Hydroxylation sites methyl ester

Ohba and co-workers have demonstrated that A -protected a-amino esters are compatible with the Schollkopf oxazole synthesis cf., 38->39). In the case of ammo esters derived from natural amino acids (e.g., 38), the presence of an additional acidic N-H bond in the AABoc ester substrate necessitated the use of an added excess of metalated isocyanide (2.5 equiv was found to be optimal) to obtain maximal yields. Under optimized conditions, oxazoles (39) were obtained in good yield from iV-Boc glycine, alanine, and phenylalanine. Oxazole formation from iV-Boc serine (which possesses an additional acidic site in its hydroxylic side chain) proceeded in good yield (66%) using 3.5 equiv lithiated methyl isocyanide. Notably, no epimerization was detected in the reaction of N-Boc alanine methyl ester with lithiated methyl or ethyl isocyanide under these conditions. Minor epimerization was observed (91-92% ee product) with substrates that lacked a carbamate NH hydrogen e.g., A -Boc proline methyl ester), however. ... 

Related to a class of a,y-diketoacids that has previously been shown to bind to NS5B [64], is the mono-ethyl ester of meconic acid 25. This compound was identified as a selective inhibitor of NS5B HCV polymerase (IC50 = 2.3 pM) and is competitive with the diketoacids. SAR studies have demonstrated the requirement for the carboxylic acid. A variety of different permutations of esters, acids, amides, and decarboxylated compounds were prepared without any improvement in binding affinity or in the cell-based replicon assay [65]. The 4,5-dihydroxypyrimidine-6-carboxylic acids, a hybrid of the a,y-diketoacids and meconic acid, envisioned as chelators of the essential Mg2+ ions in the active site of NS5B, are also active in the polymerase assay (26, IC5o = 5.8pM). While alkylation of the phenol of the hybrid is tolerated, methylation of the heterocyclic hydroxyl groups or the carboxylic acid, as well as decarboxylation, leads to... 

A similar strategy has been employed in construction of SA multilayers from methyl 23-(trichlorosilyl)tricosanoate, H3C02C-(CH2)22SiCl3 [194]. Chemisorption of this surfactant onto substrates resulted in a well-behaved SA monolayer whose exposed ester moieties could be reduced to alcohol groups which, in turn, could serve as the reactive sites for chemisorption of a subsequent layer of surfactant. Repetition of this process led to structures which contained up to 25 equally thick layers in a SA multilayer (Fig. 21) although surface characterizations indicated an increasing disorder in the surface hydroxyl groups [176, 194]. 

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