Phorboxazole B synthetic studies: construction of C(1-32) and C(33-46) subtargets.
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 and 2-silyloxydiene 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.
Paterson
Ian
I
University Chemical Laboratory, Lensfield Road, Cambridge, UKCB2 1EW. ip100@cam.ac.uk.
Steven
Alan
A
Luckhurst
Chris A
CA
D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D047028:Macrocyclic Compounds / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis*
D006576:Heterocyclic Compounds, 4 or More Rings; D047028:Macrocyclic Compounds; D010080:Oxazoles; C408887:phorboxazole A