Synthesis and Characterization of a Highly Potent and Selective Isotopically Labeled Retinoic Acid Receptor Ligand, ALRT1550

Abstract

The syntheses of two labeled homologues of (2E,4E,6E)-7-(3,5-di-tert-butylphenyl)-3-methylocta-2,4,6-trienoic acid (ALRT1550, 2), [(13)CD(3)]ALRT1550 (3) and [(3)H]ALRT1550 (4), are described in this report. ALRT1550 is an exceptionally potent antiproliferative agent which is currently in phase I/II clinical trials for acute chemotherapy. Both homologues were prepared from commercially available 3,5-di-tert-butylbenzoic acid. Homologue [(13)CD(3)]ALRT1550 was labeled at the 7-position of the trienoic acid chain via addition of [(13)CD(3)]MgI to a Weinreb amide precursor. The preparation of [(3)H]ALRT1550 utilized novel methodology to synthesize a sterically hindered and site-specific tritium-labeled tert-butyl group. Saturation binding and Scatchard analysis of this ligand at the retinoic acid receptors are also described, along with competition binding (K(i)) values for a series of known retinoids using [(3)H]ALRT1550 or [(3)H]ATRA as the labeled probes.

Dioxygen Activation Using Schiff Base Macrocyclic Dinuclear Copper( I ) Complexes: Structurally Characterized Dioxygen Reaction Products

“…2-Methylisophthalaldehyde [50] , 5-tert-butylisophthalaldehyde [51] as well as 3a [33] and 3d [35] were prepared according to literature methods [32] . 1 H NMR and 13 C NMR spectra were recorded with a Bruker AMX400.…”

Specific Noncovalent Association of Chiral Large‐Ring Hexaimines: Ion Mobility Mass Spectrometry and PM7 Study

“…[50][51][52] Generalprocedure for synthesis of isotrianglimines 3a-e (Scheme S1, Supporting Information) All known compounds were identified by spectroscopic comparison with authentic samples.…”

Externally and Internally Functionalized Copper(II) β-Diketonate Molecular Squares

“…Compound 19 was prepared according to a procedure developed by Bennani et al to convert 5-tertbutyl-1,3-benzenedimethanol to 5-tert-butylisophthalaldehyde. 46 Pyridinium chlorochromate (PCC; 1.54 g, 7.15 mmol) and 3 g of Celite were added to a 250 mL flask equipped with an addition funnel under N 2 . Then, about 10 mL of dry CH 2 Cl 2 was added, and the mixture was vigorously stirred.…”