Solid-Phase Synthesis of 5-Noranagrelide Derivatives

Abstract

Solid-phase synthesis of 1H-benzo[d]imidazo[1,2-a]imidazol-2(3H)-one derivatives employing Fmoc-α-amino acids and nitroaryl fluorides as key building blocks has been developed. The Fmoc-α-amino acids immobilized on Wang resin, equipped with a piperazine carbamate linker, were transformed to o-nitroanilines in two steps. After reduction of the nitro group, the corresponding o-phenylenediamines gave the 2-aminobenzimidazole scaffold by reaction either with cyanogen bromide or with Fmoc-NCS. Cleavage from the polymer support and further cyclization afforded the target compounds. The developed methodology represents a versatile and simple approach for the preparation of various corresponding 1H-benzo[d]imidazo[1,2-a]imidazol-2(3H)-ones from a large number of commercially available building blocks.

Solid-Phase Synthesis of 2,3-Dihydrobenzo[f][1,2,5]thiadiazepin-4(5H)-one 1,1-Dioxides with Three Diversity Positions

“…In our recent article, it was demonstrated that the configuration remains untouched if the amino acid is immobilized with use of HOBt/DIC strategy . In contrast, full or partial racemization of the α-amino acid stereocenter can occur during the acylation that yields the heterocyclic moiety. To evaluate the stereochemical outcome of the synthetic method, compound 6 DL ( 1 , 1 , 1 ) was prepared as the racemic standard.…”

Biomimetic and bioinspired molecular electrets. How to make them and why does the established peptide chemistry not always work?

“…Ion pairing between N + (C 4 H 9 ) 4 and S 2 O 4 2− makes the reducing agent soluble in organic media allowing it to diffuse to the nitro compounds. While it has been successfully used for solid-phase synthetic protocols [170,171], our tests reveal that this PTC approach does not produce 15 from 14 in acceptable yields.…”

Solid-Phase Synthetic Strategies for the Preparation of Purine Derivatives

“…After compound 19 was immobilized on the resin, the reduction of the nitro group was performed using sodium dithionate. It should be noted that the solid-phase reduction with Na 2 S 2 O 4 is typically performed in a biphasic system of DCM/H 2 O with a phase transfer catalyst; − in this particular case, the use of Argogel resin enabled the use of aqueous dioxane. Finally, the purine scaffold was cyclized via the corresponding thioureas 23 to obtain the 8-alkyl/arylamino substituted purines 25 .…”