Carboxy anion equivalents

Carbanions derived from orthothioformates behave as carboxy anion equivalents through alkylation with electrophiles followed by unmasking of the orthothiocarboxylate group [43]. 

Some efficient syntheses have been reported such as those of (3-hydroxy esters from tris(methylthio)methyllithium and epoxides. The case of a malate derivative from a commercially available chiral epoxide is described [286]. 

To a suspension of the compound obtained above (500 mg, 1.57 mmol) and NaHCOj (1.58g, 18.84 mmol) in MeOH/H20 (26 ml, 12 1), cooled in an ice bath, was added NBS (1.96g, 11.00 mmol). The reaction mixture was stirred at 5°C for 5 min, then at ambient temperature for 10 min. A solution of aqueous 10% Na2S20, (5 ml) was added, then the mixture was concentrated under reduced pressure to remove most of the MeOH. The reaction mixture was partitioned between H20 and Et20/hexane (1 1), then washed with water, dried (MgS04), filtered and evaporated under reduced pressure. Silica gel chromatography (35% EtOAc/hexane) afforded the (1-hydroxy ester as a colourless oil (310mg, 88%). 

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The formation of the a-bond has been carried out by conjugate addition of cyanide ion, used as a carboxy anion equivalent, to 2-phenylsulfonyl 1,3-dienes followed by functional group transformation and final... 

A carboxy anion equivalent was reported to undergo 1,2-addition in the absence of HMPA however, with 10 equiv of HMPA present only 1,4-addition was observed (eq 13). The addition of 1 equiv of HMPA promotes conjugate addition of alkyl and phenylthioallyl anions to cyclopentanones (eq 14) through the a-position, whereas in THF alone, irreversible 1,2-addition occurs with both a- and y-attack. The regioselectivities reported for the addition to cyclic enones of ketene dithioacetal anions or t-Butyllithium (eq 15) are also influenced by HMPA (and counterion). 

The cyclobutane ring was then cleaved by hydrolysis of the enamine and ring opening of the resulting (3-diketone. The relative configuration of the chiral centers is unaffected by subsequent transformations, so the overall sequence is stereoselective. Another key step in this synthesis is Step D, which corresponds to the transformation 10-IIa => 10-la in the retrosynthesis. A protected cyanohydrin was used as a nucleophilic acyl anion equivalent in this step. The final steps of the synthesis in Scheme 13.11 employed the C(2) carbonyl group to introduce the carboxy group and the C(l)-C(2) double bond. 

Detailed pictures of the iron-binding sites in transferrins have been provided by the crystal structures of lactoferrin (Anderson et ai, 1987, 1989 Baker etai, 1987) and serum transferrin (Bailey etal., 1988). Each structure is organized into two lobes of similar structure (the amino- and carboxy-terminal lobes) that exhibit internal sequence homology. Each lobe, in turn, is organized into two domains separated by a cleft (Fig. 3 and 10). The domains have similar folding patterns of the a//3 type. One iron site is present in each lobe, which occupies equivalent positions in the interdomain cleft. The same sets of residues serve as iron ligands to the two sites two tyrosines, one histidine, and one aspartate. Additional extra density completes the octahedral coordination of the iron and presumably corresponds to an anion and/or bound water. The iron sites are buried about 10 A below the protein surface and are inaccessible to solvent. 

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