Solid-Phase Synthetic Strategies Selected Examples

5 SOLID-PHASE SYNTHETIC STRATEGIES SELECTED EXAMPLES 107 O 

Target selection and synthetic strategy in solution Compound 3.25 contains a condensed lactone and a selenium-based substituent appropriate transformations of the two groups should give access to diverse tricyclic compounds. A more radical decoration of the nucleus (3.28, Fig. 3.17) could reasonably be conceived to fuUy exploit the bicyclo[3.3. l]nonan-9-one nucleus. Literature search found arelated approach (22) where a similar, less congested tricyclic nucleus 3.29 was prepared by selenium- 

The same strategy was applied for the synthesis in solution of 3.25 (Fig. 3.20). The suitable protected P-ketoester 3.35 was easily prepared according to published procedures (23, 24) with moderate yields. Selenium-mediated endocyclization to 3.25 proceeded rather cleanly at higher temperatures but only up to 40% conversion of 3.35 any attempt to increase the conversion by further increasing the temperature or the reaction time only decomposed the starting material. The reported assessment in solution was considered satisfactory, and the authors moved to SP studies. 

Cleavage of 3.38 was attempted with an oxidation-elimination double protocol (steps c,d, Fig. 3.21) which proved to be extremely efficient in releasing pure 3.39 with 91% yield. The use of supported Se reagents ensured higher conversions and cleaner workup procedures than their counterparts in solution additional advantages provided by SPS for this project are reported below. 

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Numerous solid-phase preparations of quinazolinones have been reported. The main synthetic strategies used are summarized in Figure 15.16. Quinazolin-2,4-diones can be prepared from anthranilic acid derived ureas or from N-(alkoxycarbonyl)-anthranilamides. These reactions have been performed on insoluble supports either in such a way that the cyclized product remains linked to the support, or such that it is simultaneously cleaved from the support upon ring formation. Quinazolin-4-ones can be prepared by cyclocondensation of anthranilamides with aldehydes, orthoesters [342], or other carboxylic acid derivatives [343]. The selection of examples listed in Table 15.29 illustrates the variety of substitution patterns accessible by means of these cyclizations. 

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