Reaction SMILES: [CH3:1][O:2][C:3]1[C:32]([O:33][CH3:34])=[CH:31][CH:30]=[CH:29][C:4]=1[C:5]([N:7]([C:17](=[O:28])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:19]=1[O:26][CH3:27])[CH2:8][CH2:9][CH2:10][CH2:11][NH:12][CH2:13][CH2:14][CH2:15][NH2:16])=[O:6].[NH2:35][CH:36]([C:40](O)=O)[CH:37]([CH3:39])[OH:38].[CH2:43](N(CC)CC)[CH3:44].C[N:51]([CH3:54])C=O>O1CCCC1.C(#N)C.O1CCOCC1>[CH:36]1([N:35]=[C:54]=[N:51][CH:18]2[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]2)[CH2:40][CH2:44][CH2:43][CH2:39][CH2:37]1.[OH:38][N:7]1[C:20](=[O:24])[CH2:19][CH2:18][C:17]1=[O:28].[CH3:1][O:2][C:3]1[C:32]([O:33][CH3:34])=[CH:31][CH:30]=[CH:29][C:4]=1[C:5]([N:7]([C:17](=[O:28])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:19]=1[O:26][CH3:27])[CH2:8][CH2:9][CH2:10][CH2:11][NH:12][CH2:13][CH2:14][CH2:15][NH2:16])=[O:6]
Reactant: CCN(CC)CC
Reactant: CC(O)C(N)C(=O)O
Reactant: CN(C)C=O
Agent: COc1cccc(C(=O)N(CCCCNCCCN)C(=O)c2cccc(OC)c2OC)c1OC
Solvent: C1COCCO1
Solvent: CC#N
Solvent: C1CCOC1
Product: C(=NC1CCCCC1)=NC1CCCCC1
Product: O=C1CCC(=O)N1O

Procedure:
The synthesis begins with N,N-bis(2,3-dimethoxybenzoyl)spermidine, a versatile reagent for the generation of spermidine catecholamides. The reagent may be prepared according to the method of [Bergeron et al, J. Org. Chem., 46, p. 4524 (1981)]. This compound is preferably coupled with N-carbobenzoxy-L-, D- or DL-threonine via the N-hydroxysuccinimide ester. Although the carbobenzoxy group is preferred, it will be understood that any suitable nitrogen protective group may be employed, e.g., t-butoxycarbonyl-, etc. The reagent is reacted with N-carbobenzoxy-L-, D- or DL-threonine and the condensing reagents dicyclohexylcarbodiimide and N-hydroxysuccinimide, optionally in the presence of a catalyst, such as a tertiary amine, e.g., triethylamine in an inert solvent, e.g, dimethylformamide, dioxane, acetonitrile or tetrahydrofuran (0° C.) to produce the secondary N'-acylated product, N'-(N-carbobenzoxy-L-, D- or DL-threonyl)-N,N-bis(2,3-dimethoxybenzoyl)spermidine, in 90% isolated yield. The threonyl amide intermediate was easily purified by silica gel chromatography, eluting with 5% MeOH in EtOAc. The carbobenzoxy protecting group was next removed quantitatively by reduction, preferably by hydrogenolysis over PdCl2 in methanol/HCl for 24 hours, thereby producing N-L-, D- or DL-threonyl-N,N-bis(2,3-dimethoxybenzoyl)spermidine. The methanol was removed under vacuum, the residue dissolved in water and the aqueous mixture washed with chloroform. The water was removed under vacuum, the residue dissolved in chloroform and washed with aqueous sodium carbonate. The compound may be purified on silica gel. The most revealing 1H nmr features at 60 MHz in CDCl3 were the absence of the benzyl methylene at 4.82 δ and the simplicity of the aromatic region. The envelope of complex peaks extending from 6.62-7.70 δ in (1) corresponding to eleven aromatic protons was simplified to two signals, one at 6.70-7.10 δ (4H) and one at 7.28-7.66 δ (2H). The low field signal corresponds to the ortho protons of the 2,3-dimethoxybenzoxy groups and the high field signal to the meta and para protons. The methyl protecting groups of the intermediate ether were removed preferably in quantitative fashion by reacting the amide with BBr3 in CH2Cl2 at 0° C. for 6 hours. The product is hydrolyzed with methanol generating the free catechol, N'-L-, D- or DL-threonyl-N,N-bis(2,3-dihydroxybenzoyl)spermidine.HBr. The product was chromatographed on Sephadex LH-20, eluting with 20% ethanol in benzene. At 60 MHz the most outstanding 1H nmr feature was the absence of the --OCH3 signal at 3.56 δ.