Functional Evaluation of 3D Liver Models Labeled with Polysaccharide Functionalized Magnetic Nanoparticles.

Establishing a rapid evaluation system for drug screening is essential for the development of new drugs. To reproduce tissues/organs with functions closer to living organisms, three-dimensional (3D) culture evaluation using microfabrication technology has been reported in recent years. Culture on patterned substrates with controlled hydrophilic and hydrophobic regions (Cell-able) can create 3D liver models (miniature livers) with liver-specific Disse luminal structures and functions.

Identification and field bioassays of the sex pheromone of Eurytoma maslovskii (Hymenoptera: Eurytomidae).

Long-range sex pheromones are generally considered to be a main cue for mate recognition in the order Hymenoptera. Although considerable attention has been given to the identification of semiochemicals in the superfamily Chalcidoidea, which comprises 19 families, no study has identified active components in a field bioassay. We herein report the sensitive and selective pheromone communication system of the Korean apricot wasp, Eurytoma maslovskii (Eurytomidae), whose larvae feed on Prunus mume seeds.

New synthesis of a stereoisomeric mixture of methyl 12-trishomofarnesoate, a juvenile hormone mimic useful in sericulture by increasing silk production.

A mixture of (E,Z)-isomers of methyl 12-trishomofarnesoate (methyl 3,7,11-trimethyl-2,6,10-pentadecatrienoate), a juvenile hormone mimic, was synthesized in nine steps (32.6% overall yield) by starting from only four commercially available materials: 2-hexanone, vinylmagnesium bromide, methyl acetoacetate and trimethyl phosphonoacetate. The mimic is useful in increasing the yield of silk by elongating the larval period of the silkworm, Bombyx mori (L.

Sex pheromone of a coccoid insect with sexual and asexual lineages: fate of an ancestrally essential sexual signal in parthenogenetic females.

Sex pheromones play a central role in intersexual communication for reproduction in many organisms. Particularly in insects, reproductive isolation that leads to speciation is often achieved by shifts of pheromone chemistries. However, the divergence and evolution of pheromones remain largely unknown.

Asymmetric Formal Synthesis of Azadirachtin.

An asymmetric formal synthesis of azadirachtin, a potent insect antifeedant, was accomplished in 30 steps to Ley's synthetic intermediate (longest linear sequence). The synthesis features: 1) rapid access to the optically active right-hand segment starting from the known 5-hydroxymethyl-2-cyclopentenone scaffold; 2) construction of the B and E rings by a key intramolecular tandem radical cyclization; 3) formation of the hemiacetal moiety in the C ring through the α-oxidation of the six-membered lactone followed by methanolysis.

The neuropeptide tachykinin is essential for pheromone detection in a gustatory neural circuit.

Gustatory pheromones play an essential role in shaping the behavior of many organisms. However, little is known about the processing of taste pheromones in higher order brain centers. Here, we describe a male-specific gustatory circuit in Drosophila that underlies the detection of the anti-aphrodisiac pheromone (3R,11Z,19Z)-3-acetoxy-11,19-octacosadien-1-ol (CH503).

Stereochemical studies on pheromonal communications.

Pheromonal communications are heavily dependent on the stereochemistry of pheromones. Their enantioselective syntheses could establish the absolute configuration of the naturally occurring pheromones, and clarified the unique relationships between absolute configuration and bioactivity. For example, neither the (R)- nor (S)-enantiomer of sulcatol, the aggregation pheromone of an ambrosia beetle, is behaviorally active, while their mixture is bioactive.

Observation of Positively Charged Magnetic Nanoparticles Inside HepG2 Spheroids Using Electron Microscopy.

Magnetic resonance imaging (MRI) using magnetic nanoparticles has been used to diagnose vascular diseases as well as to monitor transplanted cells and tissues. In this study, we synthesized magnetic iron oxide nanoparticles (TMADM-03), electrically charged by the presence of a cationic end-group substitution of dextran, and observed these nanoparticles inside three-dimensional models of HepG2 spheroids, which mimic tissues. Patterned cell array glass disks were prepared to visualize the presence of TMADM-03 uptaken by HepG2 spheroids using transmission electron microscopy (TEM).

Synthesis and bioassay of the eight analogues of the CH503 male pheromone (3-acetoxy-11,19-octacosadien-1-ol) of the Drosophila melanogaster fruit fly.

Eight analogues of (3R,11Z,19Z)-CH503 (3-acetoxy-11,19-octacosadien-1-ol), the anti-aphrodisiac pheromone of male Drosophila melanogaster, were synthesized for a bioassay. These were the enantiomers of 3-acetoxy-11,19-octacosadiyn-1-ol (1), 3-acetoxyoctacosan-1-ol (2), (Z)-3-acetoxy-11-octacosen-1-ol (3), and (Z)-3-acetoxy-19-octacosen-1-ol (4). None of them were pheromonally active, indicating that the two double bonds at C-11 and C-19 were necessary for bioactivity.

Elucidating Structure-Bioactivity Relationships of Methyl-Branched Alkanes in the Contact Sex Pheromone of the Parasitic Wasp Lariophagus distinguendus.

The exoskeletons of insects are covered by complex mixtures of cuticular hydrocarbons (CHCs) which are involved in social and sexual communication. However, little is known about the relationship between the structures of CHCs and their behavioral activity. The key component of the contact sex pheromone of the parasitoid Lariophagus distinguendus is 3-methylheptacosane (3-MeC27), which is present in CHC profiles of both females and newly emerged males.

Synthesis of all the stereoisomers of 6-methyl-2-octadecanone, 14-methyl-2-octadecanone, and 6,14-dimethyl-2-octadecanone, sex pheromone components of the Lyclene dharma dharma moth, from the enantiomers of citronellal.

The enantiomers of citronellal were converted to all the stereoisomers of 6-methyl-2-octadecanone, 14-methyl-2-octadecanone, and 6,14-dimethyl-2-octadecanone, the female-produced sex pheromone components of the Lyclene dharma dharma moth. Three well-established procedures, the Wittig reaction, alkylation of alkynes, and acetoacetic ester synthesis, were employed for the carbon-carbon bond formation to connect the building blocks.

Synthesis of (1R,7Z)-1-methyl-7-hexadecenyl acetate, the female sex pheromone of the honey locust gall midge.

(1R,7Z)-1-Methyl-7-hexadecenyl acetate (1), the female sex pheromone of the honey locust gall midge (Dasineura gleditchiae), was synthesized from 6-hepten-1-ol in an 8.9% overall yield (eight steps). Hydrolytic kinetic resolution of (±)-1,2-epoxy-8-heptadecyne was the key step in the synthesis.

Metathesis-mediated synthesis of (R)-10-methyl-2-tridecanone, the southern corn rootworm pheromone.

(R)-10-Methyl-2-tridecanone, the female sex pheromone of the southern corn rootworm (Diabrotica undecimpunctata howardi Barber), was synthesized in 9 steps from methyl (S)-3-hydroxy-2-methylpropanoate in a 15.7% overall yield. Olefin cross metathesis between (R)-6-methyl-1-nonene and 5-hexen-2-one employing Grubbs' first-generation catalyst was the key step of the synthesis.

Bioactive natural products and chirality.

Mori's synthetic works on bioactive natural products in general and pheromones in particular started about 40 years ago to establish their absolute configurations and also to clarify their stereochemistry-bioactivity relationships. Results indicate that bioactive natural products are not always enantiomerically pure, and the stereochemistry-bioactivity relationships are not simple but complicated. For example, neither (R)- nor (S)-sulcatol, the aggregation pheromone of an ambrosia beetle, is behaviorally bioactive, whereas their mixture is active.

Protective group-free syntheses of (±)-frontalin, (±)-endo-brevicomin, (±)-exo-brevicomin, and (±)-3,4-dehydro-exo-brevicomin: racemic pheromones with a 6,8-dioxabicyclo[3.2.1]octane ring.

Protective group-free syntheses of four racemic pheromones with a 6,8-dioxabicyclo[3.2.1]octane ring were achieved in five or six steps from commercially available (±)-3-butyn-2-ol (6) and 2-alkenyl halides or 2-alken-1-ol by employing Lewis acid-catalyzed acetalization of δ, ε-epoxy ketones as the key reaction.

New syntheses of 1,7-dimethylnonyl propanoate, the western corn rootworm pheromone, in four different ways via cross metathesis, alkylation and coupling reactions.

A mixture of the four stereoisomers of 1,7-dimethylnonyl propanoate, the female sex pheromone of the western corn rootworm (Diabrotica virgifera virgifera LeConte), was synthesized in four different ways by employing one of the following four reactions as the key step: (i) cross metathesis using the Grubbs I catalyst, (ii) cross metathesis using the Grubbs II catalyst, (iii) alkylation of an alkynide anion, and (iv) Grignard coupling in the presence of dilithium tetrachlorocuprate. Although the cross metathesis approaches enabled two short syntheses (4 or 6 steps) of the pheromone to be achieved, the cheapest and most efficient synthesis was possible via Grignard coupling to give the desired pheromone in a 40% overall yield based on 2-methyl-1-butanol (8 steps).

New synthesis of (11Z,13Z)-11,13-hexadecadienal, the female sex pheromone of the navel orangeworm.

(11Z,13Z)-11,13-hexadecadienal, the female sex pheromone of the navel orangeworm (Amyelois transitella), was synthesized from commercially available 10-bromo-1-decanol in a 27% overall yield (8 steps). The synthesis was achieved by using 10-iododecanal, trimethylsilylacetylene and (Z)-1-bromo-1-butene as the key building blocks, employing Sonogashira-Hagihara coupling and Brown's hydroboration-protonolysis as the key reactions. The terminal formyl group was installed in the earlier stage of the synthesis rather than in the final step.

Significance of chirality in pheromone science.

Pheromones play important roles in chemical communication among organisms. Various chiral and non-racemic pheromones have been identified since the late 1960s. Their enantioselective syntheses could establish the absolute configuration of the naturally occurring pheromones and clarified the relationships between absolute configuration and bioactivity.