Diastereoselective synthesis of new polyhydroxylated indolizidines from ( l)-glutamic acid

• Published in: Tetrahedron Vol. 61; no. 20; pp. 4743 - 4754
• Main Authors: Kadlečíková, Katarína, Dalla, Vincent, Marchalín, Štefan, Decroix, Bernard, Baran, Peter
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.05.2005
• Subjects: Amino acid; Chiral pool; Diastereoselective synthesis; Swainsonine's and Lentiginosine's analogues; Diastereoselective synthesis; Amino acid; Chiral pool; Swainsonine's and Lentiginosine's analogues
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2005.03.029

A diastereoselective synthesis of two new swainsonine's analogues 1a and 1b with the piperidine ring fused to a phenyl nucleus at C6-C7, namely (1 R, 2 S, 10 R, 10a R)-(+)-1,2,10-trihydroxy-1,2,3,5,10,10a-hexahydrobenzo[ f] indolizine ( 1a ) and (1 S, 2 R, 10 R, 10a R)-(+)-1,2,10-trihydroxy-1, 2, 3, 5, 10, 10a-hexahydrobenzo[ f] indolizine ( 1b ), is described. Throughout this work, the effectiveness of the tricyclic indolizidine dione 5 , readily available in three steps from the cheap l-glutamic acid, as an attractive platform for chemo- and stereodivergent transformations is illustrated. The key steps involved totally diastereoselective ketone reduction of compound 5 and catalytic cis-dihydroxylation of the unsaturated amide 10 . The synthetic strategy also allowed for the diastereoselective synthesis of benzoanalogues of the 1,8a-di- epi-lentiginosine 3a ((1 R, 2 S, 10a R)-(+)-1,2-dihydroxy-1, 2, 3, 5, 10, 10a-hexahydrobenzo[ f]indolizine) and 2,8a-di- epi-lentiginosine 3b ((1 S, 2 R, 10a R)-(+)-1,2-dihydroxy-1,2,3,5,10,10a-hexahydrobenzo[ f]indolizine). Graphical Abstract