Carboxylic acid bioisosteres derivatives

One method for preparing imidazolylstannanes is direct metalation followed by treatment with RjSnCl [21]. l-Methyl-2-tributylstannylimidazole, derived in such manner, was coupled with 3-bromobenzylphosphonate (26) to furnish heterobiaryl phosphonate 27 [22], Under the same reaction conditions, 4-bromobenzylphosphonate led to the adduct in 69% yield, whereas only 24% yield was obtained for 2-bromobenzylphosphonate. The low yield encountered for the ortho derivative may be attributed to the steric factors to which the Stille reaction has been reported to be sensitive [23]. Heterobiaryl phosphonates such as 27 are not only substrates for the Wadsworth-Homer-Emmons reaction, but also bioisosteric analogs of the carboxylic acid group. 

Noting the similarity of tetrazole pK values to those of carboxylic acids, tetra-zoles have often been used as bioisosteric replacements for CO2H in pharmacologically active compounds. Tetrazoles alkylate and acylate on N-1 or N-2 depending on substituents at C-5, however selective 1-alkylations by quatemisation of 2-tri-w-butylstannyl derivatives have been reported. ... 

Phosphinic Acids as Bioisosteres of Carboxylic Acids and Their Derivatives... 44... 

Tetrazole derivatives are frequently used as metabolically stable surrogates for carboxylic acids (due to bioisosterism, cf. p. 274), as tetrazoles generally offer a more favorable pharmacokinetical profile [541]. Incorporation of tetrazole functionalities is especially found in antihypertensives (angiotensin II antagonists) of the sartan family, for example, irbesartan (37), losartan (38), and valsartan (39) [542] ... 

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