Synthetic pathway determination

The turnover rate of a transmitter can be calculated from measurement of either the rate at which it is synthesised or the rate at which it is lost from the endogenous store. Transmitter synthesis can be monitored by administering [ H]- or [ " C]-labelled precursors in vivo these are eventually taken up by neurons and converted into radiolabelled product (the transmitter). The rate of accumulation of the radiolabelled transmitter can be used to estimate its synthesis rate. Obviously, the choice of precursor is determined by the rate-limiting step in the synthetic pathway for instance, when measuring catecholamine turnover, tyrosine must be used instead of /-DOPA which bypasses the rate-limiting enzyme, tyrosine hydroxylase. 

We have already emphasized our view that the evaluation of chemical reactions and synthetic pathways is of preeminent importance in any system for computer-assisted synthesis design or reaction prediction. The quality of the evaluation process will determine to a large extent the overall quality of such a system. 

A recent example of an attempt to determine whether using a renewable bio-logicaUy-based process for making a particular product exhibits a better environmental profile in comparison to using a synthetic pathway is the comparison of two different processes for the manufacture of the pharmaceutical intermediate 7-aminocephalosporic acid (7-ACA) as a case study [33]. The methodology used for the assessment integrates environment, health, safety, and life cycle aspects... 

As with any retrosynthetic analysis, once potential strategies are identified, one must address the problems posed by each route. In the present synthesis, such questions arise as Are the planned cyclizations likely to succeed Will the two cyclizations be conducted together or separately In what order will they occur How will the stereochemistry of the methyl group be controlled By what method will the cyclizations be conducted and what will the actual cyclization precursor(s) be How will the precursors be prepared The answers to these questions will help determine the selection of a practical synthetic pathway. 

Because each compound occupies its own well, parallel synthesis libraries require less effort for deconvolution than split libraries. Deconvolution in parallel synthesis arises from reactions that generate mixtures of diastereomers, enantiomers, or regioisomers. Split synthesis libraries require deconvolution to determine the synthetic pathway as well as any isomeric compounds that may be present. 

The primary aim of these experiments was to examine the TPD spectra of a genuine lithium alkyl carbonate formed on the surface of Au(poly) to determine whether the thermal decomposition of this UHV-synthesized material exhibits an m/e = 44 TPD spectra which resembles that observed in the TPD of d6-PC adsorbed on Li/Au(poly). The synthetic pathway employed is based on the sequential condensation of an ultrapurified alcohol (n-butanol, BuOH) onto a Li/ Au(poly) surface followed by exposure to C02 to form the desired alkyl carbonate. 

Identify possible structures consistent with data Discuss results with project team to confirm structure and to determine plausible synthetic pathway... 

The presence or absence of the enzyme, CYP17, is a major determinant of the fate of pregnenolone (or progesterone). The presence of the enzyme allows access to either the cortisol or the androgenic (sex steroid) pathways but blocks off the aldosterone synthetic pathway. The absence of the enzyme allows for the formation of progesterone and aldosterone but precludes the formation of either cortisol or androgens. (See following subsections on corticosteroid pathway and sex steroid pathway.)... 

Fig. 5 Synthetic pathway, mass spectra and fragmentation behaviour of chloronaphthoic acid. The substitution position of the carboylic group cannot be determined solely based on mass spectral data.

In Fig. 5 the synthetic pathway as well as the IR spectroscopic properties of one reference substance, 3-(bromo-4-methoxyphenyl)propionic acid methylester, are presented. However, it has to be noted that also IR spectroscopic analyses are not suitable for the determination of the bromine substitution position. 

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