Versatile and facile synthesis of diverse semisynthetic tetracycline derivatives via Pd-catalyzed reactions.
A diverse collection of tetracycline derivatives has been synthesized utilizing Heck, Suzuki, and other palladium-coupling reactions via tetracycline arenediazonium and iodoarene salts. Large numbers of tetracyclines are now possible via these reactions, including numerous upper periphery derivatives of doxycycline, minocycline, sancycline, and methacycline modified at positions C7, C9, and C6-C13 on the tetracycline naphthacene ring. Application of palladium-coupling reactions to the tetracyclines has yielded new tetracycline classes with differing structural attributes, greatly increasing the structural diversity of this family of antibiotics, one of the last of the early antibiotic families to be expanded by organic and medicinal chemistry.
Nelson
Mark L
ML
Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, Massachusetts 02111, USA. mnelson@paratekpharm.com
Ismail
Mohamed Y
MY
McIntyre
Laura
L
Bhatia
Beena
B
Viski
Peter
P
Hawkins
Paul
P
Rennie
Glen
G
Andorsky
David
D
Messersmith
David
D
Stapleton
Karen
K
Dumornay
Jimmy
J
Sheahan
Paul
P
Verma
Atul K
AK
Warchol
Tadeusz
T
Levy
Stuart B
SB
D002384:Catalysis; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010165:Palladium; D013754:Tetracyclines / Q000138:chemical synthesis* / Q000737:chemistry*
D007202:Indicators and Reagents; D013754:Tetracyclines; D010165:Palladium