Phosphoramidites mismatched

Scheme 7.10. Enantioselective 1,4-addition of Et2Zn to cyclohexenone with Cu(OTf)2-matched (S, R, R)-18 and Cu(OTf)2-mismatched (S, S, S)-18 phosphoramidites.

The configuration of the chiral BlNOLate backbone of the phosphoramidite ligand affects the rates and enantioselectivities of allylic substitution reactions. Hartwig and coworkers found that allylic substitution conducted with a catalyst derived from the simplified ligand (5a,/ )-L4 occurred more slowly than that conducted with a catalyst derived from (/ a,/ )-L4 [74]. Complexes of the mismatched (5a,/ )-L4 undergo cyclometalation slowly. The products formed from reactions catalyzed by complexes of (5a,/ )-L4 and (/ a,/ )-L4 have the opposite absolute configuration. 

The phosphoramidite of 8-Me-dG has been prepared and used to site-spedfically incorporate 8-Me-dG into oligonucleotides. In the I2-mer 5 -d(GCGCCXGCGGTG), where X = 8-Me-dG, the of the duplex was 5.5°C lower than the normal dG dC base pair. However, the of 8-Me-dG dG was 2.5°C higher than that of the mismatched dG dC base pair and the AG° values of 8-Me-dG dG and 8-Me-dG dA were 2.3 and 2.0kcal/mol lower that that of the dG mismatches. From this data, it was speculated that 8-Me-dG exists primarily in the anti conformation when paired with dC, while the syn conformation of 8-Me-dG may pair with dAMP or dGMP. ... 

New phosphoramidite building blocks for the incorporation of 1-2 histidyl residues into ODNs are reported. The interstrand cross-link (149) was introduced during solid phase synthesis using a convertible nucleoside to effect the cross-link. ODNs containing the interstrand C-C mismatch were shown to form stable duplexes, and were also substrates for T4 DNA ligase, despite the fact that the cross-link would be in the enzyme active site. 

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