TY - JOUR
T1 - Modulating OxyB-Catalyzed Cross-Coupling Reactions in Vancomycin Biosynthesis by Incorporation of Diverse d -Tyr Analogues
AU - Ozturk, Seyma
AU - Forneris, Clarissa C.
AU - Nguy, Andy K.L.
AU - Sorensen, Erik J.
AU - Seyedsayamdost, Mohammad R.
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/7/6
Y1 - 2018/7/6
N2 - We report a general method for synthesizing diverse d-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 biosynthetic 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.
AB - We report a general method for synthesizing diverse d-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 biosynthetic 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.
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U2 - 10.1021/acs.joc.8b00916
DO - 10.1021/acs.joc.8b00916
M3 - Article
C2 - 29806454
AN - SCOPUS:85047723410
SN - 0022-3263
VL - 83
SP - 7309
EP - 7317
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 13
ER -