Modulating OxyB-Catalyzed Cross-Coupling Reactions in Vancomycin Biosynthesis by Incorporation of Diverse D-Tyr Analogues

作者：Ozturk Seyma; Forneris Clarissa C; Nguy Andy K L; Sorensen Erik J^*; Seyedsayamdost Mohammad R^*

来源：Journal of Organic Chemistry, 2018, 83(13): 7309-7317.

DOI：10.1021/acs.joc.8b00916

We report a general method for synthesizing diverse n-Tyr analogues, one of the constituents of the antibiotic vancomycin, using a Negishi cross-coupling protocol. Several analogues were incorporated into the vancomycin substrate-peptide and reacted with the bio-synthetic enzymes OxyB and OxyA, which install the characteristic aromatic cross-links. We find that even small structural perturbations are not accepted by OxyA. The same modifications, however, enhance the catalytic capabilities of OxyB leading to the formation of a new macrocycle within the vancomycin framework.

• 出版日期2018-7-6