title: Stereocomplementary routes to hydroxylated nitrogen heterocycles: total syntheses of casuarine, australine, and 7-epi-australine.
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 N-O 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 C-C 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 C-O double bond is independent of the ring size, occurring preferentially from the top face either in a six- or five-membered ring.
authors.affiliation: Department of Chemistry Ugo Schiff, associated with ICCOM-CNR, University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Parmeggiani
authors.forename: Francesca
authors.initials: F
authors.lastname: Cardona
authors.forename: Leonardo
authors.initials: L
authors.lastname: Giusti
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Reissig
authors.forename: Andrea
authors.initials: A
authors.lastname: Goti
mesh_terms: D000466:Alkadienes / Q000737:chemistry; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry*; D010084:Oxidation-Reduction; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000466:Alkadienes; D000470:Alkaloids; D006571:Heterocyclic Compounds; D011758:Pyrroles; D011759:Pyrrolidines; D011763:Pyrrolizidine Alkaloids; C409108:casuarine; C059794:australine; C025947:propadiene; C032519:pyrrolidine; D009584:Nitrogen
keywords: alkaloids; allenes; nitrones; nucleophilic attack; stereoselectivity