Total synthesis of rapamycin

Nicolaou, K. C. ; Piscopio, Anthony D. ; Bertinato, Peter ; Chakraborty, Tushar K. ; Minowa, Nobuto ; Koide, Kazunori (1995) Total synthesis of rapamycin Chemistry: A European Journal, 1 (5). pp. 318-333. ISSN 0947-6539

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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 achieved 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.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons, Inc.
Keywords:Rapamycin; Stannylethenes; Stille Coupling; Vinyl Iodides
ID Code:20405
Deposited On:20 Nov 2010 14:33
Last Modified:23 May 2011 03:55

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