Ulapualides 4- oxazoles

Several nitrogen-containing macrolides were reported to be obtained from marine sources. Ulapualides A (254) and B (255), possessing unique structures with three contiguous oxazoles, were isolated from the egg... 

C-NMR data for some of the more complex and/or recently discovered alkaloids have been reported (Table III). The structure of the trisoxazole portion of ulapualide B (63) was elucidated largely by analysis of fully coupled and partially decoupled 13 C-NMR spectra. A series of simple oxazoles has been subjected to systematic analysis by 13 C-NMR spectroscopy and provides useful models (125). 

A new synthesis of (-)-ulapualide A was completed by the group of Pattenden following a previous synthesis of a different diastereisomer whose chiroptical and H NMR spectroscopic data were identical with those of the natural product <07 AG(E)4359>. The first synthesis of siphonazole 119 was completed. Both the oxazole rings were constructed using rhodium carbene chemistry <07CC1508>. 

Chattopadhyay, S.K., and Pattenden, G., Towards a total synthesis of ulapualide A. A concise synthesis of the fm-oxazole macrolide core and entire carbon skeleton, Synlett, 1345, 1997. 

Panek and co-workersdescribed syntheses of suitably bis-functionalized tris-oxazoles as intermediates leading to kabiramide C, halichondramide, and ulapualide A based on sequential application of a modified Hantzsch condensation methodology (Scheme 1.395). For example, condensation of cinnamide with ethyl... 

Panek s group ° employed the Schlosser-Wittig olefination reaction of an in situ-generated tris-oxazole phosphonium salt to incorporate the trans double bond of an advanced intermediate leading to ulapualide A (Scheme 1.397). Model studies that precedent this work were described in Scheme 1.298. Thus reaction of 1560 with 1561 in the presence of excess triethylphosphine and one equivalent of LDA generated 1562 in excellent yield as a single double-bond isomer. This result was noteworthy in that it demonstrated the viability of this type of bond construction in the presence of a potentially labile p-alkoxy substituent. 

Pattenden and co-workers " proposed a convergent alternative strategy to the ulapualide core, wherein suitably functionalized monooxazoles would be coupled first. Construction of the final, central oxazole ring would then complete the macrocyclization process. 

Subsequently, Kempson and Pattenden " applied this strategy to prepare a model for the complete tris-oxazole macrolide core of ulapualides (Scheme 1.402). 

Pattenden, G., Ashweek, N.J., Baker-Glenn, C.A.G., Kempson, J., Walker, G.M., and Yee, J.G.K (2008) Total synthesis of (-)-ulapualide A, a novel tris-oxazole macrolide from marine nudibranchs, based on some biosynthesis speculation. Org. Biomol. Chem., 6,1478-1497. 

Knight, D.W., Pattenden, G., and Rippon, D.E. (1990) Synthesis of the tris-oxazole ring system of ulapualides. Synlett, 36-37. 

Chattopadhyay, S.K. and Pattenden, G. (1995) Synthetic studies towards novel tris-oxazole based macrolides of marine origin. Stereocontrolled synthesis of the C20-C35 fragment in ulapualide A. Tetrahedron Lett., 36, 5271-5274. 

Panek, J.S. and Beresis, R.T. (1996) Studies directed toward the synthesis of ulapualide A. Asymmetric synthesis of the C8-C25 tris-oxazole fragment/. Org. Chem., 61, 6496-6497. 

Chattopadhyay, S.K. and Pattenden, G. (2000) A total synthesis of the unique tris-oxazole macrolide ulapualide A produced by the marine nudibranch Hexabranchus sanguineus. J. Chem. Soc. Perkin Trans. I. 2429-2454. 

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