Search

We report here a homo‐Mannich reaction of cyclopropanol with an iminium ion, generated by an asymmetric allylic dearomatization of indole, to construct a tricyclic hydrocarbazole core, which is shared by a variety of monoterpenoid indole alkaloids across families. Through this approach, an all‐carbon quaternary stereogenic center as well as an allyl and a ketone group were installed. Using this functionalized hydrocarbazole as the structural platform, D ring and E rings of different sizes (i.e. five‐, six‐, and seven‐membered) were successively or simultaneously assembled, leading to a collective asymmetric synthesis of seven alkaloids belonging to the ibophyllidine, Aspidosperma, Kopsia, and Melodinus alkaloid families. [ABSTRACT FROM AUTHOR]

We report here a homo‐Mannich reaction of cyclopropanol with an iminium ion, generated by an asymmetric allylic dearomatization of indole, to construct a tricyclic hydrocarbazole core, which is shared by a variety of monoterpenoid indole alkaloids across families. Through this approach, an all‐carbon quaternary stereogenic center as well as an allyl and a ketone group were installed. Using this functionalized hydrocarbazole as the structural platform, D ring and E rings of different sizes (i.e. five‐, six‐, and seven‐membered) were successively or simultaneously assembled, leading to a collective asymmetric synthesis of seven alkaloids belonging to the ibophyllidine, Aspidosperma, Kopsia, and Melodinus alkaloid families. [ABSTRACT FROM AUTHOR]

This study aimed to examine the antiviral effects of shikonin ester ((R)-1-(5, 8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl3-(1H- indol-3-yl) propanoate (PMM-034) against influenza A (H1N1) virus. We investigated PMM-034 anti-H1N1 activity and its effect on caspase 3 gene expression during cellular apoptosis after influenza virus infection in vitro. Neuraminidase (NA) inhibition was assessed in comparison with oseltamivir in the influenza virus standard strains A/PR/8/34 to understand the viral mechanism. MDCK and A549 cells were used to investigate influenza viral infection and the structure-activity relationship between PMM-034 and NA was evaluated by pharmacophore-based docking modeling. The production of viral protein was tested by western blot. A/PR/8/34 induced cell inhibition but this was reduced by PMM-034 to 16 μg/mL and this showed a selective index of 10 mM. PMM-034 inhibited NA in a dose dependent manner, similar to oseltamivir inhibition. A sharp decrease in viral nucleocapsid protein mRNA was observed in infected cells after treatment with PMM-034. Apoptosis of infected A459 cells was inhibited by PMM-034 with decreased caspase 3 levels. ARG 118, ARG 152, ARG 371 and GLU 227 in the binding pocket of NA bound to PMM-034 in the docking model. Taken together, these results suggest PMM-034 shikonin ester blocked H1N1 infection and might be a potential anti-H1N1 drug. [ABSTRACT FROM AUTHOR]

We report here a concise, collective, and asymmetric total synthesis of sarpagine alkaloids and biogenetically related koumine alkaloids, which structurally feature a rigid cage scaffold, with L‐tryptophan as the starting material. Two key bridged skeleton‐forming reactions, namely tandem sequential oxidative cyclopropanol ring‐opening cyclization and ketone α‐allenylation, ensure concurrent assembly of the caged sarpagine scaffold and installation of requisite derivative handles. With a common caged intermediate as the branch point, by taking advantage of ketone and allene groups therein, total synthesis of five sarpagine alkaloids (affinisine, normacusine B, trinervine, Na‐methyl‐16‐epipericyclivine, and vellosimine) with various substituents and three koumine alkaloids (koumine, koumimine, and N‐demethylkoumine) with more complex cage scaffolds has been accomplished. [ABSTRACT FROM AUTHOR]

We report here a concise, collective, and asymmetric total synthesis of sarpagine alkaloids and biogenetically related koumine alkaloids, which structurally feature a rigid cage scaffold, with L‐tryptophan as the starting material. Two key bridged skeleton‐forming reactions, namely tandem sequential oxidative cyclopropanol ring‐opening cyclization and ketone α‐allenylation, ensure concurrent assembly of the caged sarpagine scaffold and installation of requisite derivative handles. With a common caged intermediate as the branch point, by taking advantage of ketone and allene groups therein, total synthesis of five sarpagine alkaloids (affinisine, normacusine B, trinervine, Na‐methyl‐16‐epipericyclivine, and vellosimine) with various substituents and three koumine alkaloids (koumine, koumimine, and N‐demethylkoumine) with more complex cage scaffolds has been accomplished. [ABSTRACT FROM AUTHOR]

Herein, a two-photon mitochondria-targeting fluorescent probe (TPNP) which can be activated by the azo reductase (AzoR) has been developed for imaging the hypoxic microenvironment of tumors in vivo. The probe TPNP showed a low detection limit (LOD = 1.85 eq), high selectivity, and considerable steadiness in different pH conditions (3.0–11.0). In living cells, it could co-locate with the commercial dye in the mitochondria (co-localization coefficient: 0.92) and indicate hypoxia in both one-photon and two-photon fluorescence imaging. Its AzoR-activation mechanism was further verified by the docking simulation as well as the experiments of adding AzoR or electron transporter inhibitors. Moreover, the in vivo real-time fluorescence imaging proved that TPNP could monitor hypoxia and the tumor progression in mouse tumor models. Overall, this designed probe exhibited high sensitivity, synthetic ease, and excellent fluorescent properties, which might therefore enlighten new ideas for the diagnosis of tumors in future studies. • A new hypoxia-sensitive fluorescent probe (TPNP) for tumor detection is reported. • TPNP exhibited high sensitivity, synthetic ease, and impressive fluorescent properties. • TPNP can monitor the presence of solid tumors in the xenograft mice model. [ABSTRACT FROM AUTHOR]