Library tetramic acids

Anionic resin capture of solution-phase library products has also been reported. The anion exchange resin A-26 hydroxide 6 was used in a dual capacity to mediate Dieckmann condensations of solution-phase library intermediates and also to affect resin capture of the formed tetramic acids as polymer-bound intermediates (Scheme 7).79 Rinsing, followed by tri-... 

Figure 6 A three-step sequence leading to tetramic acid libraries. Both parallel solution-phase (R = Me, Et) and solid-phase (R = polystyrene resin) have been reported...

The major components are series of homologous trimers, tetramers, and pentamers of the three acids 44-46, along with smaller quantities of dimers, hexamers, and heptamers. Furthermore, the secretion contains several isomers of each oligomer, furnishing a combinatorial library of several hundred macro-cyclic polyamines [51, 52]. Using repeated preparative HPLC fractionation, the most abundant trimeric, tetrameric and pentameric earliest-eluting compounds were isolated. One and two-dimensional H NMR spectroscopic analyses showed that these molecules were the symmetric macrocyclic lactones 48, 49, and 50 (m, n, o, p, q=7) derived from three, four or five units, respectively, of acid 46. Moreover, using preparative HPLC and NMR methods, various amide isomers, such as 53,54, and 55 (Fig. 9) were also isolated and characterized [51,52]. 

Another approach based on peptides is used by the Italian company Xeptagen (www.xeptagen.com). The D-PAM ligand optimized from a peptide library of 5832 randomized tripeptides is a tetramer of tripeptides linked together by a tetradentate lysine core [structure formula ([NH2-[l ]Arg-(Ji,S)Thr-[JJ]Tyr)4—(S)Lys2-(S)Lys-Gly]. All amino acids are in their artificial D-form giving the selector a higher proteolytic stability (Fassina et al, 2001). 

Recently, a lot of attention has gmie to dynamic combinatorial chemistry (DCC), in which dithiols are oxidized to libraries of disulfide macrocycles that can reversibly ring open. Different stimuli can influence the composition of the dynamic libraries. Thus, 3,5-mercaptobenzoic acid 50 or its derivatives can be converted after oxidation to such disulfide libraries containing macrocycles of different sizes, with mainly the trimer 51 and tetramer 52 [30-38]. For a thorough discussion of this... 

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