Asymmetric synthesis of (-)-(1R,7aS)-absouline

Journal article

The most efficient and concise asymmetric synthesis of (-)-(1R,7aS)- absouline to date, which was accomplished in eight steps and 20% overall yield from commercially available starting materials, is described. The doubly diastereoselective conjugate addition of lithium (S)-N-benzyl-N-(α- methylbenzyl)-amide to an enantiopure α,β-unsaturated ester derived from l-proline was employed as the key step. Subsequent hydrogenolytic N-debenzylation and acid-promoted cyclisation of the resultant β-amino ester produced the 1-aminopyrrolizidin-3-one scaffold, then reduction with DIBAL-H was followed by DCC-mediated coupling with (E)-p-methoxycinnamic acid to complete the synthesis of (-)-(1R,7aS)-absouline. © 2012 Elsevier Ltd. All rights reserved.

Authors: Davies, S; Fletcher, A; Lebee, C; Roberts, P; Thomson, J

• Publication status: Published
• Journal: TETRAHEDRON
• Volume: 69
• Issue: 4
• Pages: 1369-1377
• Publication date: 2013-01-28
• DOI: 10.1016/j.tet.2012.11.080
• EISSN: 1464-5416
• ISSN: 0040-4020
• Language: English
• Keywords: Asymmetric synthesis; Conjugate addition; Lithium amide; (-)-(1R,7aS)-Absouline