Synthesis and biological evaluation of novel analogues of dictyostatin
Novel analogues of the microtubule-stabilising agent dictyostatin were designed using existing SAR information from the structurally related discodermolide, synthesised by a late-stage diversification strategy and evaluated in vitro for growth inhibition
Paterson, Ian,Gardner, Nicola M.,Poullennec, Karine G.,Wright, Amy E.
p. 2443 - 2447
(2008/02/05)
Total Synthesis of Rapamycin
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
Nicolaou, K. C.,Piscopio, Anthony D.,Bertinato, Peter,Chakraborty, Tushar K.,Minowa, Nobuto,Koide, Kazunori
p. 318 - 333
(2007/10/02)
Stereoselective construction of the C21-C42 fragment of rapamycin
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Nicolaou,Bertinato,Piscopio,Chakraborty,Minowa
p. 619 - 622
(2007/10/02)
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