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Synlett 2006(14): 2284-2286  
DOI: 10.1055/s-2006-949636
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Highly Efficient Approach for the Synthesis of Cationic Lipid DOSPA

Yanhong Lia, Robert J. Debsb, Timothy D. Heath*b
a School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, Wisconsin, 53705-2221, USA
b California Pacific Medical Center Research Institute, 475 Brannan St, Suite 220, San Francisco, CA 94107, USA
Fax: +1(608)2625345; e-Mail: tdheath@pharmacy.wisc.edu;
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Publication History

Received 23 February 2006
Publication Date:
24 August 2006 (online)

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Abstract

A highly efficient strategy has been developed for the synthesis of the cationic lipid, N-[2-({2,5-bis[(3-aminopropyl)amino]-1-oxopentyl}amino)ethyl]-N,N-dimethyl-2,3-bis[(1-oxo-9-octadecenyl)oxy] salt with hydrogen chloride (DOSPA). It involves the linkage of a cationic head group and a hydrophobic moiety in the presence of the standard coupling reagents.

Key words

cationic lipids - DNA - synthesis - liposome - transfection

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Selected Data for Compound 4.
1H NMR (400 MHz, CDCl3): δ = 5.43 (m, 4 H CHCH), 4.11-3.89 (m, 7 H, OCH, OCH2), 3.59 (s, 6 H, 2 CH3), 3.51 (m, 6 H, NCH2CHO, NCH2), 2.00 (m, 8 H, CH2CHCH), 1.46-1.20 (m, 48 H, CH2), 0.93 (t, 6 H, J = 5.2 Hz, CH3). 13C NMR (100 MHz, CDCl3): δ = 130.9, 129.7 (CHCH), 74.6 (CHO), 72.1, 69.5, 68.2 (CH2O), 65.8, 62.4 (CH2NCH2), 53.9, 53.5 (CH3), 43.1 (CH2NCO), 32.8-22.8 (CH2CH2), 14.3 (CH3). MALDI-MS: m/z = 664.6765 [M + H+].
Selected Data for Compound 10.
1H NMR (400 MHz, CD3OD): δ = 5.38 (m, 4 H, CHCH), 3.92-3.02 (m, 30 H, CHCONH, NCH3, CH2O, CHO, CH2N), 2.06-1.20 (m, 70 H, CH2, CH3, CH2CH2NH2, CH2CH2NH, CH2CHCO). 13C NMR (100 MHz, CDCl3): δ = 155.2 (CO), 130.1, 129.9 (CHCH), 80.6, 79.8, 78.9, 78.5 [C(CH3)3], 72.9 (CHO), 72.8, 71.2 (CH2NCH2), 68.7, 68.0 (OCH2), 60.9 (NCHCONH), 53.9, 52.8 (NCH3), 52.1 (CONHCH2CH2), 47.8-38.2 (CH2NCO), 32.1-22.1 (CH2CH2, CH2CH2NHCO, CH2CHCO), 14.3 (CH3). MALDI-MS: m/z = 1072.1552 [M + H+].