Triazine dendrimers with orthogonally protected amines on the periphery. Masking amines with Dde and BOC groups provides an alternative to carrying protected alcohols and disulfides through an iterative synthesis.
An orthogonally protected dendrimer based on melamine displaying 24 Boc-protected amines (Boc is t-butoxycarbonyl) and 12 Dde-protected (Dde is N-2-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl) amines was synthesized using a convergent route in four linear steps in 43% overall yield to provide 5 g of product. Postsynthetic manipulation of this dendrimer produced a 57 kDa macromolecule bearing poly(ethylene glycol) groups and pyridyldisulfide groups linked via carbamate and amide bonds, respectively. These orthogonally protected amines provide more reactive handles for chemical modification when compared to other groups, notably hydroxyls, that have been explored. In addition, the Dde group proves to be more stable to the synthetic methods employed than do the disulfides used previously. Monochlorotriazine and dichlorotriazine intermediates are invaluable as a route for eliminating unwanted byproducts arising from over-substitution of the triazine ring. Routes requiring three reactions on a simple, generation zero core versus six reactions on a generation one core are compared.
Department of Chemistry, Texas A&M University, College Station, Texas 77843-3255, USA.
Alona P
AP
Umali
Hannah L
HL
Crampton
Eric E
EE
Simanek
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008958:Models, Molecular; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D012015:Reference Standards; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014227:Triazines / Q000737:chemistry*
D000588:Amines; D050091:Dendrimers; D004220:Disulfides; D014227:Triazines; D011092:Polyethylene Glycols