Cyclo(delta-Ala-L-Val)

The title compound, C(12)H(19)BrN(4)O, represents the minor component of the two products obtained in a series of transformations involving the Grignard reaction of tert-butoxy-carbonyl-protected 4-amino-cyclo-hexa-none with MeMgBr, and subsequent inter-action of the obtained amino-substituted cyclo-hexa-nol with 4-chloro-6-methyl-pyrimidin-2-amine followed by bromination with N-bromo-succinimide. The X-ray structure showed that this product represents a trans isomer with respect to the amino and hydr-oxy substituents in the cyclo-hexyl ring; the dihedral angle between the amino-pyrimidine plane and the (noncrystallographic) mirror plane of the substituted cyclo-hexyl fragment is 33.6 (3)°. Only two of the four potentially 'active' H atoms participate in inter-molecular N-H⋯O and O-H⋯N hydrogen bonds, linking the mol-ecules into layers parallel to the (10) plane.

Peroxisome proliferator-activated receptor (PPAR) expression has been implicated in pathological states such as cancer, inflammation, diabetes, and neurodegeneration. We isolated natural PPAR agonists-eight 2,5-diketopiperazines-from the jellyfish-derived fungusAspergillus flavus. Cyclo-(L-Pro-L-Phe) was the most potent PPAR-γ activator among the eight 2,5-DKPs identified. Cyclo-(L-Pro-L-Phe) activated PPAR-γ in Ac2F rat liver cells and SH-SY5Y human neuroblastoma cells. The neuroprotective effect of this partial PPAR-γ agonist was examined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase release, and the Hoechst 33342 staining assay in SH-SY5Y cells. Our findings revealed that cyclo-(L-Pro-L-Phe) reduced hydrogen peroxide-induced apoptosis as well as the generation of reactive oxygen species. Rhodamine 123 staining and western blotting revealed that cyclo-(L-Pro-L-Phe) prevented the loss of mitochondrial membrane potential and inhibited the activation of mitochondria-related apoptotic proteins, such as caspase 3 and poly (ADP-ribose) polymerase. Moreover, cyclo-(L-Pro-L-Phe) inhibited the activation and translocation of nuclear factor-kappa B. Thus, the partial PPAR-γ agonist cyclo-(L-Pro-L-Phe) demonstrated potential neuroprotective activity against oxidative stress-induced neurodegeneration in SH-SY5Y cells.

THE TITLE COMPOUND [SYSTEMATIC NAME: 14,15-dihy-droxy-7,7-dimethyl-13-(propan-2-yl)tricyclo-[9.4.0.0(3,8)]penta-deca-1(11),3(8),9,12,14-pentaen-4-one], C(20)H(24)O(3), is a new icetexane diterpenoid which was isolated from the roots of Premna obtusifolia (Verbenaceae). The mol-ecule has three fused rings: a cyclo-hexenone, a central cyclo-heptene and a benzene ring. The cyclo-hexenone ring is in an envelope conformation, whereas the cyclo-heptene ring is in a twisted boat conformation. Intra-molecular O-H⋯O hydrogen bonds generate S(5) and S(8) ring motifs. In the crystal, mol-ecules are linked into dimers through O-H⋯O hydrogen bonds. These dimers are arranged in to sheets parallel to the ac plane. C-H⋯O and weak C-H⋯π inter-actions are also present.