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Synlett 2011(4): 565-568  
DOI: 10.1055/s-0030-1259521
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Studies towards the Total Asymmetric Synthesis of the Pentacyclic Indole Alkaloid Arboflorine: Asymmetric Synthesis of a Key Intermediate

Yu Dua, Hui-Ying Huangb, Hui Liua, Yuan-Ping Ruana, Pei-Qiang Huang*a
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 School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P. R. of China
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Publication History

Received 27 November 2010
Publication Date:
27 January 2011 (online)

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Abstract

The synthesis of a plausible key intermediate for a biomimetic asymmetric synthesis of indole alkaloid arboflorine is described. The method featured the use of Ellman’s sulfinamide chemistry for the establishment of the first chiral center, and the Polonovski-Potier reaction for the formation of the α-aminonitrile moiety.

Key words

indole alkaloids - biogenetic pathway - intermediate - Polonovski-Potier reaction - Ellman’s sulfinamide

18

All new compounds gave satisfactory analytical and spectral data.
Experimental Procedure for the Synthesis of the Key Intermediate 28: A solution of MCPBA (72%, 84 mg, 0.35 mmol) in CH2Cl2 (1 mL) was added dropwise to a solution of compound 25 (138 mg, 0.25 mmol) in CH2Cl2 (1.5 mL) at 0 ˚C. After stirring at 0 ˚C for 1 h, K2CO3 (70 mg, 0.5 mmol) was added. After stirring for an additional 1 h at 0 ˚C, the mixture was filtered through celite. The residue was purified by flash column chromatography on silica gel (R f 0.18, eluent: CH2Cl2-MeOH, 15:1) to give N-oxide 26 (140 mg, 98%), which was dissolved in anhyd CH2Cl2 (2.0 mL) and cooled to 0 ˚C. TFAA (0.07 mL, 0.5 mmol) was added. After being stirred for 30 min at 0 ˚C, an aqueous solution (0.5 mL) of KCN (65 mg, 1.0 mmol) was added, and the solution was buffered to pH 4 by addition of AcOH and NaOAc. After stirring for 1 h at 0 ˚C, the mixture was basified with K2CO3 and extracted with CH2Cl2 (3 × 3 mL). The combined extracts were successively washed with H2O (2 mL) and brine (1 mL), dried over anhyd Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on neutral Al2O3 (R f = 0.4, eluent: EtOAc-n-hexane, 1:4) to give compound 28 (108 mg, 74% from 25) as a white amorphous solid. IR (film): 3370, 2978, 2934, 2216 (w, CN), 1730 (s), 1511, 1458, 1392, 1367, 1328, 1248, 1169, 1133 cm-¹. ¹H NMR (400 MHz, CDCl3; diastereomeric mixture and rotamers): δ = 1.25 (m, 3 H, CH2CH 3), 1.33 (m, 3 H, CHCH 3), 1.44 [m, 9 H, C(CH3)3], 1.65 [s, 9 H, C(CH3)3], 2.08-2.18 (m, 1 H, C=CHCH 2), 2.26-2.44 (m, 1 H, C=CHCH 2), 2.53-2.63 (m, 1 H, C=CHCH2CH 2), 2.70-2.95 (m, 5 H, C=CHCH2CH 2, ArCH 2CH 2N), 4.03 (s, 2 H, CH2CO2), 4.16 (m, 2 H, CH 2CH3), 4.27 (s, 1 H, CHCN), 4.22-4.38 (m, 1 H, CHCH3), 4.57 (br s, 1 H, NH), 5.86, 5.89 (br s, 1 H, C=CH), 7.24 (t,

J = 7.3 Hz, 1 H, ArH), 7.29 (t, J = 7.3 Hz, 1 H, ArH), 7.53 (d, J = 7.8 Hz, 1 H, ArH), 8.09 (d, J = 7.8 Hz, 1 H, ArH). ¹³C NMR (100 MHz, CDCl3; diastereomeric mixture and rotamers): d = 14.2, 22.4, 22.5, 25.1, 25.2, 28.1, 28.25, 28.29, 28.33, 28.7, 29.6, 33.17, 33.2, 45.6, 45.65, 47.5, 52.4, 55.2, 55.3, 60.8, 79.8, 80.1, 84.0, 115.7, 115.9, 116.1, 118.0, 118.1, 118.2, 122.5, 124.2, 124.449, 124.458, 129.2, 129.7, 129.8, 134.08, 134.14, 135.8, 150.4, 155.3, 170.12, 170.18. HRMS: m/z [M + Na+] calcd for C32H44N4NaO6: 603.3159; found: 603.3153.