Substrate Synthesis

The deleterious effects of catalyst poisoning when carrying out asymmetric hydrogenations at low catalyst loading caimot be overemphasised. In order to eliminate the possibility that the substrate synthesis introduced inhibitory impurities, an alternative synthetic protocol was examined (Scheme 7.4). The use of a brominating agent and an expensive palladium catalysed step in the initial route could limit the development of this as an economically favourable process and this was further motivation to examine alternative routes to the hydrogenation substrate. 

Huang, S.S., Yu, H. and Chen, X. (2007) Disaccharides as sialic acid aldolase substrates synthesis of disaccharides containing a sialic acid at the reducing end. Angewandte Chemie-International Edition, 46, 2249-2253. 

While we were concerned by the potential problems with our desired reaction, particularly the poor dienophilicity of indoles and the failure of 54 to cyclize under stepwise cyclization conditions, we were nonetheless inspired to pursue this potentially direct strategy. The successes of Marko and Rosenmund in related systems (51 —> 52 and 55 —> 56, respectively), the ease of substrate synthesis, and the significant utility of the reaction products compelled us to evaluate Zincke... 

Platt, F. M. and Butters, T. D. Inhibition of substrate synthesis a pharmacological approach for glycosphingolipid storage disease therapy. In F. M. Platt and S. U. Walkley (eds), Lysosomal Disorders of the Brain. New York Oxford University Press, 2004, pp. 381 108. 

Many of the enone substrates used in polyamino acid-catalysed epoxidation reactions can be made via a simple aldol condensation, which leads directly to the desired enone after in situ dehydration. Enones that cannot be synthesised by the above route may often be synthesised using standard Wittig chemistry, (Scheme 6). The above methods of substrate synthesis provide compounds with a variety of groups R and enabling the incorporation of both aliphatic and aromatic moieties into the enone structure. 

Chang. S.K. and Hamilton, A.D. (1988) Molecular recognition of biologically interesting substrates Synthesis of an artificial receptor for barbiturates employing six hydrogen bonds. J. Am. Chem. Soc., 110, 1318-1319. 

M. Titanate-mediated transesterifications with functionalized substrates. Synthesis 1982, 138— 141. 

Substrate reduction therapy (SRT) involves the inhibition of substrate synthesis to a level where the load falls within the capacity of the mutant enzyme that exhibits residual function (Platt and Jeyakumar, 2008). Thus this approach, as in the case of pharmacological chaperones, may be dependent on the type of mutation responsible for disease in an individual. 

This innovation has the verisimilitude of great practical worth. To date, attainment of high enantioselectivities in the hydrogenation of a-arylenamides is singularly associated with the Me-DuPHOS-Rh and Me-BPE-Rh catalysts. However, there remained a major obstacle to the establishment of a commercially practicable process for the production of a-1 -arylalkylamines—no viable synthesis of a-arylenamides existed. In asymmetric catalysis, the actual catalytic step is only one aspect of the entire process. A muted yet crucial facet of industrial asymmetric catalysis deals with substrate synthesis. The great emphasis placed on the catalytic step often obscures the need for economical production of the substrate. Many potential asymmetric catalytic reactions have been rendered impractical because of inaccessibility of the requisite substrates. 

Ligand and substrate synthesis, reaction parameters, enantio-enrichment... 

Substrate synthesis, reaction parameters, enantioenrichment via biocatalysis, catalyst handling, economic considerations Catalyst screening, substrate design, process optimization, application of Josiphos ligands, ligand synthesis, scale-up Production considerations, comparison with classical methods... 

This is also a technology-driven strategy where the emphasis is on the adaptation of known catalysts and the development of new processes. Usually the domain of fine chemicals companies who want to apply their in-house technology to a selected molecule (family) where substrate synthesis and backintegration are important considerations. 

Discussion of methods, substrate synthesis, continuous process, membrane reactor, enzyme deactivation Development phases, route comparison, test of many alternative methods, technical catalyst preparation, process optimization, ee enrichment via crystallization, industrial assessment... 

Dips containing benzoate, alone or in combination with AA, provided short-term protection against browning in Delicious and Winesap plugs but induced browning in samples stored 6 or more hours. Induced browning by benzoate may be an indication of its conversion to a PPO substrate or its stimulation of substrate synthesis by enzymes at the cut surface. Benzoic acid in plants is derived from phenylalanine via trans-cinnamic acid (55-56) which is also a precursor of caffeic acid and other PPO... 

Early transition metal carbenoid reagents in epimetallation and metallative dimerization of unsaturated substrates (synthesis of heterocycles with participation of carbenoid reagents) 01JOM(617-618)148. 

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