128209-97-2Relevant academic research and scientific papers
Total Synthesis of rapamycin
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, Juergen,Scott, James S.,Spilling, Christopher D.,Watanabe, Hidenori,Wesson, Kieron E.,Willis, Michael C.
experimental part, p. 2874 - 2914 (2009/12/25)
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.
A practical synthesis of the cyclohexyl part of the immunosuppressant FK506
Haller, Bernd-Uwe,Kruber, Susanne,Maier, Martin E.
experimental part, p. 656 - 661 (2011/10/09)
Starting from the benzylidene lactone 3 of D-(-)-quinic acid the cyclohexyl fragment 15 (C-28-C-34 part) of the immunosuppressant FK506 was synthesized. Key steps include homolytic deoxygenation reactions on compounds 4 and 6 as well as a regioselective opening of the benzylidene acetal 5. Opening of the lactone 7 to provide the methyl ester 8 was followed by methylation of the hydroxy group to give 9. Further steps provided the aldehyde 12 which was elongated to the alkyne 15. This sequence provides 15 in gram quantities.
Total Synthesis of Rapamycin
Nicolaou, K. C.,Piscopio, Anthony D.,Bertinato, Peter,Chakraborty, Tushar K.,Minowa, Nobuto,Koide, Kazunori
, p. 318 - 333 (2007/10/02)
Details of the total synthesis of rapamycin (1) are reported.The synthesis required the preparation of intermediates 4-9 in nonracemic form; key coupling reactions included a chromium-mediated addition of vinyl iodide 8 to aldehyde 7 and an Evans aldol reaction to couple fragments 62 and 9.Intermediates 4 and 6 were joined through an amide bond formation to afford advanced intermediate 71.Swern oxidation of the diol in 71 was followed by a selective removal of the TES groups and a second Swern oxidation.Finally, removal of the remaining silyl protecting groups provided fully deprotected, penultimate intermediate 2 in which all carbons were in their proper oxidation state.Macrocyclization was achived through a tandem inter/intramolecular palladium-mediated Stille coupling reaction between distannylethene 3 and bis(vinyl iodide) 2.This latter process accomplished in one step the installation of the remaining two carbons of the natural product and the completion of its total synthesis. - Keywords: rapamycin, stannylethenes, Stille coupling, vinyl iodides
Studies towards the total synthesis of rapamycin: Preparation of the cyclohexyl C33-C42 fragment and further coupling to afford the C22-C42 carbon unit
Kouklovsky,Ley,Marsden
, p. 2091 - 2094 (2007/10/02)
A short and stereoselective synthesis of the C33-C42 fragment 3 of rapamycin and its coupling with the previously prepared C22-C32 fragment 2 is described. The synthesis of 3 involves the preparation of enantiom
ENANTIOSELECTIVE SYNTHESIS OF THE C(18)-C(35) SEGMENT OF IMMUNOSUPPRESSANT FK-506 USING EFFICIENT NEW METHODOLOGY
Corey, E.J.,Huang, H.Ch.
, p. 5235 - 5238 (2007/10/02)
A simple, enantiocontrolled and efficient route to an intermediate containing carbons 18 to 35 of the macrocyclic immunosuppressant FK-506 (1) is described which depends on a sequence of three enantioselective C-C bond forming reactions.
