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Synlett 2012; 23(15): 2251-2254
DOI: 10.1055/s-0031-1290457
letter
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Synthesis of Cryptopleurine and Boehmeriasin A via ­Organocatalytic Intramolecular Aza-Michael Addition

Chuanqi Zeng
State Key Lab of Analytical Chemistry for Life Science and Institute of Chemical Biology and Drug Innovation, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing, 210093, P. R. of China, Fax: +86(25)83317761   eMail: yushouyun@nju.edu.cn
,
Hanbin Liu
State Key Lab of Analytical Chemistry for Life Science and Institute of Chemical Biology and Drug Innovation, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing, 210093, P. R. of China, Fax: +86(25)83317761   eMail: yushouyun@nju.edu.cn
,
Mengyao Zhang
State Key Lab of Analytical Chemistry for Life Science and Institute of Chemical Biology and Drug Innovation, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing, 210093, P. R. of China, Fax: +86(25)83317761   eMail: yushouyun@nju.edu.cn
,
Jiajia Guo
State Key Lab of Analytical Chemistry for Life Science and Institute of Chemical Biology and Drug Innovation, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing, 210093, P. R. of China, Fax: +86(25)83317761   eMail: yushouyun@nju.edu.cn
,
Shunchao Jiang
State Key Lab of Analytical Chemistry for Life Science and Institute of Chemical Biology and Drug Innovation, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing, 210093, P. R. of China, Fax: +86(25)83317761   eMail: yushouyun@nju.edu.cn
,
Shouyun Yu*
State Key Lab of Analytical Chemistry for Life Science and Institute of Chemical Biology and Drug Innovation, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing, 210093, P. R. of China, Fax: +86(25)83317761   eMail: yushouyun@nju.edu.cn
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Publikationsverlauf

Received: 05. Juni 2012

Accepted after revision: 27. Juni 2012

Publikationsdatum:
14. August 2012 (online)

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Abstract

The enantioselective synthesis of phenanthroquinolizidine alkaloids cryptopleurine and boehmeriasin A was achieved in eight steps from commercial available Cbz-protected 2-piperidinone in 22% and 20% overall yield, respectively. The key steps of this route are intramolecular enantioselective aza-Michael addition, intramolecular aldol addition, and oxidative coupling.

Key words

alkaloids - enantioselectivity - ketones - Michael addition - total synthesis

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes


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  • 12 The Physical Data of the Synthetic (R)-Cryptopleurine (1a) [α]D 20 –78.8 (c 0.5, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.88 (s, 2 H), 7.77 (d, J = 9.0 Hz, 1 H), 7.22–7.14 (m, 2 H), 4.42 (d, J = 15.6 Hz, 1 H), 4.09 (s, 3 H), 4.05 (s, 3 H), 4.00 (s, 3 H), 3.61 (d, J = 15.6 Hz, 1 H), 3.27 (d, J = 10.8 Hz, 1 H), 3.05 (d, J = 16.3 Hz, 1 H), 2.97–2.78 (m, 1 H), 2.53–2.16 (m, 2 H), 2.10–2.02 (m, 1 H), 1.94–1.69 (m, 2 H), 1.67–1.32 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 157.4, 149.4, 148.3, 130.1, 126.4, 125.2, 124.3, 124.0, 123.5, 123.4, 114.8, 104.7, 103.8, 57.5, 56.13, 56.0, 55.9, 55.7, 55.5, 34.4, 33.5, 25.7, 24.2. IR: νmax = 2930, 2915, 2910, 1700, 1683, 1610, 1511, 1470, 1466, 1455, 1450, 1440, 1435, 1417, 1405, 1270, 1255, 1231, 1188, 1177, 1152, 1130, 1124, 1101, 1072, 1041, 1022, 1012, 845, 833, 809, 783, 761, 634 cm–1. ESI-HRMS: m/z calcd for C24H28NO3 [M + H]+: 378.2069; found: 378.2087.
  • 13 The Physical Data of the Synthetic (R)-Boehmeriasin A (1b) [α]D 27 –66.1 (c 0.15, MeOH). 1H NMR (400 MHz, CDCl3): δ = 7.95–7.84 (m, 3 H), 7.20 (dd, J = 9.0, 2.5 Hz, 1 H), 7.10 (s, 1 H), 4.34 (d, J = 15.3 Hz, 1 H), 4.09 (s, 3 H), 4.04 (s, 3 H), 4.00 (s, 3 H), 3.61 (d, J = 14.8 Hz, 1 H), 3.29 (d, J = 11.1 Hz, 1 H), 3.16 (dd, J = 16.7, 3.1 Hz, 1 H), 2.98–2.91 (m, 1 H), 2.44–2.24 (m, 2 H), 2.06–1.96 (m, 1 H), 1.92–1.71 (m, 3 H), 1.60–1.36 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 157.6, 149.4, 148.2, 130.3, 125.8, 125.1, 125.01, 124.9, 123.3, 114.8, 104.6, 104.0, 103.0, 57.5, 56.3, 56.98, 55.96, 55.5, 34.4, 33.5, 25.8, 24.2. IR: νmax = 2916, 1670, 1604, 1514, 1501, 1470, 1448, 1415, 1410, 1372, 1274, 1256, 1232, 1169, 1138, 1133, 1124, 1098, 1093, 1070, 1035, 1013, 999, 966, 941, 904, 844, 805, 796, 785, 760, 735 cm–1. ESI-HRMS: m/z calcd for C24H28NO3 [M + H]+: 378.2069; found: 378.2131.