Synthetic pathways, tree

The option "Select" can be used to copy on the "clipboard" any figure appearing in the windows of the CHAOS program. For example, you can copy synthetic pathways obtained with the option "Synthetic sequence" (Process menu), synthesis trees, etc. 

The memory capacity of a computer is also taxed by such an organic synthesis program. At present there is no attempt to retain the whole of the synthesis tree. This means we cannot do a breadth first search. If we could do a breadth first search the efficiency of the search would be improved as we would be guaranteed the shortest possible synthetic pathway. (In a depth first search we move from A down to Bf down to C", let us say and so forth. In a breadth first search one generates all the B s, then all the C s and so forth. Each of the searches terminates when an available substance is found. The depth first search is constrained in its depth by an instruction from the... 

Fig. 1.3 A tree of synthetic pathways from available starting materials to the target.

For each target molecule Z there is a set of atoms A whose FIEM(.4) contains all conceivable synthetic pathways for Z. The synthetic pathways of Z in its universal FIEM(j4) of syntheses are representable by a graph, the universal tree of syntheses of Z. A perfect computer program of synthetic design would find the best synthesis of Z which is contained in the universal tree. 

For example, we can generate a tree of reasonable synthetic pathways that has to be taken into consideration for an n atom target... 

The synthetic design program EROS and its predecessors generate a tree of BE-matrices starting from one BE-matrix which refers to the synthetic target. This tree may be interpreted as a tree of synthetic pathways. 

Synthetic highlights The partial synthesis of paclitaxel was necessary to enhance the availability of the drug substance and avoid unsustainable use of yew trees. Many different synthetic routes have been reported and three inventive pathways for the enantioselective or site-selective approaches to various segments of the paclitaxel molecule are described. These are aU promoted by organometal catalytic complexes. Reactions presented include use of the intramolecular Heck reaction in the synthetic pathway to baccatine III the Sharpless reaction and the introduction of a trifunctional catalyst for biomimetic synthesis of chiral diols synthesis of the paclitaxel side-chain and use of a Zr-complex catalyst in the reductive N-deacylation of taxanes to primary amine, the key precursor of paclitaxel. 

The "principle of microscopic reversibility", which indicates that the forward and the reverse reactions must proceed through the same pathway, assures us that we can use the same reaction mechanism for generating the intermediate precursors of the "synthesis tree", that we use for the synthesis in the laboratory. In other words, according to the "principle of microscopic reversibility", [26] two reciprocal reactions from the point of view of stoichiometry are also such from the point of view of their mechanism, provided that the reaction conditions are the same or at least very similar. A corollary is that the knowledge of synthetic methods and reaction mechanisms itself -according to the electronic theory of valence and the theory of frontier molecular orbitals- must be applied in order to generate the intermediate precursors of the "synthesis tree" and which will determine the correctness of a synthesis design and, ultimately, the success of it. 

Once the "synthesis tree" has been elaborated, we must proceed to the evaluation of the alternative pathways and compare them with possible synthetic schemes in order to optimise the chosen route and make it as self-consistent as possible. However, all synthetic plans must be flexible enough to allow new alternative solutions when things do not happen as anticipated. In this sense. Woodward referred very often to opportunism and of taking advantage of the "surprises" which may occur during the execution of a synthesis. Through the different stages of a synthesis new aspects may evolve and even important discoveries may be made. Such was the case, for instance, in the vitamin B12 synthesis in which the considerations of the stereochemistry of an intermediate, opposite to the one anticipated, led Woodward to the discovery of the principle of conservation of orbital symmetry [29]. 

The synthetic examples in this section show that a biosynthetic pathway can be u.sed to generate a synthetic tree, which can be of great utility and simplifies the task of growing the synthesis tree. If the biosynthesis is unknown one can turn to other processes for guidance. 

In a complex synthetic tree (see Figure 10.18), 46 which pathway is the best As stated by Hendrickson, "selection, not generation, is the central problem."l47 xhe tree must be first simplified and then subdivided. 

A target may resist hydrolysis or chemical degradation, or the degradation products may not yield useful information. It is also common that insufficient material exists for proper analysis. In these cases, an alternative degradation technique is available that uses the ionizing electron beam of a mass spectrometer. The ionization pathways available from electron impact in the mass spectmm are bond fission processes that occur by known and predictable pathways. Indeed, each pathway usually follows analogous chemical reaction pathways in a retro-synthetic manner. It therefore follows that an examination of mass spectral ionization patterns can give clues for suitable disconnections and a synthetic tree. 

As natural rubber is a product of nature, its properties are determined by the biochemical pathway by which the polymer is synthesized in the plant. In the case of natural rubber the polymerization process cannot be tailored like that of synthetic rubbers. The only option to modify natural rubber is after it has been harvested from the tree. The important modified forms of natural rubber include hydrogenated natural rubber, chlorinated natural rubber, hydro-halogenated natural rubber, cyclized natural rubber, depolymerised liquid natural rubber, resin modified natural rubber, poly(methyl methacrylate) grafted natural rubber, poly(styrene) grafted natural rubber, and epoxidized natural rubber [33,34]. Thermoplastic natural rubber prepared by blending natural rubber and PP is considered as a physically modified form of natural rubber. 

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