Synthetic pathways synthesis

Many methods for chemical synthesis of a-amino acids have been estabUshed. Because excellent reviews have been pubUshed (25,38), weU-known reactions are introduced here only by their names and synthetic pathways. 

Dijbner-von Miller Synthesis. A much less violent synthetic pathway, the Dn bner-von Miller, uses hydrochloric acid or 2inc chloride as the catalyst (43). As in the modified Skraup, a,P-unsaturated aldehydes and ketones make the dehydration of glycerol uimecessary, and allow a wider variety of substitution patterns. No added oxidant is required. With excess aniline the reaction proceeds as follows ... 

Original Synthesis. The first attempted synthesis of i7-biotin in 1945 afforded racemic biotin (Fig. I). In this synthetic pathway, L-cysteine [52-90-4] (2) was converted to the methyl ester [5472-74-2] (3). An intramolecular Dieckmaim condensation, during which stereochemical integrity was lost, was followed by decarboxylation to afford the thiophanone [57752-72-4] (4). Aldol condensation of the thiophanone with the aldehyde ester [6026-86-4]... 

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

The importance of biotin in nutrition and increasing commercial needs combine to suggest the need for short and economical synthesis. Retrosynthetic analysis using cysteine as SM goal suggested a number of synthetic pathways for study, one of which has been demonstrated as shown below. 

Steps 1-2 of Figure 29.5 Acyl Transfers The starting material for fatty-acid synthesis is the thioesteT acetyl CoA, the ultimate product of carbohydrate breakdown, as we ll see in Section 29.6. The synthetic pathway begins with several priming reactions, which transport acetyl CoA and convert it into more reactive species. The first priming reaction is a nucleophilic acyl substitution reaction that converts acetyl CoA into acetyl ACP (acyl carrier protein). The reaction is catalyzed by ACP transacyla.se. 

Scheme 6. General synthetic pathways for the synthesis of group 13/15 heterocycles...

The reaction of tetraalkyldistibines with group 13-trialkyls now offers an alternative synthetic pathway for the synthesis of completely alkyl-substituted heterocycles. The first step of the reaction consists of a formation of a 1 1 or... 

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. 

The development of synthetic routes to new polyphosphazene structures began in the mid 1960 s (2-4). The initial exploratory development of this field has now been followed by a rapid expansion of synthesis research, characterization, and applications-oriented work. The information shown in Figure 3 illustrates the sequence of development of synthetic pathways to polyphosphazenes. It seems clear that this field has grown into a major area of polymer chemistry and that polyphosphazenes, as well as other inorganic macromolecules, will be used increasingly in practical applications where their unique properties allow the solution of difficult engineering and biomedical problems. 

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. 

The synthesis of 1,2,5-thiadiazoles from amino acetonitrile salts 172 was reviewed in CHEC-II(1996). Owing to the ready formation of 2-amino acetonitrile salts from aldehydes via a one-pot Strecker synthesis, this synthetic pathway... 

Precursors of phenylpropanoids are synthesized from two basic pathways the shikimic acid pathway and the malonic pathway (see Fig. 3.1). The shikimic acid pathway produces most plant phenolics, whereas the malonic pathway, which is an important source of phenolics in fungi and bacteria, is less significant in higher plants. The shikimate pathway converts simple carbohydrate precursors into the amino acids phenylalanine and tyrosine. The synthesis of an intermediate in this pathway, shikimic acid, is blocked by the broad-spectrum herbicide glyphosate (i.e., Roundup). Because animals do not possess this synthetic pathway, they have no way to synthesize the three aromatic amino acids (i.e., phenylalanine, tyrosine, and tryptophan), which are therefore essential nutrients in animal diets. 

The answer is a. (Hardman, pp 885-887.) Lovastatin decreases cholesterol synthesis in the liver by inhibiting HMG-CoA reductase, the rate-limiting enzyme in the synthetic pathway This results in an increase in LDL receptors in the liver, thus reducing blood levels for cholesterol. The intake of dietary cholesterol must not be increased, as this would allow the liver to use more exogenous cholesterol and def eat the action of lovastatin. 

In contrast to the biopharmaceuticals discussed thus far (recombinant proteins and gene therapy products), antisense oligonucleotides are manufactured by direct chemical synthesis. Organic synthetic pathways have been developed, optimized and commercialized for some time, as oligonucleotides are widely used reagents in molecular biology. They are required as primers, probes and for the purposes of site-directed mutagenesis. 

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