Novel asymmetric approach to proline-derived spiro-beta-lactams.

We describe a novel asymmetric approach using Staudinger chemistry to proline-derived spiro-beta-lactams. A chiral group at C-4 of the acid chloride of proline directs the stereoselectivity of Staudinger chemistry and later is sacrificed to obtain optically active 5.4-spiro-beta-lactams. The scope, limitations, and mechanistic rationale for the observed results of Staudinger Chemistry of the acid chloride of 4-alkyl(aryl)sulfonyloxy-l-proline with imines are also discussed.

Role of pyridine hydrogen-bonding sites in recognition of basic amino acid side chains.

A series of three, new artificial receptors for guanidinium and ammonium guests has been synthesized. All three receptors have highly preorganized clefts bearing two carboxylate groups. They differ in the number of nitrogen atoms contained in their clefts, as follows: four N atoms in receptor 3, three N atoms in 4, and two nitrogens in 5. Crystallographic studies have produced the solid-state structures of the following guanidinium complexes of each receptor: 3.2CH(3)CH(2)NHC(NH(2))(2)(+), 4.2CH(3)NHC(NH(2))(2)(+), and 5.2C(NH(2))(3)(+). The conformations of the receptor molecules in all three complexes are very similar. N-Alkylguanidinium guests are bound in the clefts of 3 and 4 in similar manners, despite the loss of one hydrogen-bond acceptor nitrogen in 4 and the possible hindrance of the cavity by a CH group. In the guanidinium complex of 5, neither guest enters the cavity containing two CH groups. Complexation studies were conducted in methanol by (1)H NMR titration for several guanidinium and ammonium guests, including derivatives of the amino acids arginine and lysine. Receptor 5 binds all such guests weakly (K(s) < 4000), while 3 binds most guests very strongly (K(s) > 100 000). Receptor 3 is selective for arginine versus lysine, while 4 binds lysine better than does 3. The results generally underscore the importance of receptor preorganization and hydrogen-bonding complementarity in the design of receptors that can serve as probes for biomolecules.

Circular dichroism readout of sugar recognition in the cleft of a fused-pyridine receptor.

Dicarboxamide host 2 forms 1:1 complexes with n-octyl pyranosides derived from D-glucose, D-mannose, D-galactose, D-fucose, D-lyxose, and D-arabinose. Association constants (K(a)) in the range of 77-940 M(-1) were measured in chloroform by means of induced circular dichroism and fluorescence spectroscopy. Variations in K(a) values correspond qualitatively to expected differences in hydrogen-bonding abilities of guest hydroxyl groups. Induced circular dichroism effects for complexes of saccharides bearing equatorial 3-OH, 4-OH, and 6-OH groups show that the host chromophore is twisted in a P-helical conformation. A structural model is proposed that is also consistent with the results of previous studies involving complexation of dicarboxylic acid 1 with cationic saccharides in methanol.