Synlett 2004(4): 729-731  
DOI: 10.1055/s-2004-817763
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Short Enantioselective Synthesis of Protected l-3-Hydroxy-4-methoxy-5-methyl Phenylalanine and its Corresponding Aldehyde - A Common Subunit of Ecteinascidin-743, Safracin and Congeners

Michaël De Paolis, Xiaochuan Chen, Jieping Zhu*
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France
Fax: +33(1)69077247; e-Mail: Zhu@icsn.cnrs-gif.fr;
Further Information

Publication History

Received 13 November 2003
Publication Date:
10 February 2004 (online)

Abstract

An asymmetric synthesis of appropriately protected l-3-hydroxy-4-methoxy-5-methyl phenylalanine from 3-methyl-catechol is described featuring a key enantioselective alkylation step.

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Compound 6. [α]D 23 +13 (c = 0.8, CHCl3). IR (CHCl3): 3382, 3034, 2981, 2938, 1725, 1598, 1495, 1370, 1293, 1218, 1178 cm-1. 1H NMR (250 MHz, CDCl3, 293 K): δ = 7.76 (d, J = 7.6 Hz, 2 H), 7.32 (d, J = 7.5 Hz, 2 H), 6.90 (br s, 1 H), 6.79 (br s, 1 H), 3.67 (s, 3 H), 3.48 (dd, J = 7.3, 5.5 Hz, 1 H), 2.88 (dd, J = 13.7, 5.5 Hz, 1 H), 2.67 (dd, J = 13.7, 7.3 Hz, 1 H), 2.44 (s, 3 H), 2.19 (s, 3 H), 1.42 (s, 9 H). 13C NMR (75 MHz, CDCl3, 293 K): 174.0, 149.3, 145.1, 142.2, 133.1, 132.8, 130.4, 129.5, 129.2, 128.5, 128.4, 121.8, 81.2, 60.5, 56.0, 40.2, 28.1, 27.9, 21.6, 15.9. MS (ESI+): m/z = 436.2 [M + H]+, 458.3 [M + Na]+, 474.2 [M + K]+. HRMS (ESI+): m/z [M + H+] calcd for C22H30O6S: 436.1794; found: 436.1789.
Compound 7. [α]D 23 +22 (c = 1, CHCl3). IR (CHCl3): 3426, 3024, 2933, 2830, 1716, 1590, 1496, 1343, 1232, 1087, 1007 cm-1. 1H NMR (300 MHz, CDCl3, 293 K): 9.52 (s, 1 H), 6.56 (m, 2 H), 5.96 (ddd, J = 17.7, 12.5, 7.2 Hz, 1 H), 5.82 (m, 1 H), 5.33 (ddt, J = 16.8, 1.7, 1.6 Hz, 1 H), 5.17 (m, 4 H), 4.47 (m, 4 H), 4.46 (m, 1 H), 3.80 (s, 3 H), 2.98 (dd, J = 14.0, 6.5 Hz, 1 H), 2.89 (dd, J = 14.0, 6.8 Hz, 1 H), 2.21 (s, 3 H). 13C NMR (75 MHz, CDCl3, 293 K): 199.2, 155.8, 151.6, 146.7, 133.2, 132.5, 132.3, 130.6, 123.8, 118.0, 117.5, 112.7, 69.4, 65.9, 60.9, 60.1, 35.2, 15.9. MS (ESI+): m/z = 334.2 [M + H]+.