First Asymmetric Synthesis of Piperidine Alkaloid (-)-Morusimic Acid D

De-Sheng Yu; Wei-Xuan Xu; Liang-Xian Liu; Pei-Qiang Huang

doi:10.1055/s-2008-1072737

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Synlett 2008(8): 1189-1192
DOI: 10.1055/s-2008-1072737

LETTER

First Asymmetric Synthesis of Piperidine Alkaloid (-)-Morusimic Acid D

De-Sheng Yu^a, Wei-Xuan Xu^a, Liang-Xian Liu^a, Pei-Qiang Huang*^a,b
^a Department of Chemistry and Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. of China
Fax: +86(592)2186400; e-Mail: pqhuang@xmu.edu.cn;
^b The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. of China

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Publication History

Received 4 January 2008
Publication Date:
16 April 2008 (online)

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Abstract

The first asymmetric synthesis of (-)-morusimic acid D, a 2,3-trans-2,6-cis-2-methyl-6-substituted piperidin-3-ol containing alkaloid is reported. The key steps are the reductive alkylation of N,O-diprotected 3-hydroxyglutarimide, a stepwise reductive alkylation, and an asymmetric aldol-type reaction using a modified Evans chiral auxiliary.

Key words

asymmetric synthesis - N-acyliminium ions - imides - aldol reaction - piperidines - alkaloids - morusimic acid D

References and Notes

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27

All new compounds gave satisfactory analytical and spectral data. Selected physical and spectral data for morusimic acid D methyl ester (22): pale yellow powder; mp 132-135 °C; [α]_D ²⁰ -11.3 (c 0.4, CHCl₃). IR (film): 3387, 2929, 2854, 1731, 1438, 1380, 1305, 1165, 1061 cm^-1. ¹H NMR (400 MHz, CD₃OD): δ = 1.40 (s, 3 H), 1.22-1.68 (m, 20 H), 2.09 (m, 2 H), 2.30-2.50 (m, 2 H), 2.92 (m, 1 H), 3.08 (m, 1 H), 3.42 (s, 1 H), 3.64 (s, 3 H), 3.95 (m, 1 H). ¹³C NMR (100 MHz, CD₃OD): δ = 16.00, 26.52, 26.56, 28.33, 30.43, 30.48, 30.52, 30.56, 30.59, 32.92, 34.26, 38.05, 43.25, 52.15, 58.49, 59.24, 69.23, 70.70, 173.92. ESI-HRMS: m/z calcd for C₁₉H₃₈NO₄ [M + H]⁺: 344.2795; found: 344.2798.