A Highly Efficient Approach for the Synthesis of Cationic Lipid DOSPA

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

References and Notes

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17

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⁺].