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Synlett 2004(5): 0823-0826  
DOI: 10.1055/s-2004-820033
LETTER
© Georg Thieme Verlag Stuttgart · New York

1,2-Ethylene-3,3-bis(4′,4′′-dimethoxytrityl Chloride) (E-DMT): Synthesis and Applications of a Novel Protecting Reagent

Natsuhisa Okaa, Yogesh S. Sanghvi*b, Emmanuel A. Theodorakisa
a Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, USA
b Rasayan Inc., 2802 Crystal Ridge Road, Encinitas, CA 92024-6615, USA
Fax: +1(760)9441543; e-Mail: rasayan@sbcglobal.net;
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Publication History

Received 5 January 2004
Publication Date:
10 March 2004 (online)

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Abstract

1,2-Ethylene-3,3-bis(4′,4′′-dimethoxytrityl chloride), (E-DMT) was developed as a novel, bifunctional protecting reagent. This new compound was found to have a potential as a multipurpose acid-labile protecting reagent which can afford a 5′,5′-tritylthymidine dimer and a unique 5′,3′-cyclic protected thymidine derivative in modest to good yields.

Key words

bis(trityl chloride) - bifunctional protecting reagent - acid-labile protecting group - solution-phase DNA synthesis - nucleo­side - thymidine

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Compound 3b was purchased from TCI (www.tciamerica.com).

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The purity of the complex can roughly be checked by the color of the complex and/or the solution of it since the green color of Co(I)Cl(PPh3)3 is changed into blue color of Co(II) species generated by degradation.

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Experimental for Synthesis of 2: Ethyl ester 4a (1.96 g, 6.0 mmol) was dried by repeated coevaporations with dry toluene and dissolved in dry THF (30 mL) under argon. Freshly prepared 1 M p-anisyl magnesium bromide solution in dry THF was added drop wise to the mixture under reflux and stirred for 30 min. The mixture was cooled to r.t., diluted with Et2O (150 mL), and washed with sat. NH4Cl aq solution (150 mL). The aqueous layer was back-extracted with Et2O (2 × 150 mL). The combined organic layers were washed with sat. NaCl aq solution (150 mL), dried over MgSO4, filtered, and concentrated to dryness. The residue was dried by repeated coevaporations with dry toluene and dissolved in AcCl (3 mL). The mixture was heated under reflux for 1.5 h, and then cooled to r.t. The mixture was added to cyclohexane (30 mL), stirred for 5 min, and kept at 4 °C for 20 h. The mixture was warmed to r.t. and the resultant precipitate was collected by suction filtration. The collected solid was washed with dry cyclohexane (5 × 3 mL) and dried under vacuum to afford 2 (2.97 g, 4.22 mmol, 70%) as an orange powder. 1H NMR (400 MHz, CDCl3): δ = 7.16-7.11 (m, 4 H), 7.08 (d, J = 8.8 Hz, 8 H), 7.01 (d, J = 7.6 Hz, 2 H), 6.94 (d, J = 8.8 Hz, 2 H), 6.78 (d, J = 8.8 Hz, 8 H), 3.80 (s, 12 H), 2.86 (s, 4 H). 13C NMR (100 MHz, CDCl3): δ = 158.7, 145.4, 140.6, 137.6, 130.9, 129.9, 127.9, 127.3, 127.1, 112.8, 82.5, 55.3, 37.5. ESI-MS: m/z for C44H41Cl2O4 (M + H+) 703. Anal. Calcd. for C44H40Cl2O4: C, 75.10; H, 5.73; Cl, 10.08. Found: C, 74.68; H, 6.07; Cl, 9.51.

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Analytical data for 7: 1H NMR (400 MHz, DMSO-d 6): δ = 11.3 (brs, 2 H), 7.50 (s, 2 H), 7.19-7.14 (m, 14 H), 6.94-6.93 (m, 2 H), 6.85-6.82 (m, 8 H), 6.20 (dd, J = 6.7, 6.7 Hz, 2 H), 5.32 (d, J = 4.4 Hz, 2 H), 4.33 (m, 2 H), 3.84 (m, 2 H), 3.71 (s, 12 H), 3.12 (m, 4 H), 2.72 (s, 4 H), 2.24 (ddd, J = 13.5, 6.7, 6.7 Hz, 2 H), 2.15 (ddd, J = 13.5, 6.7, 3.2 Hz, 2 H), 1.38 (s, 6 H). 13C NMR (100 MHz, DMSO-d 6): δ = 163.4, 157.8, 157.8, 150.1, 143.8, 140.4, 135.6, 135.4, 135.2, 129.5, 129.3, 127.8, 127.6, 126.7, 125.3, 113.0, 109.4, 85.7, 85.4, 83.6, 79.1, 70.5, 63.6, 55.0, 37.1, 11.7. HRMS: calcd for C64H65N4Na2O14 + (M - H+ +2 Na+) 1159.4287; found: 1159.4342.

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Analytical data for 8: 1H NMR (400 MHz, CDCl3): δ = 8.04 (brs, 1 H), 7.54 (s, 1 H), 7.37-6.69 (m, 24 H), 6.56 (dd, J = 9.2, 5.2 Hz, 1 H), 4.34 (m, 1 H), 4.04 (m, 1 H), 3.80 (s, 3 H), 3.78 (s, 3 H), 3.76 (s, 3 H), 3.72 (s, 3 H), 3.15-2.57 (m, 6 H), 2.27 (dd, J = 10.8, 3.2 Hz, 1 H), 2.11 (m, 1 H), 1.41 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 163.3, 158.6, 158.2, 158.1, 157.8, 150.0, 141.6, 141.5, 140.5, 140.1, 139.8, 138.5, 136.9, 135.6, 133.9, 130.9, 130.8, 129.4, 129.3, 129.3, 128.2, 127.7, 127.7, 127.6, 127.4, 127.3, 127.1, 113.2, 113.1, 113.0, 112.9, 110.8, 87.6, 86.6, 86.2, 85.5, 75.5, 55.3, 55.3, 55.3, 55.2, 40.4, 37.6, 36.8, 11.8. HRMS: calcd for C54H53N2O9 (M + H+) 873.3745; found: 873.3732.

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E-DMT is commercially available from Sai Dru Syn Laboratories, Hyderabad, India (www.saiintgroup.com).