Synthetic Strategies TowardN‐Functionalized Cyclens

Abstract

Cyclen (1,4,7,10‐tetraazadodecane) is a widely used building block in the synthesis of many important molecules with applications spanning MRI contrast agents, fluorescent probes and heavy metals sensors. This review describes the various synthetic methodologies employed for the preparation of N‐functionalized cyclens such as: synthesis from acyclic precursors; alkylation or acylation of cyclen; and protecting group manipulations. Emphasis is given to synthetic strategies allowing for the selective, differential N‐functionalization of cyclen which is particularly useful for many modern applications.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Alternatives to Gadolinium-Based Metal Chelates for Magnetic Resonance Imaging

“…42,138,140,145,263–265 This method is quite general, and gives reasonable yields for both primary and secondary amines with a wide variety of functional groups. In addition, it can be extended to the synthesis of DOTA amides with mixed sidearms using selective protection-alkyation-deprotection-alkylation steps starting from cyclen 266–267. This route was also adapted for the synthesis of peptide-based DOTA tetraamides.…”

Improved Synthesis of 10-(2-Alkylamino-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic Acid Derivatives Bearing Acid-Sensitive Linkers

“…While commercially available 6 has been used in the synthesis of many bifunctional chelates, 27,28 the related methyl and ethyl esters 7 29–32 and 8 33–36 have found limited use. Few methods for the synthesis of 7 and 8 have been published.…”

Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes

“…The last mentioned modification employed reaction of 1,4,7,10-tetrakis(p-toluenesulfonyl)-1,4,7,10-tetraazadecane with 1,2-dibromoethane in DMF using potassium carbonate as a base. Probably the most efficient modification of the Richman-Atkins procedure is the reaction of 1,4,7-tris(p-toluenesulfonyl)-1,4,7-triazaheptane with O,N,O -tris(p-toluenesulfonyl)diethanolamine in presence of LiOH as a base [144][145][146], as shown in Scheme 3.32.…”

“…Here, we discuss only the most important strategies as the topic is very broad and has been recently reviewed [146,162]. The most common way of the cyclen N-functionalization is an alkylation with the appropriate electrophile.…”