Synthetic programs

The efficacy of the phenothiazines for the treatment of various psychoses led to extensive synthetic programs aimed at modulation of the biologic spectrum of these molecules. As seen elsewhere, much of this work has centered on changes of the nature of the atoms that constitute the center ring. Thus, for example, it has proven possible to replace the nitrogen atom of the phenothiazine by carbon while maintaining neuroleptic activity. 

Recently published literature described either the improvement of the strategies devoted to the synthesis of either catechins derivatives or oligomeric proanthocyanidins or the use of a synthetic program as a way to obtain... 

In CHEC(1984) and CHEG-II(1996) the most important ways to prepare the commercially available parent compounds pyridazine, phthalazine, and cinnoline were described <1984CHEC(2)1, 1996CHEC-II(6)1>. Also functionalized derivatives that are useful in synthetic programs were nicely covered. The most important type of substrates for this purpose are the easily accessible, halogenated (commonly chlorinated) derivatives exemplified by 3,6-dichloropyrid-azine, 3,4,5- and 3,4,6-trichloropyridazine, 2-substituted 4,5-dichloropyridazin-3(2//)-ones, 1,4-dichlorophthalazine, and... 

The naturally occurring 4(5//)-oxazolone antibiotic indolmycin 69 (Fig. 6.13) has been a focus of several synthetic programs since the structure was first elucidated by Schach von Wittenau and Els nearly 40 years ago. ° These syntheses can be broadly classified as either involving classical cyclization to construct the 4(5/7)-oxazolone ring or as elaboration of an existing 4(5//)-oxazolone. The classical cyclization routes will be discussed at this time, whereas routes involving elaboration of an existing 4(57/)-oxazolone will be described in Section 6.3.3. 

Fig. 2. Analogues of the spirotryprostatins from Danishefsky s synthetic program, with cytotoxicities 5000 times higher than those of the natural products.

In the course of our synthetic program on hypolipidaemic aryloxyacetic aids all the following phenols have been prepared. 

The Synthetic Program - Novel Compounds for Special Applications... 

In another example, a simple route to structure JL1, which has not been reported in the literature, was desired to support a possible synthetic program. A session on the terminal led the chemist to propose compound JL2 as a likely precursor (Scheme II). A literature search indicated its ready preparation from malic acid, thus, providing a simple solution to the problem. 

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