Unprotected N-methylanthranilic acid (1a) could be directly coupled with alcohols under Steglich esterification conditions, paving the way to a straightforward synthesis of sapintoxin D (2a) and a series of fluorescent bioprobes for drug targets of current biomedical relevance (PKC, TRPM8, SERCA).
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The volatility of simple esters of NMAA support the formation of a strong NH-to-carbonyl hydrogen bonding, as in B of Scheme 2.
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It is not clear why the esterification reaction failed with NMAA generated in situ from the DMAP-induced deprotection of its alkoxycarbonyl derivatives Since acid catalysis is required to trigger the attack of DMAP on the carbamate group, subtle acid-base effects might explain this observation.
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