry edited by Kosolapoff and Maier 3, 21). Finally, the recent... 

The memory capacity of a computer is also taxed by such an organic synthesis program. At present there is no attempt to retain the whole of the synthesis tree. This means we cannot do a breadth first search. If we could do a breadth first search the efficiency of the search would be improved as we would be guaranteed the shortest possible synthetic pathway. (In a depth first search we move from A down to Bf down to C", let us say and so forth. In a breadth first search one generates all the B s, then all the C s and so forth. Each of the searches terminates when an available substance is found. The depth first search is constrained in its depth by an instruction from the... 

Revision of the synthetic pathway to improve properties, yield, purity, etc. Experiment with other starting materials, catalysts, etc. to see it a better procedure could be used... 

The concept of Green Chemistry was introduced in the early 1990s in the USA. After the introduction of the US Pollution Prevention Act, the Office of Pollution Prevention and Toxics (OPPT) explored the idea of developing new or improved chemical processes to decrease hazardous to human health and the environment. In 1991, OPPT launched a research grants program called Alternative Synthetic Pathways for Pollution Prevention. This program was focused on pollution prevention in the design and synthesis of chemicals. 

While no firm underlying mechanisms have been demonstrated, some authors have suggested that irreversible oxidation of the cobalt atom in vitamin B12 by nitrous oxide can lead to inactivation of enzymes dependent on this vitamin, with resultant metabolic aberrations. Such examples have included methionine synthetase and thymidylate synthetase, which are essential in the synthetic pathways leading to the production of myelin and thymidine, respectively. Should these enzymes be impaired during the sensitive periods of in utero development, the potential for malformations may unfortunately be realized. To date, no studies have been able to demonstrate conclusively that low-level exposure to nitrous oxide is associated with a meaningful disruption of crucial metabolic functions to produce the above-described toxicity however, measures including improved waste gas-scavenging systems should be taken to minimize exposure of personnel. 

The main drawback of dendrimers is, as we have previously shown, their lengthy step-by-step synthesis. A few ways to improve these synthetic pathways have been proposed. The obtaining of a generation using only one step is one of these ways (see above). Another way implies the use of dendrons. The dendrons are... 

As is seen in the above examples, many of the approaches that center on the replacement of a hazardous feedstock also address environmental concerns associated with the other elements of the synthetic pathway such as solvents, catalysts, etc. A concern about Green Chemistry that has been expressed is that when one aspect of a synthetic pathway is improved, additional hazards in other parts of the pathway are generated. While this concern needs to be kept in mind when evaluating a Green Chemistry process, the exact opposite is most often observed. When chemistry is... 

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