Efficient Chemical Syntheses

Vol. 3 (2007/3) New Avenues to Efficient Chemical Synthesis Editors P.H. Seeberger, T. Blume... 

Seeberger PH, Blume T. New Avenues to Efficient Chemical Synthesis Emerging Technologies—Proceedings 06.3, Springer-Verlag, Berlin, 2007. 

Here, we describe, as a representative example, an efficient chemical synthesis of 4-fluorophenylpyruvic acid (Procedure 1, Section 10.5.1) followed by its biocatalytic conversion to L-4-fluorophenylalanine catalysed by the N145V mutant of PheDH (Procedure 2, Section 10.5.2). 

This process also depends on the efficient chemical synthesis of the DL-hydantoin... 

Baxendale, I.R. and Ley S.V. (2007) Solid supported reagents in multi-step flow synthesis, in New Avenues to Efficient Chemical Synthesis - Emerging Technologies (eds P.H. Seeberger and T. Blume), Springer, Berlin, Heidelberg,... 

Kovac, P, Efficient chemical synthesis of methyl (i-glycosides of 3-(1 — 6)-linked D-galacto-oligosaccharides hy a stepwise and a hlockwise approach, Carbohydr. Res., 153, 237-251, 1986. 

The recent revolution in molecular biology has brought with it an increased demand for the efficient chemical synthesis of short DNA segments, called oligonucleotides. The problems of DNA synthesis are similar to those of protein synthesis (Section 26.10) but are more difficult because of the complexity of the nucleotide monomers. Each nucleotide has multiple reactive sites that must be selectively protected and deprotected at the proper times, and coupling of the four nucleotides must be carried out in the proper sequence. Automated DNA synthesizers are now available, however, that allow the fast and reliable synthesis of DNA segments up to 200 nucleotides in length. 

However, the requirements for chemical synthesis and those for reaction dynamics studies are different. In chemical dynamics studies, we activate starting molecules at once and observe the subsequent reaction. Coherency of the activation is important but the number of activated molecules is not so important as long as we can observe them. In chemical synthesis, however, the number of molecules which participate in the reaction is much more important because it directly relates to productivity. Therefore, all the molecules in the system should be activated, but coherency of the activation is less important. We usually synthesize compounds on the 10 " -10°mol scale in laboratories and on the 10 -10 mol scale in chemical plants. Such amounts of molecules should be activated in a very short period for time-efficient chemical synthesis. 

It is also worth noting that many reactions consist of two or more reaction components in chemical synthesis, because they are useful to construct molecules however, most reaction dynamics studies deal with unimolecular reactions because it is difficult to arrange coherent collisions of two molecules. In time-efficient chemical synthesis, it is also important to know how to achieve collisions of two molecules in a very short period to accelerate bimolecular reactions. 

Sproat B, Lamond A, Beijer B, Neuner P, Ryder U. Highly efficient chemical synthesis of 2 -0-methyloligoribonucleotides and terabiotinylated derivatives Novel probes that are resistant to degradation by RNA or DNA specific nucleases. Nucleic Acids Res 17 3373-3386, 1989. 

RNA probes RNA probes bind tighter to their complementary strands than do DNA probes. Poor stability due to ubiquitous ribonucleases has hampered more widespread use of short RNA probes, as has the difficulty of efficient chemical synthesis of long RNA oligomers. Recent advances in RNA synthetic chemistry have solved the latter problem. 

The ongoing revolution in molecular biology has brought with it an increased demand for the efficient chemical synthesis of short DNA segments, called oligonucleotides, or simply oligos. The problems of DNA synthesis are... 

Although many of these highly sought-after natural products are, in principle, available from sources in nature, obtaining sufficient quantities to characterise their potential therapeutic activity is often difficult [6]. Moreover, efficient chemical synthesis of these complex compounds is extremely challenging. Investigating the biosynthetic mechanisms responsible for such attractive compounds has allowed the chanistry of polyketide-producing enzymes to be harnessed for the production of novel, biochemically bioactive natural products [7, 8]. 

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