Topological strategies

Structure databases are databases that contain information on chemical structures and compounds. The compounds or structure diagrams are not stored as graphics but are represented as connection tables (see Section 2.4). The information about the structure includes the topological arrangement of atoms and the connection between these atoms. This strategy of storage is different from text files and allows one to search chemical structures in several ways. 

The existence of alternative bond paths through a molecular skeleton as a consequence of the presence of cyclic subunits gives rise to a topological complexity which is proportional to the degree of internal connectivity. Topological strategies are those aimed at the retrosynthetic reduction of connectivity. 

When topological strategies are used concurrently with other types of strategic guidance several benefits may result including (1) reduction of the time required to find excellent solutions (2) discovery of especially short or convergent synthetic routes (3) effective control of stereochemistry (4) orientational (regiochemical) selectivity (5) minimization of reactivity problems and (6) facilitation of crucial chemical steps. 

Another useful topological strategy is the modification of the topology of a TGT by rearrangement to achieve any of several goals. Examples of such goals are cases (1) and (2) which follow. 

When stereochemical complexity is embedded in topological complexity, such as in complex polycyclic structures, the stereochemical strategies which are most effective are those which are linked to both complexities. A decidedly different strategic approach is appropriate for topologically simpler systems. 

These strategies guide the retrosynthetic conversion of 272 to 278 and the further conversion of 278 via 279 to 282. The r-butyl substituent actuates the clearability of the stereocenters in 279. Further retrosynthetic simplification as dictated by basic FG-, stereochemical and topological strategies then leads from 280 to 281 and to 282, a previously described substance. The successful synthesis followed closely the above outlined retrosynthetic scheme. An enantioselective process was devised for the synthesis of 281 from 282 (see Section 10.12).67, 83... 

Topological Strategy. The use of a particular bond, pair of bonds, set of bonds, or subunit as eligible for disconnection to guide retrosynthetic analysis conversely the designation of bonds or cyclic subunits as ineligible for disconnection (i.e. to be preserved). 

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