Structural synthetic analysis

Structural synthetic analysis, simplification and generation of the intermediate precursors of the "synthesis tree". Principle of microscopic reversibility... 

Logic-centred synthetic analysis methodology Summary 1) Structural synthetic analysis of the target molecule ... 

With these words, E. J. Corey defines for us the concept of retro-synthetic analysis for which he received the Nobel Prize in chemistry in 1990. Nowadays, it has become routine to think about a target molecule in terms of its retrosynthetic analysis. Furthermore, it is hard to imagine how chemists developed synthetic strategies prior to the formulation of these concepts in the 1960s, without thinking, at least subconsciously, in these terms about complex organic structures. 

Corey EJ, Wipke WT, Cramer RD HI, Howe WJ. Computer-assisted synthetic analysis. Facile man-machine communication of chemical structure by interactive computer graphics. J Am Chem Soc 1972 94 421-30. 

In the synthetic analysis of any organic compound, the structural features that must be taken into account are ... 

A retro synthetic analysis corresponding to the synthesis in Scheme 13.23 is given in Scheme 13.22. The striking feature of this synthesis is the structural simplicity of the key intermediate IV A synthesis according to this scheme would generate the tricyclic skeleton in a single step from a monocyclic intermediate. The disconnection III => IV corresponds to a cationic cyclization of the highly symmetric cation IVa. 

Fig. 2. Retro synthetic analysis for the dendritic structures FG, FP and X, Y are respectively interconvertible functional groups Path A is the divergent synthesis Path B is the convergent synthesis stands for the core structure Q stands for the branching repeat unit...

Corey EJ, Wipke WT, Cramer RD, Howe WJ (1972) Computer-assisted synthetic analysis. Facile man-machine communication of chemical structure by interactive computer graphics, J Am Chem Soc 94/2 421 Wipke WT, Braun H, Smith G, Choplin F, SieberW (1977) SECS — Simulation and evaluation of chemical synthesis Strategy and planning, in Computer-assisted organic synthesis, Wipke WT, Howe WJ ed, ACS Symposium Series, p 98... 

In a synthesis of tetronomycin (45) published in 1994 [14], Semmelhack et al. probe the scope of intramolecular alkoxypalladations. The retro-synthetic analysis (Scheme 4) shows that the chosen strategy exploits such Pd-catalyzed transformations even twice. The pre-target structure 46 is formally derived from 47 by Pd-mediated cy-clization. Compound 47 can be traced back via 48 to the tetrahydrofuran derivative 49, which in turn should be available by alkoxycarbonyla-tion from a precursor of type 50. 

Organic Syntheses. E. J. Corey, W. T. Wipke, R. D. Cramer, and W. J. Howe,/. Am. Chem. Soc., 94, 421 (1972). Computer-Assisted Synthetic Analysis. Facile Man-Machine Communication of Chemical Structure by Interactive Computer Graphics. E. J. Corey, W. T. Wipke, R. D. Cramer, and H. J. Howe,/. Am. Chem. Soc., 94, 431 (1972). Techniques for Perception by a Computer of Synthetically Significant Structural Features in Complex Molecules. 

This classification is also very useful for synthetic analysis, but there are additional structural features of importance for synthesis that will be demonstrated... 

Of course, such an effective windfall upon retrosynthetic analysis does not happen very often. Nevertheless, it is generally recommended that the retro-synthetic analysis of polycyclic structures should be directed first to the search of pathways that lead to one stroke framework assemblage. These possibilities can usually be accomplished with the help of cycloaddition reactions. In the course of the initial analysis, special emphasis should be given to identify structural features of the strategic core which might lead to the use of cycloaddition transforms. Let us examine a few more examples that illustrate the fruitfulness of such a retrosynthetic beginning. 

Because of instrumental limitations, most optical rotatory measurements upon polypeptides and proteins have thus far been made in the near ultraviolet and visible regions of the spectrum, a range over which the Drude and Moffitt equations are valid. For this reason, attention will henceforth be directed to featureless curves of the type shown in Fig. 1. The immediate concern will be to describe the optical rotatory properties of synthetic polypeptides with respect to conformation in order that these attributes may be subsequently employed in the analysis of protein structure. Synthetic poly-... 

The final mixture was loaded into a 50 mL Teflon-lined stainless steel autoclave and heated at 180 °C for 40 h without agitation. The solid product was filtered off, washed with distilled water, and dried at 105 °C. The product was uniform small crystals with a size of 6 pm. Powder XRD pattern characterization of the solid product showed a fully crystalline MFI structure. Elemental analysis gave an Si/Al ratio of 12-13.5, which is tunable by adjusting the ratio of source materials in the precursor gel. The absence of A1 species in the present synthetic system leads to the formation of the high-quality all-silica ZSM-5-type molecular sieve termed silicalite-I. Moreover, high-quality [B]-ZSM-5, [Fe]-ZSM-5, or [Ti]-ZSM-5-type molecular sieves could be obtained by the addition of B203, Fe2(S04)3, or Ti(OC2H5)4 to the synthetic system of silicalite-I and crystallization at 200, 180, or 175 °C for several days, respectively. 

Diversity being the core criterion, the synthesis is planned generally by forward synthetic analysis. To synthetically access the core structure of validated small molecule, e.g., a natural product scaffold, retrosynthetic analysis is important. However, for adding diversity, forward synthetic analysis is also helpful. 

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