Design, iterative synthesis and structure of novel optically active trispiro-dendritic melamines incorporating ‘open-chain’ versus ‘closed-chain’ serinolic peripheral units

Starting from commercial C-2-substituted 2-aminopropane-1,3-diols (serinols, ‘open-chain’ peripheral units) and optically active amino-1,3-dioxanes (‘closed-chain’ peripheral units) as cycloacetals of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol (p-nitrophenylserinol) or its 2-dimethylamino analogue, we herein report a new series of di- and trimeric G-1 trispiro-dendritic melamines, they were synthesised convergently by iterative chemoselective amination of cyanuric chloride. Depending on the number of hydroxymethyl groups in the ‘open-chain’ peripheral unit and the type of the rigid amino-anchorage (axial or equatorial) of the ‘closed-chain’ counterpart, the classic restricted rotation about the C(s-triazine)–N(exocyclic) partial double bonds induced, progressively, specific spatial arrangements in angularly connected G-0 and G-1 dendrons, including axial chirality in G-1 dimeric or G-1 trimeric melamines.

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2-Chloro-4-{[(2R,4S,5S)-5-(dimethylamino)-4-(4-nitrophenyl)-1,3-dioxan]-2-yl}methylamino-6-[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino-s-triazineC26H29ClN8O8[α]D20 = +160.1 (c 0.5, DMSO)ee = 99% based on the starting materialsSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol and diastereoselective of (1S,2S)-2-dimethylamino-1-(4-nitrophenyl)propane-1,3-diol

1-{4-{[(2R,4S,5S)-5-(Dimethylamino)-4-(4-nitrophenyl)-1,3-dioxan]-2-yl}methylamino-6-[(4S,5S)-4-(4nitrophenyl)-1,3-dioxan-5-yl]amino-s-triazin-2-yl}-piperazineC30H38N10O8[α]D20 = +112.0 (c 0.5, DMSO)ee = 99% based on the starting materialsSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol and diastereoselective of (1S,2S)-2-dimethylamino-1-(4-nitrophenyl)propane-1,3-diol

2-Chloro-4,6-bis{4-{6-{[1,3-dihydroxy-2-(methyl)prop-2-yl]amino}-4-{[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino}-s-triazin-2-yl}-piperazin-1-yl}-s-triazineC45H58ClN19O12[α]D20 = +72.3 (c 0.5, DMSO)ee = 99% based on the starting materialSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol

2-Chloro-4,6-bis{4-{{[1-hydroxy-2-(hydroxymethyl)but-2-yl]amino}-4-{[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino}-s-triazin-2-yl}-piperazin-1-yl}-s-triazineC47H62ClN19O12[α]D20 = +89.5 (c 0.5, DMSO)ee = 99% based on the starting materialSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol

2-Chloro-4,6-bis{4-{6-{[1,3-dihydroxy-2-(hydroxymethyl)prop-2-yl]amino}-4-{[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino}-s-triazin-2-yl}-piperazin-1-yl}-s-triazineC45H58ClN19O14[α]D20 = +98.8 (c 0.5, DMSO)ee = 99% based on the starting materialSource of chirality: diastereoselective ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol

2-Chloro-4,6-bis{4-{{[1,3-dihydroxy-2-(methyl)prop-2-yl]amino}-4-{[(2R,4S,5S)-5-(dimethylamino)-4-(4-nitrophenyl)-1,3-dioxan-2-yl]methylamino}-s-triazin-2-yl}-piperazin-1-yl}-s-triazineC51H72ClN21O12[α]D20 = +184.5 (c 0.5, DMSO)ee = 99% based on the starting materialSource of chirality: diastereoselective ring closure of (1S,2S)-2-dimethylamino-1-(4-nitrophenyl)propane-1,3-diol

2-Chloro-4,6-bis{4-{{[1-hydroxy-2-(hydroxymethyl)but-2-yl]amino}-4-{[(2R,4S,5S)-5-(dimethylamino)-4-(4-nitrophenyl)-1,3-dioxan-2-yl]methylamino}-s-triazin-2-yl}-piperazin-1-yl}-s-triazineC53H76ClN21O12[α]D20 = +163.3 (c 0.5, DMSO)ee = 99% based on the starting materialSource of chirality: diastereoselective ring closure of (1S,2S)-2-dimethylamino-1-(4-nitrophenyl)propane-1,3-diol

2-Chloro-4,6-bis{4-{{[1,3-dihydroxy-2-(hydroxymethyl)prop-2-yl]amino}-4-{[(2R,4S,5S)-5-(dimethylamino)-4-(4-nitrophenyl)-1,3-dioxan-2-yl]methylamino}-s-triazin-2-yl}-piperazin-1-yl}-s-triazineC51H72ClN21O14[α]D20 = +183.3 (c 0.5, DMSO)ee = 99% based on the starting materialSource of chirality: diastereoselective ring closure of (1S,2S)-2-dimethylamino-1-(4-nitrophenyl)propane-1,3-diol

2-Chloro-4,6-bis{4-{4-{[(2R,4S,5S)-5-(dimethylamino)-4-(4-nitrophenyl)-1,3-dioxan]-2-yl}methylamino-6-[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino-s-triazin-2-yl}-piperazin-1-yl}-s-triazineC63H74ClN23O16[α]D20 = +128.5 (c 0.5, DMSO)ee = 99% based on the starting materialsSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol and diastereoselective of (1S,2S)-2-dimethylamino-1-(4-nitrophenyl)propane-1,3-diol

3-{4,6-Bis{4-{{[1,3-dihydroxy-2-(hydroxymethyl)prop-2-yl]amino}-4-{[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino}-s-triazin-2-yl}-piperazin-1-yl}-s-triazin-2-yl}-7,11,18,21-tetraoxa-3,15-diazatrispiro[5.2.2.5.2.2]heneicosaneC60H83N21O18[α]D20 = +75.1 (c 0.5, DMSO)ee = 99% based on the starting materialSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol

3-{4,6-Bis{4-{4-{[(2R,4S,5S)-5-(dimethylamino)-4-(4-nitrophenyl)-1,3-dioxan]-2-yl}methylamino-6-[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino-s-triazin-2-yl}-piperazin-1-yl}-s-triazin-2-yl}-7,11,18,21-tetraoxa-3,15-diazatrispiro[5.2.2.5.2.2]heneicosaneC78H99N25O20[α]D20 = +147.0 (c 0.5, DMSO)ee = 99% based on the starting materialsSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol and diastereoselective of (1S,2S)-2-dimethylamino-1-(4-nitrophenyl)propane-1,3-diol

3,15-Bis{4,6-bis{4-{6-{[1,3-dihydroxy-2-(methyl)prop-2-yl]amino}-4-{[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino}-s-triazin-2-yl}-piperazin-1-yl}-s-triazin2-yl}-7,11,18,21-tetraoxa-3,15-diazatrispiro[5.2.2.5.2.2]heneicosaneC105H140N40O28[α]D20 = +76.3 (c 0.5, DMSO)ee = 99% based on the starting materialSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol

3,15-Bis{4,6-bis{4-{6-{[1-hydroxy-2-(hydroxymethyl)but-2-yl]amino}-4-{[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino}-s-triazin-2-yl}-piperazin-1-yl}-s-triazin2-yl}-7,11,18,21-tetraoxa-3,15-diazatrispiro[5.2.2.5.2.2]heneicosaneC109H148N40O28[α]D20 = +79.4 (c 0.5, DMSO)ee = 99% based on the starting materialSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol

3,15-Bis{4,6-bis{4-{6-{[1,3-dihydroxy-2-(hydroxymethyl)prop-2-yl]amino}-4-{[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino}-s-triazin-2-yl}-piperazin-1-yl}-s-triazin2-yl}-7,11,18,21-tetraoxa-3,15-diazatrispiro[5.2.2.5.2.2]heneicosaneC105H140N40O32[α]D20 = +81.7 (c 0.5, DMSO)ee = 99% based on the starting materialSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol

3,15-Bis{4,6-bis{4-{6-{{[(2R,4S,5S)-5-(dimethylamino)-4-(4-nitrophenyl)-1,3-dioxan]-2-yl}methylamino}-4-{[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino}-s-triazin-2-yl}-piperazin-1-yl}-s-triazin2-yl}-7,11,18,21-tetraoxa-3,15-diazatrispiro [5.2.2.5.2.2]heneicosaneC141H172N48O36[α]D20 = +121.5 (c 0.5, DMSO)ee = 99% based on the starting materialsSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3- and diastereoselective of (1S,2S)-2-dimethylamino-1-(4-nitrophenyl)propane-1,3-diol

1,3,5-Tris{{15-{4,6-bis{4-{4-{[(2R,4S,5S)-5-(dimethylamino)-4-(4-nitrophenyl)-1,3-dioxan]-2-yl}methylamino-6-[(4S,5S)-4-(4-nitrophenyl)-1,3-dioxan-5-yl]amino-s-triazin-2-yl}-piperazin-1-yl}-s-triazin-2-yl}-7,11,18,21-tetraoxa-3,15-diazatrispiro [5.2.2.5.2.2]heneicosan-3-yl}-carbonyl}benzeneC243H297N75O63[α]D20 = +147.0 (c 0.5, DMSO)ee = 99% based on the starting materialsSource of chirality: diastereospecific ring closure of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3- and diastereoselective of (1S,2S)-2-dimethylamino-1-(4-nitrophenyl)propane-1,3-diol