250355-82-9Relevant academic research and scientific papers
A second-generation total synthesis of (+)-phorboxazole A
Smith III, Arnos B.,Razler, Thomas M.,Ciavarri, Jeffrey P.,Hirose, Tomoyasu,Ishikawa, Tomoyasu,Meis, Regina M.
, p. 1192 - 1200 (2008/09/17)
(Chemical Equation Presented) A highly convergent second-generation synthesis of (+)-phorboxazole A has been achieved. Highlights of the synthetic approach include improved Petasis-Ferrier union/rearrangement conditions on a scale to assemble multigram qu
Stereocontrolled synthesis of spiroketals via a remarkable methanol-induced kinetic spirocyclization reaction
Potuzak, Justin S.,Moilanen, Sirkka B.,Tan, Derek S.
, p. 13796 - 13797 (2007/10/03)
A methanol-induced kinetic spiroketalization reaction has been developed for the stereocontrolled target- and diversity-oriented synthesis of spiroketals. In contrast to existing methods for spiroketal synthesis, this reaction does not depend on thermodyn
(+)-Phorboxazole a synthetic studies. A highly convergent, second generation total synthesis of (+)-phorboxazole A
Smith III, Amos B.,Razler, Thomas M.,Ciavarri, Jeffrey P.,Hirose, Tomoyasu,Ishikawa, Tomoyasu
, p. 4399 - 4402 (2007/10/03)
(Chemical Equation Presented) A second generation total synthesis of the potent antitumor agent (+)-phorboxazole A (1) has been achieved. The cornerstone of this approach comprises a more convergent strategy, involving late-stage Stille union of a fully e
Phorboxazole B synthetic studies: Construction of C(1-32) and C(33-46) subtargets
Paterson, Ian,Steven, Alan,Luckhurst, Chris A.
, p. 3026 - 3038 (2007/10/03)
The convergent syntheses of the C(1-32) and C(33-46) domains of phorboxazole B are described. An iterative cyclocondensation strategy exploited the Jacobsen hetero-Diels-Alder (HDA) reaction as a platform for the synthesis of both the C(5-9) and C(11-15) tetrahydropyran rings. The use of 2-silyloxydiene coupling partners bearing an increasing resemblance to the phorboxazole skeleton was found to lead to a reduction in diastereoselectivity, however, in the case of the C(11-15) ring. The coupling of aldehyde 21 and 2-silyloxydiene 20 by this route provided a C(1-32) fragment which was elaborated to the macrolide core of phorboxazole B. The synthesis of the C(33-46) domain involved a Nozaki-Kishi coupling of aldehyde 31 and vinyl iodide 39. The syntheses of 31 and 39 were highly diastereoselective: an Evans [Cu(Ph-pybox)](SbF6)2-catalysed Mukaiyama aldol reaction formed the cornerstone of the synthesis of 31 whilst a Nagao-Fujita acetate aldol reaction provided a convenient means of installing the sole stereogenic centre of 39.
Synthetic studies directed toward the phorboxazoles: Preparation of the C3-C15 bisoxane segment and two stereoisomers
Greer, Patrick B.,Donaldson, William A.
, p. 6009 - 6018 (2007/10/03)
A synthetic approach to the C3-C15 segment of the cytotoxic marine metabolite phorboxazoles is described. This segment consists of a methylene linked bisoxane structure. The first pyran ring was constructed by a Lewis acid catalyzed diene-aldehyde cyclocondensation. The β-C-glucoside substitution pattern of this ring was established by a stereoselective allylation. Ozonolysis of vinyl group and enantioselective allylation of the racemic aldehyde generated two separable homoallylic alcohols (-)-22 and (+)-23. The Mosher's esters of each alcohol were determined to be >90% de. Reaction of (-)-22 with acryloyl chloride, followed by ring closing metathesis gave the dihydro-2-pyrone target (-)-5. Mitsunobu inversion of (+)-23 with p-nitrobenzoic acid, hydrolysis, and esterification with acryloyl chloride and ring closing metathesis gave pseudoenantiomeric segment (+)-6.
Total synthesis of (+)-phorboxazole A exploiting the Petasis-Ferrier rearrangement
Smith III,Minbiole,Verhoest,Schelhaas
, p. 10942 - 10953 (2007/10/03)
A highly convergent, stereocontrolled total synthesis of the potent antiproliferative agent (+)-phorboxazole A (1) has been achieved. Highlights of the synthesis include: modified Petasis-Ferrier rearrangements for assembly of both the C(11 - 15) and C(22-26) cis-tetrahydropyran rings; extension of the Julia olefination to the synthesis of enol ethers; the design, synthesis, and application of a novel bifunctional oxazole linchpin; and Stille coupling of a C(28) trimethyl stannane with a C(29) oxazole triflate. The longest linear sequence leading to (+)-phorboxazole A (1) was 27 steps, with an overall yield of 3%.
Phorboxazole synthetic studies. 1. Construction of a C(3-19) subtarget exploiting an extension of the Petasis-Ferrier rearrangement
Smith III, Amos B.,Verhoest, Patrick R.,Minbiole, Kevin P.,Lim, John J.
, p. 909 - 912 (2008/02/09)
(equation presented) In this, the first of two Letters, we outline our overall strategy for the total synthesis of phorboxazoles A (1) and B (2), rare oxazole-containing macrolides possessing extraordinary antimitotic activity, and describe the assembly o
