Small molecule synthesis

Molander G, Dowdy EC (1999) Lanthanide- and Group 3 Metallocene Catalysis in Small Molecule Synthesis. 2 119-154 Monnier F, see Dixneuf (2004) 11 1-44 MoriM (1998) Enyne Metathesis. 1 133-154... 

Development of ARGET and ICAR ATRP techniques for catalyst regeneration can have profound industrial implications in polymer and small molecule synthesis because they lower the amount of necessary copper catalyst from several thousand ppm, under normal reaction conditions, to < 10 ppm [171]. 

Equations 2-27 and 2-33 and Fig. 2-2 describe the much greater difficulty of performing a successful polymerization compared to the analogous small-molecule reaction (such as the synthesis of ethyl acetate from acetic acid and ethanol). Consider the case where one needs to produce a polymer with a degree of polymerization of 100, which is achieved only at 99% reaction. Running the polymerization to a lower conversion such as 98%, an excellent conversion for a small-molecule synthesis, results in no polymer of the desired molecular weight. Further, one must almost double the reaction time (from 450 min to 850 min in Fig. 2-2) to achieve 99% reaction and the desired polymer molecular weight. For the small molecule reaction one would not expend that additional time to achieve only an additional 1 % conversion. For the polymerization one has no choice other than to go to 99% conversion. 

Olefin metathesis chemistry has had a profound impact in several areas of chemical research, including organome-tallics, polymer chemistry, and small molecule synthesis,many of which have industrial applications. For example, CM is currently utilized in the commercial preparation of several agrochemicals, polymer and fuel additives, and pharmacophores. Unlike RCM reactions, which are typically conducted under dilute... 

Mimotopes has been involved in the development, use, and commercialization of radiation-grafted polymer surfaces for multiple parallel synthesis since the late 1980s.10-12 Although other workers have reported the use of radiation-graft polymers in solid-phase synthesis,13,14 as far as we are aware, the graft polymer devices manufactured and sold by Mimotopes (SynPhase Crowns, SynPhase Lanterns) are the only current commercial products of this type. These products are presented in Fig. 1. The SynPhase Lanterns are the current design for small molecule synthesis. The initial... 

Chen C, Ahlberg Randall LA, Miller RB, Jones AD, Kurth MJ, Analogous organic synthesis of small-compound libraries Validation of combinatorial chemistry in small-molecule synthesis, J. Am. Chem. Soc., 116 2661-2662, 1994. 

The protonation of organo-rare-earth metal species through a-bond metathesis plays a key role in many catalytic applications described below. The high reactivity of rare-earth metals for insertion of unsaturated carbon-carbon multiple bonds [18], in conjunction with smooth o-bond metathesis, allows to perform catalytic small molecule synthesis. This route is atom efficient, economic, and opens access to nitrogen-, phosphorous-, silicon-, boron-, and other heteroatom-containing molecules. The most important catalytic applications of organo-rare-earth metals involving the o-bond metathesis process will be discussed in this review. 

As noted above, the field of combinatorial chemistry and multiple parallel synthesis started with libraries of peptides. In time, unusual residues crept into the products. While this evolutionis still ongoing, it is now accompanied by a major effort to produce libraries of small, drug-like molecules in library form. Many of the methods used for large molecules carry over but the largely non-iterative nature of small molecule synthesis is a significant complication. 

For small molecule synthesis, linker-functional group combinations that are labile to TFA tend to be selected. In the absence of nucleophilic functionalities such as those described above within the target molecule, simple mixtures of TFA and dichloro-methane tend to be used for release of the product from the support as this mixture is volatile and so makes work up of the reaction a simple matter of evaporation. 

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