Synthetic targets, and the

Given structure 1 as a target and the recognition that it contains the retron for the Diels-Alder transform, the application of that transform to 1 to generate synthetic precursor 2 is straightforward. The problem of synthesis of 1 is then reduced retrosynthetically to the simpler... 

Owing to their frequent occurrence in natural products and their synthetic utility, 2(5//)-furanones are important synthetic targets and intermediates. In considering the methods for the preparation of these compounds, we will emphasize the recent developments in this area. 

Thymidylate synthase (TS) is the rate-limiting enzyme in the DNA synthetic pathway and the target for 5-FU and folate analogs (Figure 14.3). Compared to normal tissues, TS is often overexpressed in tumor cells, probably as a result of tumor suppression loss of function, gene amplification or other mechanisms. Acute induction of TS protein as well as stable amplification of TS-specific genes may be associated with resistance to fluoropyrimidine derivatives [118, 119], and an inverse correlation between tumor TS expression and clinical response was found [120-122]. 

Weik and Rademann have described the use of phosphoranes as polymer-bound acylation equivalents [65]. The authors chose a norstatine isostere as a synthetic target and employed classical polymer-bound triphenylphosphine in their studies (Scheme 7.54). Initial alkylation of the polymer-supported reagent was achieved with bromoacetonitrile under microwave irradiation. Simple treatment with triethyl-amine transformed the polymer-bound phosphonium salt into the corresponding stable phosphorane, which could be efficiently coupled with various protected amino acids. In this acylation step, the exclusion of water was crucial. 

The strong interest in the synthesis of pyrido[4,3-h]carbazole alkaloids started in the late 1960s with the disclosure of the antitumor activity of ellipticine (228) and 9-methoxyellipticine (229) (see Scheme 2.56) in several animal and human tumor systems. This discovery made these alkaloids to important synthetic targets and induced extensive studies of structure modification. These synthetic efforts have... 

Many of the recent publications on nitrone cycloadditions have focused on the cycloaddition process itself and on the identification of the character of the reagents involved rather than with a specific synthetic target and thus, this section is potentially vast. To bring order to this wealth of information, we have identified a number of important groups of papers and will present them accordingly. We shall... 

Now diere are a variety of odier ways to disconnect R in the retrosynthetic analysis. As long as each syndietic step is valid and the target can be produced by die proposed synthetic route, dien it is a collect solution. There can be many collect synthetic solutions for a given target and the best one may depend on factors other than those related strictly to die synthetic viability. Availability of starting materials, disposal of reaction by-products, number of steps, reagent sensitivity, expected yields, number of purifications, and the stereochemistry (among odiers) all contribute to die evaluation of a synthetic route. 

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