Polymersupported Acylanion Equivalents [30

Polymer-supported carbanion equivalents are the obvious supplement to polymer-supported access to reactive electrophiles either by oxidizing polymers or by release of carbenium ions. The combination of an oxidizing resin with a support carrying carbanion equivalents will be especially rewarding, enabling reaction sequences with C-C coupling steps and thus opening access to a wealth of potentially relevant products.

Bestatin 6a (Figure 3.6.8) is the lead structure of a family of highly potent protease inhibitors containing the 3-amino-2-hydroxy-4-phenylbutanoic acid as the active, isosteric motif, mimicking the tetrahedral intermediate formed during amide bond cleavage [31]. Several clinically employed HIV-protease inhibitors are from this class of compound. The oxidized a-keto-^-amino derivatives have also

Fig. 3.6.7. Isolation and storage of pure peptide aldehydes by using an improved catch-and-release procedure [39]. Purity of peptide aldehydes was determined by RP-HPLC (214 nm).

been described as powerful inhibitors [32, 33]. Several bestatin syntheses have been described, although syntheses of variations of the general structure 6 are tedious and have been limited so far, especially in respect of the 4-substituent [34, 35]. Thus, a method enabling efficient variation of the target structure in all relevant positions would be highly desirable. Such a diversity-oriented procedure based on novel polymeric reagents was the objective of our work.

In Nature the ubiquitous a-hydroxy carbonyl motif is provided by acyl anion equivalents derived from thiamine pyrophosphate (vitamin B1) as enzymatic co-factor. Thus our synthesis of compounds 8 was based on the construction and in-

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