Synthesis of Rigid Multivalent Scaffolds Based on Adamantane

Abstract

An efficient route to novel 1,3,5,7-tetrasubstituted derivatives of adamantane is described. This route starts from adamantane and gives the tetrafunctionalized derivative 9 in eight steps with an overall yield of 23%. These tetrahedrally shaped molecules possess three identical arms terminated by an activated carboxylic acid derivative and a protected amino function in the 1-position. We propose these tetravalent cage compounds such as 9 as scaffolds for the assembly of ligand/marker conjugates for studies of multivalent ligand receptor interactions. [reaction: see text]

Synthesis of tripodal catecholates and their immobilization on zinc oxide nanoparticles

“…A common synthetic precursor for the synthesis of suitable tripodal catecholates is the AB 3 -scaffold 1 [40–42] (Scheme 1) which is readily available in a few steps from adamantane as a cheap starting material [43]. Amine 1 was coupled to a commercially available PEG-carboxylate (5 kDa) with EDC/DMAP.…”

Production of Multimeric Prostate-Specific Membrane Antigen Small-Molecule Radiotracers Using a Solid-Phase 99mTc Preloading Strategy

“…The work of Whitesides and colleagues (13) suggests that by decreasing the off-rate, multivalency can permit a small molecule to ''out-compete'' endogenous competitors. To test this hypothesis, while maintaining overall small size, we have developed a tri-NHS ester derivative of adamantane (14), which permits conjugation of up to 3 targeting ligands (such as GPI) in addition to a contrast agent or radiotracer. Recently, we have added a 6-carbon linker to improve radiotracer conjugation and have purified a series of GPI derivatives with increasing valency (Fig.…”

“…A general approach to solving these problems was proposed by Whitesides' group (13) and involves multimerizing binding epitopes into an optimally spaced rigid structure. To accomplish this, we have created a tri-NHS adamantane derivative (14), which permits the conjugation of up to 3 (same or different) targeting ligands. The molecule also has an isolating linker and a deprotectable primary amine for subsequent conjugation to contrast agents, radiotracers, or therapeutics.…”

Rigid C3‐Symmetric Scaffolds Based on Adamantane

“…The rigid alkyne linkage in tricarboxylic acid 20, for example, can be converted quantitatively by hydrogenation into a more flexible alkyl spacer in 23 [17] (Scheme 3). A shorter and more practical approach to semi-rigid scaffolds like 23 again starts from tribromoadamantane.…”

“…Adamantane-based scaffolds 3 share the tripodal arrangement of R groups with cyclohexane cores like 2, but are more rigid and most importantly permit introduction of additional functionality into the fourth bridgehead position without disturbing the geometry of the molecule or interfere with binding processes at the R groups. [17] Although some adamantane-based C 3 -symmetric scaffolds 3 are known, they have rarely been used as scaffolds for the assembly of functional molecules with threefold geometry. [18] This is probably due to a lack of proper functional groups in known scaffolds 3 or their difficult chemical synthesis.…”