Resin based library synthesis

A solid phase library synthesis method based on the Fischer indole synthesis was developed (Scheme A resin-capture-release method... 

Starting from resin-bound N-acylated dipeptides 11 having tryptophan or a tryptophan analog as the C-terminal amino acid, a mixture-based combinatorial library of 46,750 indolepyridoimidazoles 12 was synthesized by double cyclodehydration under Bischler-Napieralski conditions (POCl3, dioxane, 100°) (Fig. 4).23 Twenty-two tryptophan analogs, 25 amino acids, and 85 carboxylic acids were used for the library synthesis. 

The assymetric Strecker reaction of diverse imines, including aldimines as well as ketoimines, with HCN or TMSCN provides a direct access to various unnatural and natural amino acids in high enantiomeric excesses, using soluble or resin-linked non-metal Schiff bases the corresponding chiral catalysts are obtained and optimized by parallel combinatorial library synthesis [93]. A rather general asymmetric Strecker-type synthesis of various imines and a, 9-unsaturated derivatives is catalyzed by chiral bifunctional Lewis acid-Lewis base aluminum-containing complexes [94]. When chiral (salen)Al(III) complexes are employed for the hydrocyanation of aromatic substituted imines, excellent yields and enatio-selectivities are obtained [94]. 

Two of the difficulties encountered with solid-phase synthesis is quantitation and identihcation of all the products that result from resin-based solid-phase methods. Analyhcal constructs were developed to facilitate rapid quanhta-hve and quahtahve analyhcal measurements during compound synthesis and Ubrary produchon [10,11]. The analytical construct designed by Diversity Sciences possesses mulhple funchons. The construct serves as the physical link between the solid support and the site of synthesis, promotes the analyhcal analysis of a library synthesis at each step of the procedure, and also provides a facile method of bead encoding. 

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