【结 构 式】 |
【分子编号】65212 【品名】 【CA登记号】 |
【 分 子 式 】C40H48F18N8O6 【 分 子 量 】1078.8426976 【元素组成】C 44.53% H 4.48% F 31.7% N 10.39% O 8.9% |
合成路线1
该中间体在本合成路线中的序号:(VIII)The macrocyclic tetraamine cyclam (I) is protected with p-toluenesulfonyl chloride at a 1:2 molar ratio, yielding the target tritosyl derivative (II) along with di- and monotosylated derivatives, which can be separated by fractional crystallization from MeOH (1). Subsequent condensation of (II) with α,α’-p-dibromoxylene (IIIa) gives the hexatosyl bis-cyclam (IV), which is finally deprotected by treatment with hot concentrated H2SO4 or with HBr in AcOH (1, 2). Alternatively, protection of (I) with di-tert-butyl dicarbonate provides the tri-Boc derivative (V), which is dimerized to (VI) by treatment with p-dibromoxylene (IIIa) and Na2CO3. Deprotection of (VI) is then effected by heating with aqueous HCl (3, 4). Similarly, treat-ment of the macrocyclic amine (I) with an excess of ethyl trifluoroacetate in the presence of Et 3N affords the tris-tri-fluoroacetyl cyclam (VII) as the major product. Subsequent condensation of (VII) with either p-dibro-moxylene (IIIa) or p-dichloroxylene (IIIb) in the presence of KI gives the trifluoroacetyl-protected compound (VIII), which is finally deprotected by treatment with NaOH or K2CO3 in MeOH (5, 6). Scheme 1.
【1】 Ciampolini, M., Fabbrizzi, L., Perotti, A., Poggi, A., Seghi, B., Zanobini, F. Dinickel and dicopper complexes with N,N-linked bis(cyclam) ligands. An ideal system for the investigation of electrostatic effects on the redox behavior of pairs of metal ions. Inorg Chem 1987, 26(21): 3527-33. |
【2】 Bridger, G.J., Skerlj, R.T., Thornton, D. et al. Synthesis and structure-activity relationships of phenylenebis(methylene)-linked bis-tetraazamacrocycles that inhibit HIV replication. Effects of macrocyclic ring size and substituents on the aromatic linker. J Med Chem 1995, 38(2): 366-78. |
【3】 Brandès, S., Gros, C., Denat, F., Pullumbi, P., Guilard, R. New facile and convenient synthesis of bispolyazamacrocyles using Boc protection. Determination of geometric parameters of dinuclear copper(II) complexes using ESR spectroscopy and molecular mechanics calculations. Bull Soc Chim Fr 1996, 133(1): 65-73. |
【4】 Dessolin, J., Galea, P., Vlieghe, P., Chermann, J.-C., Kraus, J.-L. New bicyclam-AZT conjugates: Design, synthesis, anti-HIV evaluation, and their interction with CXCR-4 coreceptor. J Med Chem 1999, 42(2): 229-41. |
【5】 Giandomenico, C.M., Yang, W. (AnorMED, Inc.). Process for preparation of N-1 protected N ring nitrogen containing cyclic polyamines and products thereof. WO 0226721. |
【6】 Yan, W., Giandomenico, C.M., Sartori, M., Moore, D.A. Facile N-1 protection of cyclam, cyclen and 1,4,7-triazacyclonanene. Tetrahedron Lett 2003, 44: 2481-3. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(IIIa) | 18697 | 1,4-bis(bromomethyl)benzene | 623-24-5 | C8H8Br2 | 详情 | 详情 |
(IIIb) | 55918 | 1,4-Bis(chloromethyl)benzene; alpha,alpha'-Dichloro-p-xylene; p-Xylylene dichloride | 623-25-6 | C8H8Cl2 | 详情 | 详情 |
(I) | 25362 | 1,4,8,11-Tetraazacyclotetradecane | 295-37-4 | C10H24N4 | 详情 | 详情 |
(II) | 65208 | C31H42N4O6S3 | 详情 | 详情 | ||
(IV) | 65209 | C70H90N8O12S6 | 详情 | 详情 | ||
(V) | 25363 | tri(tert-butyl) 1,4,8,11-tetraazacyclotetradecane-1,4,8-tricarboxylate | C25H48N4O6 | 详情 | 详情 | |
(VI) | 65210 | C58H102N8O12 | 详情 | 详情 | ||
(VII) | 65211 | C16H21F9N4O3 | 详情 | 详情 | ||
(VIII) | 65212 | C40H48F18N8O6 | 详情 | 详情 |