Asymmetric total synthesis of (-)-δ-lycorane

1H NMR

13C NMR

Org. Chem. Front., 2017, Advance Article
DOI: 10.1039/C7QO00021A, Research Article

Junliang Wang, Jianneng Li, Xianwang Shen, Cong Dong, Jun Lin, Kun Wei
A first asymmetric synthesis of (-)-δ-lycorane by using a chiral bifunctional squaramide-catalysed cascade reaction is reported.

Asymmetric total synthesis of (−)-δ-lycorane

Junliang Wang,ab   Jianneng Li,a   Xianwang Shen,a  Cong Dong,a   Jun Lin*ab and   Kun Wei*a  

*Corresponding authors

aSchool of Chemical Science and Technology, Yunnan University, P. R. China

bSchool of Chemical Science and Technology, Yunnan University, Key Laboratory of Medicinal Chemistry for Natural Resource (Ministry of Education), Kunming, P. R. China
E-mail: weikun@ynu.edu.cn, linjun@ynu.edu.cn
Fax: +86871 65031633
Tel: +86871 65031633

Org. Chem. Front., 2017, Advance Article

DOI: 10.1039/C7QO00021A

A first asymmetric synthesis of the lycorine-type Amaryllidaceae alkaloid (−)-δ-lycorane by using a chiral bifunctional squaramide-catalysed cascade reaction as a powerful tool to construct the skeleton of the alkaloid on the basis of unsaturated β-ketoester and nitroalkene is reported. The sequence afforded a highly functionalized intermediate with three stereogenic centres with high diastereoselectivity (>20:1 dr) and high enantioselectivity (92% ee) in one step, which was converted into (−)-δ-lycorane in eight steps.

The residue was purified by flash silica 8 Please do not adjust margins Please do not adjust margins Please do not adjust margins gel chromatography (DCM/MeOH = 10/1) to give (−)-δ-lycorane (9 mg, 72%) as a white solid.

m.p.: 125-126 °C; [α] = -51.9, (c = 0.1, CHCl3);

IR (thin film, ν cm -1): 3551, 3477, 3414 , 1637, 1617, 619, 473;

1H-NMR (500 MHz, CDCl3), δ (ppm): 6.79 (s, 1H), 6.68 (s, 1H), 5.93 (s, 2H), 4.29 (d, J = 14.5 Hz, 1H), 3.95 (dd, J = 11.0, 8.5 Hz, 1H), 3.68 (d, J = 14.5 Hz, 1H), 3.52 (dd, J = 11.5, 4.0 Hz, 1H), 3.25 (s, 1H), 2.50 (m, 1H), 2.41 (d, J = 2.0 Hz, 1H), 1.86 (m, 1H), 1.77 (m, 2H), 1.66 (d, J = 14.5 Hz, 1H), 1.59 (m, 2H), 1.37 (m, 2H);

13C-NMR (125 MHz, CDCl3) δ (ppm): 149.0, 146.5, 131.3, 120.5, 109.5, 106.9, 101.5, 66.3, 55.1, 50.7, 39.7, 34.5, 29.6, 29.0, 24.8, 20.4;

HRMS (ESI): m/z calcd for C16H20NO2 + [M + H]+ : 258.1489, found: 258.1488.

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