Starting material selection strategies

Rodgers, David and W. T. Wipke. Artificial Intelligence in Organic Synthesis. SST Starting Material Selection Strategies. An Application of Superstructure Search, J. Chem. Inf. Comput. Sci., 24, (1984), pp. 71-81. 

Organic Synthesis. SST Starting Material Selection Strategies. An Application of Superstructure Search. 

Starting Material Selection Strategies (SST) was an effort by the same team that uses pattern recognition to find starting materials to a given target [113]. SST uses three strategies ... 

Chemical Modification. The chemistry and synthetic strategies used in the commercial synthesis of cephalosporins have been reviewed (87) and can be broadly divided into ( /) Selection of starting material penicillin precursors must be rearranged to the cephalosporin nucleus (2) cleavage of the acyl side chain of the precursor (2) synthesis of the C-7 and C-3 side-chain precursors (4) acylation of the C-7 amino function to introduce the desked acylamino side chain (5) kitroduction of the C-3 substituent and 6) protection and/or activation of functional groups that may be requked. 

A comparatively large selection of thioureas can be formed from the reaction of amines with isothiocyanates, hence they are attractive starting materials for formation of guanidines. A common solution-phase approach to this reaction involves abstraction of the sulfur via a thiophillic metal salt, like mercuric chloride.10 For solid-phase syntheses, however, formation of insoluble heavy-metal sulfides can have undesirable effects on resin properties and on biological assays that may be performed on the product. A more relevant strategy, with respect to this chapter, is S-alkylation of thioureas and then reaction of the methyl carbamimidothioates formed (e.g., 5, Scheme 6) with amines. This type of process has been used extensively in solution-phase syntheses.1 Ul4 Two examples are shown in Scheme 6 11 the second is an intramolecular variant, which involves concomitant detrity-lation.15... 

On the other hand, most of the lyases allow a reasonably broad variation of the electrophilic acceptor component, which usually is an aldehyde. This feature, which nicely complements the emerging trend of combinatorial synthesis [38-40], makes possible a stereodivergent strategy for the synthesis of groups of stereoisomeric compounds by employing separate enzymatic catalysts to selectively produce individual diastereomers at will from the same starting material (Sect. 7). 

The wide availability of various polysaccharides provides an important source of some of the monosaccharides. Such monosaccharides are now used in organic reactions as low-cost starting materials in the synthesis of a range of simpler optically pure compounds (e.g. Expt 5.77). These synthetic strategies have been made possible from earlier work on the development of numerous selective protection methods, on the application of new selective reagents for functional group modification within the monosaccharide molecule, and on the realisation of the role of conformation in the interpretation of a reaction course. The preparative examples in this section are illustrative of these developments. 

One of the most common strategies for preparation of carboxylic acid derivatives is the acylation of nucleophiles of general formula RXH (X = NR, O, S). If the right reaction conditions are chosen and if the product is stable these reactions usually proceed swiftly and in high yield. Some carboxylic acids and nucleophiles, however, do not react smoothly or lead to unexpected results. The following sections cover a selection of representative examples of problematic starting materials. 

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