Homochiral chairs

As for any desymmetrization of meso compounds, enantioselectivity comes from the ability of a homochiral base to distinguish between two enantiotopic protons, in this particular case, to discriminate between the two pseudo-axial protons of the rapidly equilibrating enantiomeric half-chair conformations 51 and 52 (Scheme 25). 

The electron density and its Laplacian have been correlated exponentially with the HB distance. These results are in agreement with other reports that show the generality of this rule [120-122]. The dimers of a series of chiral and nonchiral a-aminoalcohols were studied by means of DFT methods (B3LYP/6-311++G ) (Scheme 3.14). Due to the flexibility of the molecules, twelve possible complexes can be proposed in the case of the chiral molecules. Half of them are mirror image of the other half, and thus, only six where considered. The six unique configurations studied for each dimer (Scheme 3.15) correspond to three homochiral dimers (RR or SS) and three heterochiral ones (RS or SR), and can be grouped in three chairs, Cl-3, and three boats, Bl-3, respectively. 

In gas phase, the most stable conformation always corresponds to a heterochiral one in a chair disposition and the worse one to a homochiral one in a boat disposition. The largest difference between these two extremes is 17 kJ moP1. An estimation of the solvation effect has been carried using the PCM model and water as solvent. The AGsol range between —17 kJ mol-1 for the dimer of X/Y=CF3 to —19 for X/Y=F/H. What is more important is the effect on the relative energy of the different configurations. Thus, in three of the cases studied... 

Figure 2-41. Classrooms with homochiral and heterochiral chairs in the 1980s at the University of Connecticut (photographs by the authors).

It is believed that the CNA backbone undergoes a chair inversion to adopt axial base orientations within the duplex to promote base pairing. Homo-chiral CNA complexes (d/d or l/l) of A13 or T13 are more stable than ds-DNA but show multiple transitions in the melting curve, while heterochiral CNA duplexes (d/l) are much less stable with mixed AT sequences forming only as homochiral complexes. No self-pairing of CNA strands was observed. This study demonstrates that conformational intuition of monomer structures does not easily translate to backbone conformations that favor duplex formation. Thus, CNAs are examples of nucleotidomimetics where a unique backbone conformation is only adopted through the optimization of nonadjacent contacts. 

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