Total Synthesis of Rapamycin

Author: Ley, Steven V.; Tackett, Miles N.; Maddess, Matthew L.; Anderson, James C.; Brennan, Paul E.; Cappi, Michael W.; Heer, Jag P.; Helgen, Celine; Kori, Masakuni; Kouklovsky, Cyrille; Marsden, Stephen P.; Norman, Joanne; Osborn, David P.; Palomero, Maria A.; Pavey, John B. J.; Pinel, Catherine; Robinson, Lesley A.; Schnaubelt, Jurgen; Scott, James S.; Spilling, Christopher D.; Watanabe, Hidenori; Wesson, Kieron E.; Willis, Michael C.

Description: Rapamycin (1) is a macrocyclic natural product, established as a potent immunosuppressant and currently of interest to the scientific community as the framework for a series of novel anticancer drugs. Extensive studies have culminated in a new convergent total synthesis of 1, which features a number of group-derived methodologies and an unusual catechol-templating strategy for the construction of the challenging macrocyclic core. For over 30 years, rapamycin has generated a sustained and intense interest from the scientific community as a result of its exceptional pharmacological properties and challenging structural features. In addition to its well-known therapeutic value as a potent immunosuppressive agent, rapamycin and its derivatives have recently gained prominence for the treatment of a wide variety of other human malignancies. Herein we disclose full details of our extensive investigation into the synthesis of rapamycin that culminated in a new and convergent preparation featuring a macro-etherification/catechol-templating strategy for construction of the macrocyclic core of this natural product.

Subject headings: Anticancer agents; Immunosuppressive agents; Macrocyclization; Natural products; Total synthesis; Rapamycin

Publication year: 2009

Journal or book title: Chemistry: A European Journal

Volume: 15

Issue: 12

Pages: 2874-2914

Find the full text: https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.200801656

Find more like this one (cited by): https://scholar.google.com/scholar?cites=18003011445276419036&as_sdt=5,26&sciodt=0,26&hl=en

Serial number: 3290

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