296785-14-3Relevant academic research and scientific papers
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.
Asymmetric synthesis of phorboxazole B - Part I: Synthesis of the C20-C38 and C39-C46 subunits
Evans, David A.,Cee, Victor J.,Smith, Thomas E.,Fitch, Duke M.,Cho, Patricia S.
, p. 2533 - 2536 (2007/10/03)
The total synthesis of the antitumor marine macrolide phorboxazole B (1) has been realized. The phorboxazoles are representative of a new structural class of macrolides and are among the most cytostatic natural products known: inhibiting the growth of tum
Application of complex aldol reactions to the total synthesis of phorboxazole B
Evans,Fitch,Smith,Cee
, p. 10033 - 10046 (2007/10/03)
The synthesis of phorboxazole B has been accomplished in 27 linear steps and an overall yield of 12.6%. The absolute stereochemistry of the C4-C12, C33-C38, and C13-C19 fragments was established utilizing catalytic asymmetric aldol methodology, while the absolute stereochemistry of the C20-C32 fragment was derived from an auxiliary-based asymmetric aldol reaction. All remaining chirality was incorporated through internal asymmetric induction, with the exception of the C43 stereocenter which was derived from (R)-trityl glycidol. Key fragment couplings include a stereoselective double stereodifferentiating aldol reaction, a metalated oxazole alkylation, an oxazole-stabilized Wittig olefination, and a chelation-controlled addition of the fully elaborated alkenyl metal side chain.
