Investigations of an annulation-fragmentation-spirocyclisation approach to fawcettimine-type Lycopodium alkaloids |
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| Institution: | 1. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy;2. Dipartimento di Scienze Biomediche Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Via C. Pascal 36, 20133 Milano, Italy;3. Dipartimento di Scienze Farmacologiche e Biomolecolari—DiSFeb, Università degli Studi di Milano, via C. Pascal 36, 20133 Milano, Italy;4. Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy;1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People’s Republic of China;2. University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China;3. School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, People’s Republic of China;1. School of Chemistry and Molecular Bioscience, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia;2. School of Natural Sciences (Chemistry), College of Sciences and Engineering, University of Tasmania, Private Bag 75, Hobart, TAS 7001, Australia;1. Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan;2. Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan |
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| Abstract: | This paper reports progress in the development of a furan oxidative N-spirocyclisation approach to the fawcettimine alkaloids huperzine Q and lycopladine D. A short synthesis is described of a key intermediate cyclopentaindolizidine that subsequently fragments by N-acylation and β-elimination. The stereochemistry of 1,4-addition of cyanide to the resulting enone is discussed with supporting molecular modelling calculations. N-Deprotection is shown to be accompanied by cyclisation onto the nitrile group, resulting in a tricyclic lactam with a twisted amide functionality. Elaboration of this lactam afforded four of the five rings present in lycopladine D with just the C(8) carbon lacking. |
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| Keywords: | Alkaloids Enamines Transannular reactions Spirocycles Medium-bridged lactams |
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