Synthetic step

Di- and trinucleotides may be used as units instead of the monomers. This convergent synthetic strategy simplifies the purification of products, since they are differentiated by a much higher jump in molecular mass and functionality from the educls than in monomer additions, and it raises the yield. We can illustrate the latter effect with an imaginary sequence of seven synthetic steps, c.g. nucleotide condensations, where the yield is 80% in each step. In a converging seven-step synthesis an octanucleotide would be obtained in 0.8 x 100 = 51% yield, compared with a 0.8 x 100 = 21% yield in a linear synthesis. 

A multistep synthesis is strategically designed such that the labeled species is introduced as close to the last synthetic step as possible in order to minimize yield losses and cost. Use of indirect reaction sequences frequently maximizes the yield of the radioactive species at the expense of time and labor. 

In the BASF synthesis, a Wittig reaction between two moles of phosphonium salt (vitamin A intermediate (24)) and C q dialdehyde (48) is the important synthetic step (9,28,29). Thermal isomerization affords all /ra/ j -P-carotene (Fig. 11). In an alternative preparation by Roche, vitamin A process streams can be used and in this scheme, retinol is carefully oxidized to retinal, and a second portion is converted to the C2Q phosphonium salt (49). These two halves are united using standard Wittig chemistry (8) (Fig. 12). 

DOPA in the bloodstream can be taken up into neural tissue and into tissue devoid of tyrosine hydroxylase, thus bypassing the rate-limiting enzymatic synthetic step (35). Uptake of DOPA by the brain is the basis of the therapeutic effect of DOPA in the treatment of Parkinson s disease (a... 

This procedure provides a method for functionalizing the pyrrole ring in the 3-position, normally a difficult synthetic step when conventional electrophilic substitution is used, The technique has been extended to... 

The process of selecting a protective group involves a number of discrete steps. First, the proposed scheme is summarized, with reactants, reaction conditions, and products delineated for each synthetic step. Next, the relative reactivities of the functional groups in each reactant... 

This remarkable process allows the joining of three components in one synthetic step. This methodology was applied to the syntheses of several juvenile hormones and famesol. 

Schroder and Witt ° have reported the synthesis of crown ethers having fluctuating ring sizes which they have termed breathing crown ethers . The structures are based on the bullvalene subunit and, as the tetracyclic subunit undergoes Cope rearrangement, the size of the macroring likewise varies. The synthetic steps follow the conventional routes used for the preparation of crown ethers and are illustrated in Eq. (3.44). 

It is convenient in synthetic transformations involving more than one step simply to list all the reagents with a single arrow. Individual synthetic steps are indicated by number. Numbering the individual steps is essential so as to avoid the implication that everything is added to the reaction mixture at the same time. 

C alkylation was used in the corydaline synthesis 194). LukeS and Dedek 195) obtained on methylation of l-methyl-2-ethylidenepyrrolidine a C-alkylation product, i.e., l-methyl-2-isopropyl-/l -pyrroline (106). Alkylation of the same enamine with ethyl bromoacetate was the first synthetic step in the preparation of D,L-pseudoheliotridane 196). 

Because of the many possible reactions of aldols, it is generally recommended to use a freshly distilled product for further synthetic steps. 

The conversion of alkyl halides to aldehydes is a synthetic step... 

Scheme 10.26 Partial biosynthetic pathway of fosfomycin and bialaphos. Both pathways use a homologous set of enzymes for the synthetic steps leading from phosphoenolpyruvate (PEP) to phosphonoacetaldehyde (PAA). The conversion of hydroxypropylphosphonic acid (HPP) to fosfomycin is catalyzed by the epoxidase HppE. Propenylphosphonic acid (PPA), however, is not converted to fosfomycin.

Intramolecular allylzinc aldehyde additions lead, in one synthetic step, to bicyelic a-methylene-y-lactones41. Interestingly, the (Z)-isomer gave only the r/5-fused bicyclic products, which arises from a. vyw-selectivc addition, while the ( >isomeric bromide furnished a cisjtrans mixture (yield 56%, cisjtrans 72 28)41 indicating that the double-bond torsion and the intramolecular carbonyl addition have similar rates. A similar sequence was the key step in a confertin synthesis28. 

Zinc bromide promoted addition of a functionalized benzyl Grignard reagent to the a,/ -unsat-urated y-lactone, 3-(4-methylphenylsulfinyl)-2(5//)-furanone, via a zinc-chelated intermediate, gave, after several synthetic steps, (-)-podorhizon with 95% ee18. 

If methvloctvldichlorsilane is used as the reagent in a sequence of synthetic steps, an oligomeric phase can be built up on the surface. 

Processes consisting of two or more synthetic steps carried out in the same flask without isolating any intermediates have been widely investigated in the last decade due to their ecological and economic advantages when compared to a stepwise procedure. In this respect the Diels-Alder reaction is a frequent example. 

The production of aromatic bromo-compounds is rarely an end in itself. More commonly the bromo-compounds are precursors for some further synthetic steps. Often, the bromine is replaced either in a direct substitution reaction or via... 

The use of molecular biology methods, described in Section 5.3 seems to be especially worthwhile as it offers novel possibilities of optimization on process adjustment. Directed evolution leads to the formation of new biocatalysts with improved characteristics (selectivity, activity, stability, etc.). Incorporation ofnon-proteinogenic amino acids makes it possible to reach beyond the repertoire of building blocks used by nature. The prospect of bioconjugate preparation offers the possibility to form functional clusters of enzymes and to perform multiple synthetic steps in one pot. 

As discussed in Sections 14.2 and 14.3, a critical difference between batch and continuous processes lies in equipment utilization. The complexity (or simplicity) of synthesis and isolation is a critical factor in determining whether a whole process is viable for switching from B2C. Given that it takes an average of eight synthetic steps to produce an API from raw materials [51], it is clear that the average API manufacturing process is probably too complex in its current form. Reduction in the number of process steps for a continuous process will, to a first approximation, reduce the plant costs pro rata. 

Synthetic constraints—such as difficulty, yield, management of starting materials, and intermediates—will naturally restrict the diversity of compounds that are made [7]. In silico designs with scaffolds that utilize similar synthetic steps will naturally be favored over those that are not. These pressures to make a small number of compounds with limited scaffold variability require computational methods to make exquisitely accurate predictions The... 

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