WIN 64821, a new competitive antagonist to substance P, isolated from an Aspergillus species: structure determination and solution conformation

Abstract

Two new diketopiperazine dimers, WIN 64821 (la) and WIN 64745 (2), were isolated from an Aspergillus culture originally isolated from soil and their structures established on the basis of chemical and spectroscopic evidence. The dimer la has Cl symmetry with each of two equivalent

Nickel-catalyzed dimerization of pyrrolidinoindoline scaffolds: systematic access to chimonanthines, folicanthines and (+)-WIN 64821

“…cultures (Scheme 5). 23 Removal of Boc groups with TMSI and site-selective condensation of the resulting tetraamine with 20 followed by diketopiperazine formation upon heating afforded (+)-WIN 64821 (6). 9a,21f, 24 De Lera and co- …”

Cyclo-(TRP-PHE) diketopiperazines from the endophytic fungus Aspergillus versicolor isolated from Piper aduncum

“…The structures of the compounds were elucidated using 1-D, 2-D NMR (Table 1 and 2), MS techniques were also carried out and comparison was made with the literature data. [7][8][9][10][11][12] The compounds were identified as three peptide derivatives: cyclo-(tryptophyl-phenylalanyl) (2), diketopiperazine dimer WIN 64821 (3), 3-hydroxy-15H-tryptophenaline (4) and 2-hydroxy-6-N-isopentenyl-adenine (5), 4-methoxyphtalide (1) and 3-hydroxy-4-(1-hydroxy-1,5-dimethyl-hexyl) benzoic acid (6) (Figure 1). The molecular formula C 9 H 8 O 3 of compound 1 was established by 13 C NMR and HREIMS analysis, which showed the protonated molecular ion peak [M+H] + at m/z 165.0597 (Calcd.…”

“…Accordingly, this result implies that compound 3 has the same absolute configuration as the compound isolated from Aspergillus sp. 9 The molecular formula C 20 H 19 N 3 O 3 of compound 4 was established by 13 (dd, J = 13.0; 11.5 Hz, H-10b)] are, in essence, neighbors of the carbon attached to oxygen, confirming the hydroxyl group bonded to C-3. The absolute configuration of C-11 was based on that of the cyclic (L,L)-dipeptide (2).…”

Polymorphism and phase transition behavior of 6,6′-bis(chloromethyl)-1,1′,4,4′-tetramethyl-3,3′-(p-phenylenedimethylene)bis(piperazine-2,5-dione)

“…Natural products, such as ditryptophenaline (Springer et al, 1977), WIN-64821,WIN-64745 (Barrow et al, 1993;Popp et al, 1994) and leptosin S (Yamada et al, 2004) incorporate a 3a,3a 0 -bispyrrolidinoindoline core with contiguous stereogenic quaternary carbons and display cytotoxicity in various cell lines. Perhaps the most interesting is a C 2 -symmetrical piperazine-2,5-dione (WIN-64821), which is a competitive substance-P antagonist against the human NK1 receptor at submicromolar concentrations (Barrow et al, 1993;Popp et al, 1994;Oleynek et al, 1994;Sedlock et al, 1994) and also serves as an antagonist of the cholecystokinin type-B receptor (Hiramoto et al, 1994). The title compound, (I), was synthesized as part of a wider project to develop new synthetic methods for the preparation of bridged bis-DKPs (Polaske et al, 2009).…”