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The use of agents that target both glia and neurons may represent a new strategy for the treatment of ageing disorders. Here, we confirmed the presence of the novel cyclic peptide Naturido that originates from a medicinal fungus (Isaria japonica) grown on domestic silkworm (Bombyx mori). We found that Naturido significantly enhanced astrocyte proliferation and activated the single copy gene encoding the neuropeptide VGF and the neuron-derived NGF gene. The addition of the peptide to the culture medium of primary hippocampal neurons increased dendrite length, dendrite number and axon length. Furthermore, the addition of the peptide to primary microglial cultures shifted CGA-activated microglia towards anti-inflammatory and neuroprotective phenotypes. These findings of in vitro glia–neuron interactions led us to evaluate the effects of oral administration of the peptide on brain function and hair ageing in senescence-accelerated mice (SAMP8). In vivo analyses revealed that spatial learning ability and hair quality were improved in Naturido-treated mice compared with untreated mice, to the same level observed in the normal ageing control (SAMR1). These data suggest that Naturido may be a promising glia–neuron modulator for the treatment of not only senescence, but also Alzheimer’s disease and other neurodegenerative diseases.

The stereocontrolled total synthesis of the C31 apocarotenoid paracentrone was achieved by sequential cross-coupling reactions using C5 boronic acid ester and iodo-substituted dienes, which were newly developed building blocks for elongation of the conjugated polyene systems at both their terminals.

Kaitocephalin (KCP) isolated from Eupenicillium shearii PF1191 is an unusual amino acid natural product in which serine, proline, and alanine moieties are liked with carbon-carbon bonds. KCP exhibits potent and selective binding affinity for one of the ionotropic glutamate receptor subtypes, NMDA receptors (Ki=7.8nM). In this study, new structure-activity relationship studies at C9 of KCP were implemented. Eleven new KCP analogs with different substituents at C9 were prepared and employed for binding affinity tests using native ionotropic glutamate receptors. Replacement of the 3,5-dichloro-4-hydroxybenzoyl group of KCP with a 3-phenylpropionyl group resulted in significant loss of binding affinity for NMDARs (Ki=1300nM), indicating an indispensable role of the aromatic ring of KCP in the potent and selective binding to NMDARs. Other analogs showed potent binding affinity in a range of 11-270nM. These findings would directly link to develop useful chemical tools toward imaging and labeling of NMDARs.

Tetragocarbones A and B were isolated from the propolis of an Australian stingless bee, Tetragonula carbonaria. These largely planar structures were proposed as a result of NMR analysis as well as comparison of their NMR data with those of related monomeric phloroglucinol derivatives. To elucidate relative and absolute stereochemistry of tetragocarbone A, the synthesis of the proposed structure of tetragocarbone A was performed. As a result, the synthetic compound bearing stereogenic centers 1R*,3R*,6S* was identical with naturally occurring tetragocarbone A. The absolute stereochemistry of tetragocarbone A was established to be 1R,3R,6S by chiral HPLC separation and X-ray analysis. Comparison of the NMR data of tetragocarbone A with that of tetragocarbone B indicated that tetragocarbone B would be a natural congener of tetragocarbone A.

To clarify the role of Juvenile hormone (JH) in the induction of oosorption in females of the stink bug Plautia stali Scott (Heteroptera: Pentatomidae), the effects of extirpation and implantation of the corpus cardiac-corpus allatum complex (CC-CA) are examined in fed and starved adults, respectively. Removal of CC-CA induces oosorption in fed females, whereas CC-CA implantation stimulates ovary development in starved females. Transection of the nervous connections between the brain and CC-CA also exerts a stimulatory effect on ovary development. Uptake of yolk protein by the oocytes, assessed in terms of incorporation of a fluorescence dye, occurs on the day after food deprivation but ceases within 1 day after allatectomy. When females are deprived of food, beginning on day 3 of adult life, and treated with JH III skipped bisepoxide (JHSB3) on the same day, their ovaries develop in a dose-dependent fashion. Approximately half of the starved females that received JHSB3 application on day 5 undergo oosorption in the terminal oocytes. This indicates that the critical starvation period for oosorption induction is approximately 2 days, and the earlier half of this period may reflect the time required for the brain to detect poor nutritional condition. During the latter half, in response to food deprivation, the brain inhibits JH biosynthesis by the corpus allatum through nervous connections, resulting in a low JH titre, which in turn induces oosorption.

This paper presents a spectroscopic investigation of deoxyperidinin, a synthetic peridinin analogue in which the carbonyl functional group in peridinin was replaced by a nonconjugated methylene group. Steady-state and ultrafast time-resolved absorption and fluorescence spectroscopic experiments are carried out on deoxyperidinin in n-hexane and acetonitrile at room temperature and in 2-methyltetrahydrofuran at 77 K. The spectra of deoxyperidinin have higher vibronic resolution compared to those of peridinin. The higher resolution is due to a substantial reduction in both molecular conformational disorder and inhomogeneous broadening of the spectra of deoxyperidinin compared to peridinin. Features in the steady-state absorption spectrum of deoxyperidinin that are not evident in the spectrum of peridinin are unambiguously assigned to the forbidden S0 (1(1)Ag(-)) → S1 (2(1)Ag(-)) absorption transition. The characteristics of both the steady-state and time-resolved spectra are interpreted using EOM-CCSD, SAC-CI, and MNDO-PSDCI quantum computational formalisms that provided a theoretical framework for understanding the photophysical properties of the molecules.

E -α-Stannyl-β-trimethylsilylethynylacrylates, which are effective building blocks for the polyconjugated ylidenebutenolides and its modified derivatives, were directly synthesized via novel E -selective ethynylstannylation of propiolic acid esters. These building blocks were applied to the syntheses of the ylidenebutenolide segment in the previous peridinin synthesis and a short chain Z -eneyne ester derivative, by the sequential Stille and Sonogashira couplings with the corresponding epoxide and vinyl iodide segments.

Juvenile hormone (JH) plays a pivotal role in many aspects of insect physiology. Although its presence was first reported in a blood-sucking bug belonging to the suborder Heteroptera (true bugs), JH species in the group has long been controversial. Although some recent studies proposed a putative JH molecular species in several Heteropteran species, it is not conclusive because physicochemical analyses were insufficient in most cases. Here, we studied this issue with an ultraperformance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) equipped with C18 and chiral columns in the bean bug Riptortus pedestris (Heteroptera, Alydidae), in which the JH species has long been controversial. Although a recent study describes JHSB3 as the major JH of this species, that finding was not conclusive because its chirality has not been clarified. In the present study, we detected methyl (2R,3S,10R)-2,3;10,11-bisepoxyfarnesoate, commonly named juvenile hormone III skipped bisepoxide (JHSB3), in the culture media of the corpora cardiaca-corpus allatum (CC-CA) complex and in the hemolymph of this species by a chiral ultraperformance liquid chromatography- tandem mass spectrometer (UPLC-MS/MS). Other JHSB3 stereoisomers were not detected. Topical application of JHSB3 effectively averted diapause. These results indicate that JHSB3 is the major JH of R. pedestris. The present study further revealed that JHSB3 and its (2R,3S,10S) isomer are more potent than (2S,3R,10R) and (2S,3R,10S) isomers, which suggests that there is a significance to the configuration of the 2,3-epoxide moiety in JH action. We further found a supplemental significance to the configuration of the 10-position.

An effective asymmetric α-phenylation of methyl ketones with triphenylaluminium in the presence of (+)-benzopyranoisoxazolidine has been developed. The reaction proceeds via the in situ formation of a chiral N-alkoxyenamine and the subsequent diastereoselective nucleophilic phenylation to provide α-phenylated products in moderate to good yields, with high enantioselectivities.

The stereocontrolled convergent synthesis of 19′-deoxyperidinin, 2, which might be a useful peridinin analog to understand the ICT characteristics, was efficiently achieved by sequential Pd-catalyzed cross-coupling reactions using bidirectionally extensible conjugated C5 olefin segments. The crucial 5(2H)-ylidenedihydrofuran function of 2 was successfully constructed by the Au-catalyzed regio- and stereoselective 5-exo-dig etherification.

Highly functionalized α-2,3-methanoamino acid esters were prepared by the cyclopropanation of dehydroaspartic acid esters with 2-methoxyfuran or 2-siloxyfuran derivatives. These reactions proceed smoothly in the absence of any catalysts, bases, additives, or solvents.

Terpene cyclization reactions are fascinating owing to the precise control of connectivity and stereochemistry during the catalytic process. Cyclooctat-9-en-7-ol synthase (CotB2) synthesizes an unusual 5-8-5 fused-ring structure with six chiral centers from the universal diterpene precursor, the achiral C20 geranylgeranyl diphosphate substrate. An unusual new mechanism for the exquisite CotB2-catalyzed cyclization that involves a carbon-carbon backbone rearrangement and three long-range hydride shifts is proposed, based on a powerful combination of in vivo studies using uniformly (13)C-labeled glucose and in vitro reactions of regiospecifically deuterium-substituted geranylgeranyl diphosphate substrates. This study shows that CotB2 elegantly demonstrates the synthetic virtuosity and stereochemical control that evolution has conferred on terpene synthases.

The direct addition reaction of chloroform to cyclopropenes under triethylborane-mediated radical reaction conditions to provide trichloromethylcyclopropanes has been developed. In contrast, using dimethylzinc as a radical initiator led to the formation of unconjugated esters via a domino sequence involving the addition of the trichloromethyl radical, rearrangement and ring-opening reactions.

Background Mass spectrometry-guided venom peptide profiling is a powerful tool to explore novel substances from venomous animals in a highly sensitive manner. In this study, this peptide profiling approach is successfully applied to explore the venom peptides of a Japanese solitary carpenter bee, Xylocopa appendiculata (Hymenoptera: Apoidea: Apidae: Anthophila: Xylocopinae: Xylocopini). Although interesting biological effects of the crude venom of carpenter bees have been reported, the structure and biological function of the venom peptides have not been elucidated yet. Methods The venom peptide profiling of the crude venom of X. appendiculata was performed by matrix-assisted laser desorption/ionization-time of flight mass spectroscopy. The venom was purified by a reverse-phase HPLC. The purified peptides were subjected to the Edman degradation, MS/MS analysis, and/or molecular cloning methods for peptide sequencing. Biological and functional characterization was performed by circular dichroism analysis, liposome leakage assay, and antimicrobial, histamine releasing and hemolytic activity tests. Results Three novel peptides with m/z 16508, 1939.3, and 1900.3 were isolated from the venom of X. appendiculata. The peptide with m/z 16508 was characterized as a secretory phospholipase A2 (PLA2) homolog in which the characteristic cysteine residues as well as the active site residues found in bee PLA2s are highly conserved. Two novel peptides with m/z 1939.3 and m/z 1900.3 were named as Xac-1 and Xac-2, respectively. These peptides are found to be amphiphilic and displayed antimicrobial and hemolytic activities. The potency was almost the same as that of mastoparan isolated from the wasp venom. Conclusion We found three novel biologically active peptides in the venom of X. appendiculata and analyzed their molecular functions, and compared their sequential homology to discuss their molecular diversity. Highly sensitive mass analysis plays an important role in this study. Electronic supplementary material The online version of this article (doi:10.1186/s40409-017-0119-6) contains supplementary material, which is available to authorized users.

The stereoselective synthesis of 7-oxanorbornane regarding as a key synthetic intermediate of tetrodotoxin (TTX) is reported. The bicyclo ring bearing various functional groups was successfully elaborated by a furan Diels–Alder (DA) reaction. The stereoselective installation of a quaternary amino carbon center to the DA product was achieved with the Tsuji–Trost allylation. The stereochemistry was unambiguously confirmed with X-ray.

A new method has been developed for the synthesis of 3-(1-aminoalkyl)-4-hydroxycyclobut-3-ene-1,2-dione [α-amino squaric acid (α-Asq)]-containing peptides using solid phase peptide synthesis according to an Fmoc protecting group strategy. FmocHN-Gly-[α-Asq]-Oi-Pr was successfully used as a coupling unit in this method, which allowed for the construction of α-Asq-containing hexapeptide libraries including Sq-Gly and Sq-Phe units using the Wang-resin. Peptides containing the α-Asq moiety exhibited inhibitory activity towards a digestive enzyme.

Recent studies have provided molecular evidence that gut symbiotic bacteria modulate host insect development, fitness and reproduction. However, the molecular mechanisms through which gut symbionts regulate these aspects of host physiology remain elusive. To address these questions, we prepared two different Riptortus-Burkholderia insect models, Burkholderia gut symbiont-colonized (Sym) Riptortus pedestris insects and gut symbiont-noncolonized (Apo) insects. Upon LC-MS analyses, juvenile hormone III skipped bisepoxide (JHSB3) was newly identified from Riptortus Apo- and Sym-female and male adults' insect hemolymph and JHSB3 titer in the Apo- and Sym-female insects were measured because JH is important for regulating reproduction in adult insects. The JHSB3 titer in the Sym-females were consistently higher compared to those of Apo-females. Since previous studies reported that Riptortus hexamerin-α and vitellogenin proteins were upregulated by the topical abdominal application of a JH-analog, chemically synthesized JHSB3 was administered to Apo-females. As expected, the hexamerin-α and vitellogenin proteins were dramatically increased in the hemolymph of JHSB3-treated Apo-females, resulting in increased egg production compared to that in Sym-females. Taken together, these results demonstrate that colonization of Burkholderia gut symbiont in the host insect stimulates biosynthesis of the heteroptera-specific JHSB3, leading to larger number of eggs produced and enhanced fitness in Riptortus host insects.

Facile and stereoselective syntheses of three different kinds of deuterium-labelled geranylgeraniol analogs have been achieved. LiAlD4 is used as the deuterium source to ensure high deuterium incor...

The first total synthesis of a monomeric phloroglucinol [(1R*,2S*)-2-hydroxy-2-isobutyl-4,4,6,6-tetramethyl-3,5-dioxocyclohexyl acetate] was achieved by stereoselective reduction of a symmetrical α...

The first total synthesis of (±)-triumphalone has been achieved in 8 steps from phloroglucinol. Synthetic triumphalone was converted to (±)-isotriumphalone in one step by the α-ketol rearrangement in a highly efficient manner. Although NMR data of the synthetic isotriumphalone were identical to the reported data, the X-ray crystallographic data did not support the proposed structure of isotriumphalone, but the cyclopentanone structure bearing the cis -diol moiety. We found that the rearrangement reaction smoothly took place in a protic solvent under thermal reaction conditions.

Dehydroamino acid (Dhaa) is recognized as a useful tool or substrate for amino acid and peptide research. Although the stereoselective synthesis of the thermodynamically more stable Z-Dhaa has been well examined and established, the stereoselective synthesis of E-Dhaa has still remained to be a challenging synthetic task. In this paper, a stereoselective synthesis of E-Dhaa esters using a new (α-diphenylphosphono)glycine is described. The characteristic aspects of the new method are summarized as follows: (i) metal additives play an important role in the promotion of E-stereoselectivities. (ii) the use of NaI was effected for the synthesis of E-Dhaas bearing an aryl substituent and an amino functionality, (iii) MgBr2·OEt2 and ZnCl2 contributed to improve the E-stereoselective synthesis of E-Dhaas bearing an alkyl substituent and an oxygen functionality, (iv) various protecting and functional groups were compatible under the reaction conditions, and (v) N-Cbz, Boc, and acyl-α-(diphenylphosphono)glycines were served for the stereoselective olefination reaction to provide the corresponding E-Dhaas.

The Prins cyclization of hydroxy or amino group-containing allenylsilanes with carbonyl compounds occurred at the allenic terminus in a regio- and stereoselective manner to give the di- or trisubstituted tetrahydrofurans, tetrahydropyrans, and pyrrolidines. During the reaction, the allenic axial chirality of the starting material was efficiently transferred to the newly formed carbon chiral centers of the product.

Asiasarum root (roots and rhizome of Asiasarum sieboldii or A. heterotropoides var. mandshuricum) has been frequently used in traditional Chinese medicinal formulas for the management of oral malodor syndrome caused by periodontal disease. However, there are no scientific reports concerning these effects and the mechanism of action. The objective of this study was to examine the inhibitory effects of Asiasarum root and its constituents on oral malodor syndrome and periodontal disease. A 50% ethanolic extract of Asiasarum root (AR-ext) showed L-methionine γ-lyase (METase) inhibitory activity at a concentration of 200 µg/mL, and inhibited interleukin (IL)-1β-stimulated matrix metalloproteinase (MMP)-1 secretion from human gingival fibroblasts (HGFs) at a concentration of 10 and 50 µg/mL without cytotoxic effects. Activity-guided fractionation of the AR-ext suggested that METase inhibitory activity was attributable to a mixture of linoleic and oleic acid, because these unsaturated fatty acids showed weak METase inhibitory activities. Similar fractionation using MMP-1 secretion inhibitory activity led to the isolation of two unsaturated fatty acid amides, (2E,4E,8Z,10E)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (1) and (2E,4E,8Z,10Z)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (2), as active constituents with inhibitory activity on MMP-1 secretion from HGFs. To elucidate the inhibition mechanism on MMP-1 secretion, the effect of 2 on mitogen-activated protein kinase (MAPK) phosphorylation was examined. Western blotting analysis revealed that 2 (10 µM) reduced the phosphorylation of p38 and c-Jun-N-terminal kinase. These results suggested that 2 suppresses intracellular MMP-1 expression and MMP-1 secretion from IL-1β-stimulated HGFs by down-regulation of MAPK phosphorylation.

The synthesis of anhydrorhodovibrin and two analogues has been achieved in a highly efficient manner using a new Horner–Wadsworth–Emmons reagent bearing the Weinreb amide.

Glutamate receptors mediate the majority of excitatory synaptic transmission in the central nervous system, and excessive stimulation of these receptors is involved in a variety of neurological disorders and neuronal damage from stroke. The development of new subtype-specific antagonists would be of considerable therapeutic interest. Natural products can provide important new lead compounds for drug discovery. The only natural product known to inhibit glutamate receptors competitively is (-)-kaitocephalin, which was isolated from the fungus Eupenicillium shearii and found to protect CNS neurons from excitotoxicity. Previous work has shown that it is a potent antagonist of some subtypes of glutamate receptors (AMPA and NMDA, but not kainate). The structure of kaitocephalin bound to the ligand binding domain of the AMPA receptor subtype, GluA2, is reported here. The structure suggests how kaitocephalin can be used as a scaffold to develop more selective and high affinity antagonists for glutamate receptors.

The highly diastereoselective synthesis of the marine natural product, (−)-manzacidin B, is described. A novel copper-catalyzed aldol reaction of the α-methylserine-derived aldehyde with an isocyanoacetate possessing (1 R )-camphorsultam as the chiral auxiliary proceeded in a highly diastereoselective manner to give the (4 R ,5 R ,6 R )-adduct, which was converted into manzacidin B in a few steps.

Total syntheses of juvenile hormones JH 0 and JH I have been achieved by a new iterative enol tosylate homologation strategy.

The structure–activity relationship of JHSB 3 isolated from the pentatomid bug, Plautia stali , was studied. Various synthetic analogs were synthesized and subjected to the juvenilizing activity tests using the last instar nymphs of P. stali . These studies indicated that the coexistence of the ester carbonyl group, two epoxides at C2,3 and C10,11 were proved to be crucial for the potent juvenilizing activity. Among the tested analogs, we found highly potent analogs in which the C6,7 double bond of JHSB 3 was saturated (0.1 μg/insect). The methoxy analogs in which the epoxide moiety at C10,11 was substituted with a methoxy group exerted a moderate juvenilizing activity.

Terpene cyclization is orchestrated by terpene cyclases, which are involved in the biosynthesis of various cyclic natural products, but understanding the origin and mechanism of the selectivity of terpene cyclization is challenging. In this work, we describe an in-depth mechanistic study on cyclooctatin biosynthesis by means of theoretical calculations combined with experimental methods. We show that the main framework of cyclooctatin is formed through domino-type carbocation transportation along the terpene chain, which we call a “cation-stitching cascade”, including multiple hydrogen-shifts and a ring rearrangement that elegantly determine the stereoselectivity.

A structure-activity relationship (SAR) study of kaitocephalin (KCP), known to be a potent naturally occurring NMDA receptor ligand, was performed. This study led us to the discovery of (7S)-kaitocephalin as a highly selective NMDA receptor ligand. It displayed a 22-fold higher degree of selectivity for the NMDA receptor over KCP, though the binding affinity of (7S)-KCP [Ki = 29 nM] was 3.7-fold less potent than that of KCP [Ki = 7.8 nM].

The Au(I)-catalyzed cyclization of an allenylglycine, which possessed a silyl group attached to the opposite side of the allenic terminus, occurred at the allenic center to produce the 2-amino-4-silylmethylene-substituted γ-butyrolactone 2a in a highly regio- and stereoselective manner. The presence of a silyl group at the allenic terminus is crucial for the present 5-endo-dig γ-butyrolactonization.

Juvenile hormone III skipped bisepoxide (JHSB(3)), methyl (2R,3S,10R)-2,3;10,11-bisepoxyfarnesoate was recently determined as a novel juvenile hormone (JH) in a stink bug, Plautia stali. To further confirm the biological function of JHSB(3) in this insect, its juvenilizing, reproduction-stimulating and diapause-terminating activities and the presence in the hemolymph were examined. Topical application of JHSB(3) to last instar nymphs inhibited their metamorphosis in a dose-dependent fashion. In allatectomized and diapausing adults, JHSB(3) application exerted stimulatory effects on the development of ovaries and ectadenia in females and males, respectively. JHSB(3) was detected from the hemolymph of reproductively active females by gas chromatography-mass spectrometry analysis while its titer in the hemolymph collected from diapausing adults was too low to be detected. These results demonstrated that JHSB(3) has biological function as a JH in P. stali. Topical application of JHSB(3), its stereoisomers and 10R-JH III also indicated that compounds with the 2R,3S-configuration were more potent than those with the 2S,3R-configuration and 2,3-double bond.

A novel silyl group-directed anti-SN2′ reaction of allylic alcohols under Mitsunobu reaction conditions is described. The Mitsunobu reaction of α-hydroxy-α-alkenylsilanes with a TBS or TIPS group gave the anti-SN2′ product, in which regio- and stereochemical outcomes of the reaction depended on the steric bulkiness of the silyl group.

K 2 HPO 4 is an efficient catalyst for thetransesterification reaction to produce methyl esters. Various functionalgroups are compatible under the mild reaction conditions.

Neuropeptides in neurosecretory cells of the pars intercerebralis (PI) and pars lateralis (PL) in the brain, and those in the corpus cardiacum-hypocerebral ganglion complex (CC-HG) and corpus allatum (CA) were examined by mass spectrometry and immunocytochemistry in adult females of the blowfly, Protophormia terraenovae. By using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and electrospray ionization quadrupole orthogonal acceleration time-of-flight mass spectrometry (ESI-Q-Tof MS) and MS/MS, 4 peptides (including myosuppressin and SIFamide) were detected in the PI, 12 peptides (including [Arg(7)]-corazonin and [Arg(7)]-corazonin(3)(-)(11)) in the PL, 13 peptides (including myosuppressin, [Arg(7)]-corazonin and [Arg(7)]-corazonin(3-11)) in the CC-HG, and 6 peptides in the CA. MALDI-TOF MS analysis of each tissue or organ was made in about 20 flies under diapause-inducing (LD 12:12 at 20 degrees C) and diapause-averting conditions (LD 18:6 at 25 degrees C). These molecular ion peaks did not distinctively differ between diapause-inducing and diapause-averting conditions. A peptide with an m/z value at 1395.1 was purified from 240 brains and the 2nd-10th amino acids were sequenced as -YRKPPFNGS-, corresponding to a partial sequence of SIFamide. Only two pairs of somata in the PI were immunoreactive to antisera against SIFamide, which were local neurons widely extending fibers throughout the brain neuropils.

The structure of the juvenile hormone (JH) in the suborder Heteroptera, order Hemiptera, has been known for a very long time to be different from the JH of other orders, but the structure has been a matter of controversy. The structure was first elucidated by an unprecedented approach involving the screening of a JH molecular library. The novel Heteroptera-specific JH (JHSB(3)) is a new category of JH that is featured by the skipped bisepoxide structure.

An efficient synthesis of (R)- and (S)-α-(hydroxymethyl)pyroglutamic acid esters from L -proline has been achieved. Each step was carried out on a decagram scale to access the N-protected (R)-ester in a highly efficient manner (44% overall yield from a proline-derived bicyclic substrate).

Novel sulfur-linked squaryl group-containing glutamate analogs were synthesized via addition and mono-substitution reactions of thiols to t -butyl methyl squarate (BMSQ: 7 ) in two steps. A glutamate analog prepared from Boc- l -Cys showed a potent binding affinity to KA/AMPA receptors.

The functionalized pyroglutamate core unit, (2R,4R)-3, which could be converted into the β-lactone/pyrrolidine or γ-lactone/pyrrolidine ring system of oxazolomycin A 1 and neooxazolomycin 2, and which possesses an exomethylene group at C3 as a scaffold for the construction of their C3 polyene segment, was synthesized by the Michael reaction of a glycine Schiff base 4 with the α,β-disubstituted acrylate 8 as the key step.

A short and stereoselective synthesis of manzacidins A and C, and their enantiomers was achieved via stereoselective hydrogenation reactions of dehydroamino acid esters 5 – 8 using a chiral Rh catalyst.

Two novel biologically active peptides, Eumenine mastoparan-OD and Orancis-Protonectin, were isolated from a solitary wasp, Orancistrocerus drewseni drewseni (Eumeninae, Vespidae). MALDI-TOF MS analysis of a small amount of the crude venom gave two intensive molecular-related ion peaks at m/z 1269.9 and 1552.9 that were expected to be novel based on a peptide database search. Purification of the crude venom by HPLC gave two peptide fractions, P-1 and P-2. The amino acid sequence of P-1 (GRILSFIKAGLAEHL-NH2) and P-2 (ILGIITSLLKSL-NH2) were determined by ESI-MS/MS, automated Edman degradation, and amino acid analysis. According to the high sequence homology with those of mastoparan and protonectin, P-1 and P-2 were labeled Eumenine mastoparan-OD and Orancis-Protonectin, respectively. Orancis-Protonectin is the first example of a protonectin analog isolated from the venom of a solitary wasp. The hemolytic activities of these new peptides were more potent than that of mastoparan.

A biologically active quinone that exhibits a growth-inhibitory effect on rat liver cancer cells was isolated from the nest of a social wasp, Vespa simillima (Vespinae, Vespidae). The structure was unambiguously determined by NMR and synthetic experiments and identified as being 7,8-seco-para-ferruginone. The synthetic quinone showed potent growth-inhibitory effects on rat hepatoma cells (IC50 value=1.9 microM). Morphological analyses of dRLh84 cells using the synthetic compound were tested. Chromatin coagulation was induced by the synthetic compound at 31.6 muM.

The Au(I)-catalyzed novel conversion of α-acyloxy-α-alkynylsilanes to α-acyloxy-α′-silyl ketones is reported. Ph3PAuOTf in dioxane in the presence of 1 equiv of H2O efficiently catalyzed both the [3,3] sigmatropic rearrangement and allenic transformation of the resulting ester to give the α-acyloxy-α′-silyl ketones in a one-pot procedure.

Novel Leu-enkephalin analogs 10a – c in which the Tyr 1 , Gly 2 , or Gly 3 residue of Leu-enkephalin 9 was replaced with α-amino squaric acid analog Sq-Tyr 8b or Sq-Gly 8a were synthesized starting from 14 or 18 . Conformational analysis of 10a – c together with its model compound 26 and their opioid receptor binding activity were evaluated.

Highly functionalized α-2,3-methanoamino acid esters were prepared by the cyclopropanation of dehydroaspartic acid esters with 2-methoxyfuran or 2-siloxyfuran derivatives. These reactions proceed smoothly in the absence of any catalysts, bases, additives, or solvents.