Synthesis of (±)‐Lasubine II Using N‐Methoxyamines

Abstract

The synthesis of (±)-lasubine II has been achieved through a three-component allylation capitalizing on the unique properties of N-methoxyamines. This reaction enabled the installation of all the carbon atoms of lasubine II in a single operation. The N-methoxy group was efficiently used for the subsequent nitrone formation. A single-step cyclization of isoxazolidines or N-methoxyamines to form functionalized piperidine rings was also developed.

Development of a Chiral N-Alkoxyamide Strategy and Application to the Asymmetric Total Synthesis of Fasicularin

“…1 H NMR (500 MHz, CDCl 3 ):  = 5.94 (ddd, J = 17.2, 10.6, 8. 6 Hz, 1 H), 5.60 (br, 1 H), 5.09 (dd, J = 10.6, 2.0 Hz, 1 H), 5.05 (ddd, J = 17.2, 2.0, 0.9 Hz, 1 H), 2.79 (d, J = 4.6 Hz, 3 H), 2.54 (br, 1 H), 2.34 (ddd, J = 15.2, 7.7, 7.7 Hz, 1 H), 2.24 (ddd, J = 15.2, 7.7, 6.9 Hz, 1 H), 2.00 (ddd, J = 14.6, 7.7, 7.7 Hz, 1 H), 1.95 (ddd, J = 11.5, 8.6, 3.7 Hz, 1 H), 1.75-1.67 (m, 2 H), 1.67-1.61 (m, 2 H), 1.61-1.50 (m, 2 H), 1.46 (ddddd, J = 13.2, 3.7, 3.7, 3.7, 0.9 Hz, 1 H), 1.30-1.23 (m, 1 H), 1.20 (ddd, J = 13.5, 12.0, 4.9 Hz, 1 H). 13…”

“…Hz, 2 H), 7.13 (d, J = 7 7. Hz, 2 H), 5.47 (q, J = 6 6. Hz, 1 H), 2.31 (s, 3 H), 1.70 (d, J = 6.6 Hz, 3 H).13 C NMR (125 MHz, CDCl 3 ):  = 164.0 (C), 138.9 (C), 136.1 (C), 134.4 (CH), 129.2 (CH), 129.0 (C), 127.7 (CH), 123.5 (CH), 85.1 (CH), 21.4 (CH 3 ), 20.6 (CH 3 ).…”

“…4 Our developed strategy has been successfully applied to the total synthesis of biologically active natural products such as gephyrotoxin 3b,5 and lasubine II. 6 In this article, we report the full details of our total synthesis of fasicularin (10, Scheme 1c). 7 We initially demonstrated a racemic total synthesis to confirm whether reactivity control by N-methoxyamide 2 was possible in the total synthesis (Scheme 1a).…”

Total Synthesis of Lycopodium Alkaloids Palhinine A and Palhinine D

“…Retrosynthetically, as shown in Scheme , palhinines A and D could be achieved through elaboration of formally unified synthon A , which might be envisaged from a common synthon C by its C3-OH configuration inversion involving a chemo- and stereoselective reduction of B . Strategically, the key nine-membered azonane ring in C could be generated by the reductive N–O cleavage in D , which would be logically envisioned from E via a selective intramolecular nitrone–alkene cycloaddition as a key step. , Chemically, the olefin moiety and hydroxylamine unit in E could be introduced by sequential transformations including Wittig reaction and oxime formation/reduction from functionalized isotwistane building block 2 , which is accessible from 1 on the basis of our early synthetic studies…”