Donor group variation

Since carbohydrates constitute an inexpensive and highly modular chiral source for preparing chiral ligands," Claver et al. have reported the use of a series of thioether-phosphite" and thioether-phosphinite furanoside ligands" in the test palladium-catalysed allylic substitution reaction. In the first type of ligand, a systematic variation of the donor group attached to the carbon atom C5 indicated that the presence of a bulky phosphite functionality had a positive effect on the enantioselectivity. Indeed, the enantioselectivity was controlled mainly by the phosphite moiety. This was confirmed by the use of a ligand... 

Fig. 2.U The variation of logA , with of the buffer for reaction (2.166). The buffers used are Mes(l), 3,5-lutidine(2), 3,4-lutidine(3), 2,4-lutidine(4), 1-Meimid(5), Hepes(6), triethanolamine(7), 4-Meimid(8), l,2-diMeimid(9), Ted(lO) and Ches(ll). The curve drawn is calculated for = 1.1 x 10 M s and a pA n for the enzyme donor group of 7.6. Reprinted with permission from R. S. Rowlett, and D. N. Silverman, J. Amer. Chem. Soc. 104, 6737 (1982). (1982) American Chemical Society.

Such shift variations, as in the cases of benzylic and 7-norbornenyl fluorides, where the presence of donor groups leads to deshielding appear to be counterintuitive. 

Recently, Lazo and co-workers reported a combinatorial library of PTPIB inhibitors based on a pharmacophore derived from the structure-activity relationships for several natural product inhibitors of PSTPases such as oka-daic acid, microcystins and calyculin A [425, 426], The pharmacophore model involved a carboxylate, a non polar aromatic group and hydrogen-bond acceptors and donors and was used as a platform for functional group variation. Among the 18 library compounds generated by parallel solid-phase chemistry, a non-competitive inhibitor for PTPIB was identified (library 41, Kj=0.85 jiM) [425] and as well a serine/threonine phosphatase inhibitor (library 42, IC50 < 100 /iM) [426],... 

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