Stereocomplementary Routes to Hydroxylated Nitrogen Heterocycles: Total Syntheses of Casuarine, Australine, and 7-epi-Australine

Year: 2013

Authors: Parmeggiani C., Cardona, F., Giusti L., Reissig H.-U., Goti A.

Autors Affiliation: Department of Chemistry Ugo Schiff, ICCOM-CNR, University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy; Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany

Abstract: Addition of lithiated 1-benzyloxyallene to a D-arabinose-derived cyclic nitrone occurred with perfect diastereoselectivity furnishing a bicyclic 1,2-oxazine derivative, which is an excellent precursor for pyrrolizidine alkaloids hydroxylated at C-7 with optional configuration at this stereogenic center. Depending on the stage of the NO bond cleavage and ring re-closure, 7-hydroxypyrrolizidines with 7R or 7S configuration were obtained, as a result of completely selective addition reactions occurring complementarily at the bottom or top face of the endocyclic CC double bond in six- and five-membered B rings, respectively. Applicability of these stereodivergent routes to obtain polyhydroxy pyrrolizidine alkaloids is demonstrated by the efficient syntheses of casuarine and australine as examples of the two classes of diversely configured 7-hydroxypyrrolizidine alkaloids. An alternative synthesis of australine and two strategies for the preparation of 7-epi-australine are also reported, which demonstrate that the stereoselectivity of hydride reduction of an exocyclic CO double bond is independent of the ring size, occurring preferentially from the top face either in a six- or five-membered ring.


Volume: 19 (32)      Pages from: 10595  to: 10604

More Information: We thank MIUR-Italy (PRIN 2008, 200824M2HX, and PRIN 2010-2011, 2010L9SH3K 006) and Ente Cassa di Risparmio di Firenze (CRF, 2009/3141) for financial support. Support of the Berlin group by the Deutsche Forschungsgemeinschaft and Bayer HealthCare is most gratefully acknowledged. MIUR is also acknowledged for a doctoral grant to CP. The DAAD is gratefully acknowledged for a research fellowship to LG. We thank Dr. C. Bello, Universite de Lausanne, Switzerland, for the biological assays with glycosidases and Dr. R. Zimmer (Berlin) for his help during the stay of LG in Berlin and the preparation of the manuscript.
DOI: 10.1002/chem.201301320

Citations: 53
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