Fluorescent ligands for the histamine H2 receptor: synthesis and preliminary characterization

Synthesis of 3′‐BODIPY‐Labeled Active Esters of Nucleotides and a Chemical Primer Extension Assay on Beads

“…In the case of BODIPY dye 13, all attempts to hydrolyze the ester moiety by using alkaline hydroxides, carbonates, [25] or pig liver esterase (PLE) [21] again led to impure product in low yield. Synthetic procedures that involved a free acid as the starting material and that avoided the hydrolytic step [26] were considered, but reported yields are so low that they were not pursued.…”

“…[21] Briefly, to a stirred solution of 9 (1.066 g, 6.96 mmol) and 3,5-dimethyyl-1H-pyrrole-2-carbaldehyde (0.943 g, 7.66 mmol, 1.1 equiv.) in CH 2 Cl 2 (55 mL) was added dropwise POCl 3 (1.175 g, 7.66 mmol, 1.1 equiv.)…”

“…First, we synthesized 14 by following literature protocols [20,21] (see Supporting Information). This route produced large amounts of side products during an early condensation step and required a costly trichloroethyl ester.…”

“…For the route leading to 13, aldehyde 10 was pre-pared in three steps by pyrrole synthesis, [23] with N-allyl-4-methoxybenzamide, [24] followed by Vilsmayer Haack formylation in an overall yield of 70 %. BODIPY dyes 11 and 12 were then prepared in moderate to good yield (41 and 71 %, respectively) by using the method of Malan et al [21] Liberation of the carboxylic acids from esters proved challenging at first. Even after careful optimization studies involving a series of bases (LiOH, KOH, Li 2 CO 3 , Na 2 CO 3 , K 2 CO 3 , Cs 2 CO 3 ), solvents, and reaction temperatures, basic conditions gave no more than 63 % yield of 14.…”

Highly Potent Fluorescence‐Tagged Nonimidazole Histamine H3 Receptor Ligands

“…Few fluorescent ligands have been described for the histamine receptors. [19][20][21] A commercially available fluorescent histamine derivate (Bodipy FL histamine; Molecular Probes) is able to show lysosomal localisation, [22] but to our knowledge receptor binding properties have not been described.…”