Jump to main content
Jump to site search

Issue 9, 2011
Previous Article Next Article

A practical, convergent route to the key precursor to the tetracycline antibiotics

Author affiliations

Abstract

Here we describe a 5-step sequence to prepare the AB enone 1, the key precursor to fully synthetic tetracyclines, that begins with a diastereoselective Michael–Claisen coupling of two simple starting materials, a cyclohexenone (compound 2 or, in a refinement, a substituted variant, vide infra) and the isoxazole ester 3. This advance defines an 8-step linear sequence to 6-deoxytetracycline antibiotics from three components of similar complexity (cyclohexenone 2, isoxazole ester 3, and structurally diverse D-ring precursors) in which sequential diastereoselective Michael–Claisen cyclization reactions form the A- and C-rings, respectively, of the linearly fused ABCD tetracycline skeleton. In addition to providing a readily scalable, practical route to fully synthetic tetracyclines of broad structural diversity, the sequence reported comprises a series of non-obvious stereoselective transformations, including a novel means for C12a hydroxylation.

Graphical abstract: A practical, convergent route to the key precursor to the tetracycline antibiotics

Back to tab navigation

Supplementary files

Article information


Submitted
18 May 2011
Accepted
08 Jun 2011
First published
07 Jul 2011

Chem. Sci., 2011,2, 1710-1718
Article type
Edge Article

A practical, convergent route to the key precursor to the tetracycline antibiotics

D. A. Kummer, D. Li, A. Dion and A. G. Myers, Chem. Sci., 2011, 2, 1710
DOI: 10.1039/C1SC00303H

Social activity

Search articles by author

Spotlight

Advertisements