Dendrimers and methods for their preparation
View Patent ↗Provided are new dendrimers and processes for making them. The dendrimers are derived from a nitroalkyloxirane compound of formula (III): wherein R 1 , R 2 , and R 3 are as described herein.
1. A dendrimer comprising:
a core comprising 2 or more terminal residues and derived from a polyvalent organic molecule;
from 1 to 8 generations emanating radially from the core, the 1 to 8 generations comprising:
from 0 to 7 interior generations comprising 2 or more molecular units independently having formula A:
wherein R 1 and R 2 are independently H or C 1 -C 10 alkyl, or R 1 and R 2 , together with the carbon to which they are attached, form a C 3 -C 12 cycloalkyl ring optionally substituted with C 1 -C 6 alkyl, and R 3 is H, C 1 -C 10 alkyl, or phenyl, and wherein the innermost interior generation is attached to the core through the terminal residues;
an exterior layer attached to the outermost of the interior generations or to the core through the terminal residues if no interior generations are present, the exterior layer comprising 2 or more molecular units independently having formula B:
wherein R 4 and R 5 are each H, or R 4 , R 5 and the nitrogen to which they are attached form a NO 2 group,
wherein the terminal residues are amine residues.
2. The dendrimer of claim 1 wherein R 1 and R 2 are each C 1 -C 10 alkyl.
3. The dendrimer of claim 1 wherein R 3 is H.
4. The dendrimer of claim 1 wherein when the core is an aliphatic acyclic residue containing 2 amine residues, the dendrimer comprises at least 2 generations.
5. The dendrimer of claim 1 of the structure:
6. A process for making a dendrimer comprising:
a core comprising 2 or more terminal residues and derived from a polyvalent organic molecule;
from 1 to 8 generations emanating radially from the core, the 1 to 8 generations comprising:
from 0 to 7 interior generations comprising 2 or more molecular units independently having formula A:
wherein R 1 and R 2 are independently H or C 1 -C 10 alkyl, or R 1 and R 2 , together with the carbon to which they are attached, form a C 3 -C 12 cycloalkyl ring optionally substituted with C 1 -C 6 alkyl, and R 3 is H, C 1 -C 10 alkyl, or phenyl, and wherein the innermost interior generation is attached to the core through the terminal residues;
an exterior layer attached to the outermost of the interior generations or to the core through the terminal residues if no interior generations are present, the exterior layer comprising 2 or more molecular units independently having formula B:
wherein R 4 and R 5 are each H, or R 4 , R 5 and the nitrogen to which they are attached form a NO 2 group,
wherein the terminal residues are amine residues, the process comprising:
(a) providing a polyvalent organic molecule comprising 2 or more terminal functional groups;
(b) combining a nitroalkyloxirane compound of formula III:
with the polyvalent organic molecule in sufficient amount such that the nitroalkyloxirane compound reacts with the terminal functional groups of the polyvalent organic molecule to form a nitro compound comprising a core and 2 or more molecular units connected to the core and independently having formula B-1:
(c) optionally reducing the nitro compound to form an amine compound comprising the core and 2 or more molecular units connected to the core and independently having formula B-2:
(d) optionally repeating steps (b) and/or (c) from 1 to 7 times, wherein the amine compound instead of the polyvalent organic molecule is reacted with a nitroalkyloxirane compound of formula III,
wherein the terminal functional groups of the polyvalent organic molecule are amines.
7. The process of claim 6 wherein R 4 , R 5 and the nitrogen to which they are attached form a NO 2 group, and the dendrimer is further functionalized to form a functionalized dendrimer by: base catalyzed reaction with an aldehyde (Henry Reaction); base catalyzed reaction with an α,β-unsaturated ester or nitrile (Michael Reaction); base catalyzed reaction with an aldehyde in the presence of an amine (Mannich Reaction); strong base catalyzed reaction with an alkyl halide (alkylation); strong base catalyzed reaction with an acyl chloride or activated ester (acylation); or base catalyzed halogenation.
8. The process of claim 6 wherein R 4 and R 5 are H, and the dendrimer is further functionalized to form a functionalized dendrimer by reaction with an epoxide, acrylate, or acid chloride.
9. The process of claim 7 wherein the dendrimer is further functionalized with a dye, a drug, or a drug targeting molecule.
10. The process of claim 8 wherein the functionalized dendrimer is of the structure: