Disconnections recognition

The information obtained by this preliminary analysis can be used not only to set priorities for the various possible Diels-Alder disconnections, but also to pinpoint obstacles to transform application. Recognition of such obstacles can also serve to guide the search for specific retrosynthetic sequences or for the highest priority disconnections. At this point it is likely that... 

With strategic bond guidance, it is easy to find 2-Gp transform disconnections even if neither FG of an effective retron is present. In the case of the bridged aldehyde 160, recognition of the strategic bond shown (in bold face) keys FGI processes in both directions from the bond, which successfully establish the aldol retron leading to molecular disconnection by a sequence of aldol and Michael transforms, to generate a simple chiral precursor.31... 

The initial step in creating a synthetic plan involves a retrosynthetic analysis. The structure of the molecule is dissected step by step along reasonable pathways to successively simpler compounds until molecules that are acceptable as starting materials are identified. Several factors enter into this process, and all are closely interrelated. The recognition of bond disconnections allows the molecule to be broken down into key intermediates. Such disconnections must be made in such a way that it is feasible to form the bonds by some synthetic process. The relative placement of potential functionality strongly influences which bond disconnections are preferred. To emphasize that these disconnections must correspond to transformations that can be conducted in the synthetic sense, they are sometimes called antisynthetic transforms, i.e., the reverse of synthetic steps. An open arrow symbol, = , is used to indicate an antisynthetic transform. 

The dimer of the hormone-receptor complex should scrutinize an infinity of sequences before finding its FIRE. The role of the hormone in the recognition of the HRE seems to be that of dramatically increasing the velocity of DNA sequence recognition, that is to say, it binds and disconnects more quickly to sequences of nonspecific DNA. When it finds the sequence of its HRE, a bond of affinity is formed that is similar to that of hormone-receptor interaction (Kd in the nM range). 

The recognition of a C2 axis of symmetry (or a plane, when the double bond was thought to have the cis configuration), allows the disconnection of the molecule into two identical moieties of indoxyl (2). The synthesis is therefore reduced to the... 

The recognition of consonant bifunctional relationships in the target molecule allows their disconnection by a retro-Claisen, a retro-aldol or a retro-Mannich condensation or by retro-Michael addition [equivalent, according to Corey s formalisation, to the application of the corresponding transforms (= operators) to the appropriate retrons]. 

Systematic bond disconnection of porantherine [151] with recognition of the double bond-carbonyl equivalence for synthesis generated a synthetic pathway which is based on two intramolecular Mannich reactions. The symmetrical nature of the amino diketone precursor identified by the retrosynthetic analysis facilitates its preparation and subsequent transformations. Moreover, all the hetero atoms (donors) are separated by odd-numbered carbon chains and such arrangements are most amenable to normal modes of assembly. 

A retrosynthetic analysis applied to each of these carboxylic acid derivatives suggests a fission of the carbon-heteroatom bond (C—O, C—X, C—N), i.e. disconnection processes. Such logic can be useful in the recognition of the reagents that could be used in the synthesis of these functional types, when these are present in more complex molecules, as illustrated below. 

The disconnection of both carbon-carbon double bonds in tetraphenylcyclo-pentadienone (14) ( tetracyclone ), in the manner of the examples above, leads to recognition of benzil and dibenzyl ketone as the reagents for its synthesis. 

The synthesis of this starting material may prove troublesome, but if an activating group (C02Et) is formally added to the methyl group, further disconnection leads to the recognition of diethyl phthalate and ethyl acetate as the reagent equivalents of the synthons (27) and (28) respectively. 

With quinoline [(100), X = H] the first retrosynthetic transform is reduction to 1,2-dihydroquinoline (cf. pyridines above) to facilitate recognition of the derived synthons obtained in the subsequent disconnection. 

The retrosynthetic approach to welwitindolinone A isonitrile (6) used by the Wood group is shown in Scheme 33. After recognition of the possibility of deriving the vinyl isonitrile fragment from a ketone, the disconnection of 6 to 140 was proposed. A literature report of a samarium (II) iodide-mediated reductive coupling of acrylates with isocyanates to give amides, which could be expected to lead to a new spirooxindole synthesis, prompted the disconnection of 140 to 141. This compound was to be obtained from the readily available cyclohexadiene derivative 143, by way of bicyclic ketone 142. 

Thus, a GSH deficit has consequences consistent with the concept of functional disconnectivity, as hypofunction of NMDA-R and alteration of dopamine signaling have been observed. When imposed on animals during development, a GSH deficit induces also a structural disconnectivity, as revealed by the decrease in dendritic spines and parvalbumin-immunoreactivity of inhibitory intemeurons in the prefrontal cortex Finally, a transient GSH deficit during brain development causes deficits in visual recognition and olfactory integration. 

The mechanism of this reaction is an example of a process whose complexity is concealed by the mirage of its apparent simplicity. The simple approach to this problem would be based on the recognition of the fact that the disconnection of the C-N bond of aziridine (I) followed by the formation of a C-0 bond suffices to explain the conversion of I to oxazolines II and III. 

In previous sections, a target was analyzed and the disconnection analysis led to reactive fragments. The disconnection process was continued until a suitable starting material was found. The actual synthesis followed the disconnection sequence to construct the molecule. If there was a bias in the construction and retrosyn-thesis. it was usually due to the special interests of the chemist, recognition of an attractive substructure, or special knowledge of one area of organic chemistry. 

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