Transannular hemiketalization

With conditions established to determine the ratio of 44 45 acylation, 137 Pmh-containing peptides were screened as catalysts from the libraries the group had developed for group transfer reactions. Several catalysts, including those hypothesized to form a p-tum [91-93 and references therein], exhibited the capacity to reverse the intrinsic selectivity exhibited by the substrate in comparison to when NMI was the catalyst. When peptide 46 was employed, the preference of 40 for acylation at the 4" over the 11-hydroxyl was inverted from approximately 4 1 44 45 (NMI-catalyzed) to 1 5 44 45 (46-catalyzed). The 11-hydroxyl of 40 has been implicated in a macrolide-stabihzing hydrogen bond with the C9 carbonyl [94, 95]. The stmcture of 45 supports this hypothesis as it was observed to exist not as the C9 ketone, but primarily as transannular hemiketal 47, the structure of which... 

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