New synthetic long-chain tetraether derivatives, useful as components of liposomes for nucleic acid transfection

摘要

Synthetic long-chain tetraether derivatives (I) are new. Synthetic long-chain tetraether derivatives of formula (I) and their salts are new. g = 11-15, preferably 12-14; h = 13-17, preferably 14-16; R, R10, R11, R111 = H or Me; S1, S2 = tert-butyldimethylsilyl, tert-butyldiphenylsilyl, trityl, hydroxymethyl, tetrahydropyranyloxymethyl, benzyloxymethyl, or -A-(X1)r-B'-(X2)q-Y; A = CONR1, COO, CH2O, CH2OCO, CH2OCOO, CH2NR1CO, CH2OCONR1, CH2NR1COO, -CON((CH2)mY)-, CH2OCO(CH2)mO, CONH(CH2)mNHCO(CH2)mO, CH2COO, CH2O(PO2R1)O or CH2S; X1, X2 = 1-20C linear or branched alkylene or alkenylene, COC(R1)(Y)(CH2)m, (CH2)mNHCO, (CH2)mNHCOCH(Y), (CH2)mO(CH2)mNHCOCH(Y), ((CH2)mO)n, ((CH2)mO)nCO, (CH2)mNHCO(CH2)mCO, (CH2)m, (CH2)mCO, (CH2)mNH or (CH2)mNHCO(CH2)m; B' = ((CH2)mO)n, (O(CH2)m)n, (N(R1)COCHN(R1)2)o or (N(R6))p; Y = H, R2, N(R2)R3, N+R2R3R4, N((CH2)mY)2, NR2(CH2)mY, OR5, COR7, NHC(NH)NH2, NHCOY or SR8 (sic); R1, R6 = H, 1-12C linear, branched or cyclic alkyl, alkenyl, aralkyl or aryl, optionally substituted by at least one Y, or (CH2)mNHR2; R2-R5, R7, R8 = R1, (C=N+H2)NH2 or a ligand (bound to the lipid through a spacer); m = 1-5; n = 0-150; o = 0-10; p, r = 0-1; and q = 0-5. Independent claims are also included for: (1) preparation of (I); and (2) intermediates of formula (II). grp = tosylate, triflate, OH, phenoxy, benzyloxy, bromomagnesium, I, Br or Cl.