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To obtain potent liver X receptor (LXR) agonists, a structure-activity relationship study was performed on a series of tert-butyl benzoate analogs. As the crystal structure analysis suggested applicable interactions between the LXR ligand-binding domain and the ligands, two key functional groups were introduced. The introduction of the hydroxyl group on the C6-position of the benzoate part enhanced the agonistic activity in a cell-based assay, and the carboxyl group in terminal improved the pharmacokinetic profile in mice, respectively. The obtained compound 32b increased blood ABCA1 mRNA expression without plasma TG elevation in both mice and cynomolgus monkeys.

Herein we report the asymmetric synthesis of (3S)-(tert-butyldimethylsilyloxy)methylcyclopentan-1-one (S)-3 as a practical chiral synthon for a wide range of pharmaceutical and/or natural products, using Lipshutz’s asymmetric copper-catalyzed conjugate reduction. This method makes it feasible to prepare a conformationally constrained cyclopentane analogue 12, which is one of the key intermediates for the synthesis of novel sphingosine 1-phosphate-1 receptor agonists.

A novel orally bioavailable renin inhibitor, DS-8108b (5), showing potent renin inhibitory activity and excellent in vivo efficacy is described. We report herein the synthesis and pharmacological effects of 5 including renin inhibitory activity in vitro, suppressive effects of ex vivo plasma renin activity (PRA) in cynomolgus monkey, pharmacokinetic data, and blood pressure-lowering effects in an animal model. Compound 5 demonstrated inhibitory activities toward human renin (IC50 = 0.9 nM) and human and monkey PRA (IC50 = 1.9 and 6.3 nM, respectively). Oral administration of single doses of 3 and 10 mg/kg of 5 in cynomolgus monkey on pretreatment with furosemide led to dose-dependent significant reductions in ex vivo PRA and sustained lowering of mean arterial blood pressure for more than 12 h.

We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P3-sparing S1P1 agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC50 value of 3.4 nM for human S1P1, and over 5800-fold selectivity against S1P3. In rat on host versus graft reaction (HvGR), the ID50 value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria.

S1P(3)-sparing S1P(1) agonists have attracted attention as a suppressant of autoimmunity with reduced side effects. Our synthetic efforts and extensive SAR studies led to the discovery of 10b named CS-2100 with the EC(50) value of 4.0 nM for human S1P(1) and over 5000-fold selectivity against S1P(3). The in vivo immunosuppressive efficacy was evaluated in rats on host versus graft reaction and the ID(50) value was determined at 0.407mg/kg. The docking studies of CS-2100 with the homology model of S1P(1) and S1P(3) showed that the ethyl group on the thiophene ring of CS-2100 was sterically hindered by Phe263 in S1P(3), not in the case of Leu276 in S1P(1). This observation gives an explanation for the excellent S1P(3)-sparing characteristic of CS-2100.

甘藷を原料とした機能性食品の整腸効果について調べたところ, 次の知見が得られた。 (1)排便回数はprobiotics IMOを摂食した場合, 増加する傾向がみられ, 特に便秘傾向者ではその傾向が強かった。排便量に関してはprobiotics IMOを摂食することにより, 増加する傾向がみられ, 特に便秘傾向者ではその傾向が強かった。 (2)便の色調ではprobiotics IMOを摂食することにより, 黄色化する傾向がみられ, 便秘傾向者ではその傾向が強かった。それは便が酸性に傾き, 便が黄色味を帯びたものと考えられる。便臭ではprobiotics IMOを摂食することにより, 弱くなる傾向がみられ, 排便後の爽快感は改善される傾向がみられた。 (3)便の形状は項目を「コロコロ状+カチカチ状」「バナナ状+半練り状」「泥状+水状」に分けて解析した。「コロコロ状+カチカチ状」はいずれの被験者でも, probiotics IMOを摂食することにより減少する傾向がみられ, 一方「バナナ状+半練り状」は増加する傾向がみられた。また「泥状+水状」は出現率が低く, 便秘傾向者で1回みられたものの非便秘傾向者ではみられなかった。 (4)蒸し芋とprobiotics IMOについて, 10人の評価者により5段階評価法でおいしさを比較したところ, 前者の評点平均値が3.4に対し, 後者は3.8であった。二つの平均値間の有意性をt検定したところ, p, Experimental results of the effects of the intake of a functional food, derived from sweet potato, on defecation are described. After ingestion, functional food significantly increased the weekly defecation frequency and the defecation output, and the effect was more prominent in constipated subjects. The quality of defecation (color, odor, shape) was also measured and all of the qualities were improved after ingestion, especially in constipated subjects. Although the effect was not significant in the non-constipated adults, there was some tendency of the improvement. In conclusion, ingestion of the functional food derived from sweet potato promoted the defecation frequency as well as the stool quality and increased the stool amount in constipated subjects.

Summary The possibility of characterising the garlic odour in in vitro and in vivo was demonstrated using the newly developed electronic nose, based on an array of metal oxide semiconductor sensors. Two grams of raw and heat-treated garlic, and breath odour after eating 2 g of raw garlic and heat-treated garlic were analysed with an electronic nose. Furthermore, calculation of F-value (odour quality) and S-value (odour strength) demonstrated distinct odour differences between the samples, and that the electronic nose could differentiate between the various garlic associated odours corresponding to the different origins (in vivo or in vitro), or to the different processing (raw or heat-treated). The correlation between gas chromatography and sensory analysis was also discussed in order to identify the volatile compounds in the sample, and to investigate the association with the response of human perception to the samples. Results showed that odour sensor data were easier to obtain and were well correlated with both types of instrument.

In this study, the aroma characteristics of steamed sweet potato were compared with those of apple juice and the difference was clarified by sensory evaluation and odor sensor and electroencephalographic analyses. Although apple juice aroma was evaluated to be pleasant by all seven subjects, the same tendency was not observed for all the subjects on the electroencephalogram. Three subjects were relaxed by apple juice aroma, however no changes in α1and α2wave power were observed for the remaining four subjects. It was concluded that apple juice aroma elicits no unpleasant mood. On the other hand, by smelling steamed sweet potato aroma, α wave power was markedly decreased and a sense of tension [was enhanced]. A significant difference between apple juice aroma and steamed sweet potato aroma was observed on the basis of the changes in α wave power. It was clarified that steamed sweet potato aroma is different from apple juice aroma, and is not as pleasant as apple juice aroma.

The mechanism and efficiency of three types of deodorants, namely activated carbon (AC), maltosyl cyclodextrin (MCD) and apple polyphenol (AP), in reducing the “boiled heavy odour” of saccharified sweet potato juice was investigated. The highest deodorising efficiency of AC, followed by MCD and AP, was confirmed by using the electronic nose and sensory analysis. Furthermore, flavour compounds in the sweet potato juice were identified by GC–MS analysis. While AC decreased the peak intensities of all the compounds to below the minimum detection limit, MCD, which eliminated the odour components by the formation of enclosure compounds, did not reduce the peak intensities to a similar extent. The mechanisms of adsorption with AC and envelopment with MCD for the identified odour components of sweet potato juice was also clarified.

The deodorizing effect of the mushroom (Agaricus bisporus) extract on the malodor produced after garlic consumption was investigated using an electronic sensor and sensory evaluation measurements. Comparative gas chromatography analysis revealed that the quantity of methane- and allylthiols that were usually found after garlic solution rinse, significantly fell after mushroom extract rinsing. Furthermore, in-vitro analysis (mixing the garlic solution and mushroom extract) showed that the methanethiol reaction with the mushroom extract proceeded faster than that of the allylthiol. Ab initio calculations implicated an addition reaction as the possible mechanism between the thiol compounds and the polyphenols. In comparison to the methanethiol, the higher activation energy required by allylthiol for a feasible reaction path way with the model acceptor, o-quinone, is expected to contribute to the difference in the rate of the reaction.

A novel class of NaV1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine 9o showed potent human and mouse NaV1.7 inhibitory activities with fair subtype selectivity over NaV1.5. Compound 9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin.

The range of scores elicited by a structured, an unstructured and a 'labels-only' version of the 9-point hedonic scale were compared using consumers from USA, Japan and Korea. It was found that the unstructured scale elicited a wider range of scores for American and Japanese consumers. After correction for hedonic ranges, it was found that Japanese had smaller ranges of scores on all three scales, although the effect was less pronounced for the unstructured scale. The Korean consumers were the exception. Their ranges were less than Americans but their ranges on the unstructured scale did trot increase. The results were discussed in terms of the effects of inhibition of use of categories by the scale labels, effects of translation from the English, psychophysical style and order effects.

BACKGROUND Oncogenic RAS mutants such as v-Ha-RAS activate members of Rac/CDC42-dependent kinases (PAKs) and appear to contribute to the development of more than 30% of all human cancers. PAK1 activation is essential for oncogenic RAS transformation, and several chemical compounds that inhibit Tyr kinases essential for the RAS-induced activation of PAK1 strongly suppress RAS transformation either in cell culture or in vivo (nude mice). Although we have developed a cell-permeable PAK-specific peptide inhibitor called WR-PA18, so far no chemical (metabolically stable) compound has been developed that directly inhibits PAK1 in a highly selective manner. Thus, we have explored such a PAK1 inhibitor(s) among synthetic derivatives of an adenosine triphosphate antagonist. RESULTS From the naturally occurring adenosine triphosphate antagonist K252a, we have developed two bulky derivatives, called CEP-1347 and KT D606 (a K252a dimer), which selectively inhibit PAKs or mixed-lineage kinases both in vitro and in cell culture and convert v-Ha-RAS-transformed NIH 3T3 cells to flat fibroblasts similar to the parental normal cells. Furthermore, these two K252a analogues suppress the proliferation of v-Ha-RAS transformants, but not the normal cells. CONCLUSION These bulky adenosine triphosphate antagonists derived from K252a or related indolocarbazole compounds such as staurosporine would be potentially useful for the treatment of RAS/ PAK1-induced cancers, once their anti-PAK1 activity is significantly potentiated by a few additional chemical modifications at the sugar ring suggested in this paper.

This letter describes syntheses of (−)-(7S)-and (+)-(7R)-K252a dimers wherein a convergent bis-indole-N-glycosidic coupling step was used for the resolution of the C(7) substituted (±)-aglycon. Dimerization of the derived monomers was achieved via olefin methathesis.

A key obstacle to developing automated histopathology assessment tools is the difficulty of defining quantifiable image features that could serve as fundamental data elements capable of distinguishing key disease types and subtypes. A variety of feature extraction and selection methods for histology images have been proposed. However, comparisons of different feature descriptor approaches remains challenging because of varying datasets and emphases chosen by different authors. As an example of how a shared reference atlas could accelerate efforts in this area. In this study, we constructed normal and disease sample datasets by standardizing histology images employed from Allen Brain Atlas. After preparing the datasets, we extracted features mentioned in the preceding studies from the datasets to characterize normal and disease tissues. To confirm statistical significance between the normal and disease images, Kolmogorov-Smirnov test was employed. The experimental results indicated that topological features are effective to distinguish the normal images from the disease ones. This paper also shows the details of construction of the datasets, segmentation of nuclei, feature descriptors and the experimental results. We discuss the effectiveness and generalizability of derived features.

Three-dimensional models of the gelatinase catalytic domains were built from collagenase structures by the homology modeling technique. The docking of different types of inhibitors was then studied in an attempt to obtain structural insight into their binding modes. In the case of an amide compound docked with gelatinase A, almost the same binding mode was obtained as that observed in the crystal structure of another amide compound complexed with collagenase. With respect to our series of matlystatin analogs, the key hydrogen bonding and hydrophobic interactions with gelatinase B were similar to those of the above amide compounds, although these derivatives have a unique piperazine ring. The length and hydrophobic nature of the S1' subsite was well consistent with the observation that the inhibitory activity rises as the alkyl chain at P1' becomes longer. The binding mode of a sulfonamide inhibitor was slightly different from that of amide and piperazine inhibitors, but similar to that proposed recently for another sulfonamide inhibitor.

During carcinogenesis of pancreatic islets in transgenic mice, an angiogenic switch activates the quiescent vasculature. Paradoxically, vascular endothelial growth factor (VEGF) and its receptors are expressed constitutively. Nevertheless, a synthetic inhibitor (SU5416) of VEGF signalling impairs angiogenic switching and tumour growth. Two metalloproteinases, MMP-2/gelatinase-A and MMP-9/gelatinase-B, are upregulated in angiogenic lesions. MMP-9 can render normal islets angiogenic, releasing VEGF. MMP inhibitors reduce angiogenic switching, and tumour number and growth, as does genetic ablation of MMP-9. Absence of MMP-2 does not impair induction of angiogenesis, but retards tumour growth, whereas lack of urokinase has no effect. Our results show that MMP-9 is a component of the angiogenic switch.

R-94138, a matrix metalloproteinase inhibitor, was examined for the ability to prevent peritoneal dissemination of a human gastric cancer xenograft, TMK-1. When the supernatant of a co-culture of TMK-1 cells and human normal fibroblast cells was subjected to gelatin zymography, it was clear that the protein expression of MMP-2 had been inhibited by R-94138. When TMK-1 was injected intraperitoneally (i.p.) into nude mice at 5 x 10(5) cells/body, the resulting peritoneal dissemination mimicked clinical carcinomatous peritonitis. When the maximum tolerated dose of mitomycin C (MMC) or cisplatin (DDP) was given 12 h after the tumor inoculation, peritoneal dissemination was completely inhibited, while the effect of R-94138 was limited when it was given i.p. at a dose of 20 mg/kg in a schedule of q.d. x 5 starting 12 h after tumor injection. MMC and DDP also suppressed peritoneal dissemination when they were administered 1 week after the tumor inoculation at a single dose of 2 and 3 mg/kg i.p., respectively. R-94138 inhibited peritoneal dissemination when it was administered i.p. at a dose of 30 mg/kg in a schedule of q.d. x 5 starting from 1 week after tumor injection. The combination of MMC and R-94138 increased the preventive effect on peritoneal dissemination. R-94138 seems to be a promising candidate to prevent peritoneal dissemination of gastric cancer.

We report synthesis and optimization of a series of (3 S ,5 R )-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as renin inhibitors. Chemical modification of P 1 ′ P 1 ′ , P 2 ′ P 2 ′ and P 3 portions led to a promising 3,5-disubstituted piperidine 32o showing high renin inhibitory activity and favorable oral exposure in both rats and cynomolgus monkeys with acceptable CYP and hERG current inhibition. Compound 32o exhibited a significant blood pressure lowering effect by oral administration in two hypertensive animal models, double transgenic rats and furosemide pretreated cynomolgus monkeys.

With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure–activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h.

Utilizing X-ray crystal structure analysis, (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides were designed and identified as renin inhibitors. The most potent compound 15 demonstrated favorable pharmacokinetic and pharmacodynamic profiles in rat.

Introduction of the 2,2-dimethyl-4-phenylpiperazin-5-one scaffold into the P(3)-P(1) portion of the (2S,4S,5S)-5-amino-6-dialkylamino-4-hydroxy-2-isopropylhexanamide backbone dramatically increased the renin inhibitory activity without using the interaction to the S(3)(sp) pocket. Compound 31 exhibited >10,000-fold selectivity over other human proteases, and 18.5% oral bioavailability in monkey.

We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P(3)-sparing S1P(1) agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3. Extensive SAR studies led to the finding of 1,3-thiazole 24c with the EC(50) value of 3.4 nM for human S1P(1), and over 5800-fold selectivity against S1P(3). In rat on host versus graft reaction (HvGR), the ID(50) value of 24c was determined at 0.07 mg/kg. The pharmacokinetics in rat and monkey is also reported. Compared to compound 3, 24c showed excellent stability against enterobacteria.

The first total synthesis of matlystatin B (1a), a low molecular weight inhibitor of type IV collagenases, was accomplished, and its absolute configuration was unambiguously determined. Furthermore, ten stereoisomers of 1a were synthesized, and the inhibition of the 92 kDa type IV collagenase and of other metalloproteinases by each stereoisomer was investigated.

Modulators of sphingosine phosphate receptor-1 (S1P(1)) have recently been focused as a suppressant of autoimmunity. We have discovered a 4-ethylthiophene-based S1P(1) agonist 1-({4-Ethyl-5-[5-(4-phenoxyphenyl)-1,2,4-oxadiazol-3-yl]-2-thienyl}methyl)azetidine-3-carboxylic acid (CS-2100, 8) showing potent S1P(1) agonist activity against S1P(3) and an excellent in vivo potency. We report herein the synthesis of CS-2100 (8) and pharmacological effects such as S1P(1) and S1P(3) agonist activity in vitro, peripheral blood lymphocyte lowering effects and the suppressive effects on adjuvant-induced arthritis and experimental autoimmune encephalomyelitis (EAE) in animal models. The pharmacokinetic data were also reported. CS-2100 (8) had >5000-fold greater agonist activity for human S1P(1) (EC(50); 4.0 nM) relative to S1P(3) (EC(50); >20,000 nM). Following administration of single oral doses of 0.1 and 1 mg/kg of CS-2100 (8) in rats, lymphocyte counts decreased significantly, with a nadir at 8 and/or 12 h post-dose and recovery to vehicle control levels by 24-48 h post-dose. CS-2100 (8) is efficacious in the adjuvant-induced arthritis model in rats (ID(50); 0.44 mg/kg). In the EAE model compared to the vehicle-treated group, significant decreases in the cumulative EAE scores were observed for 0.3 and 1 mg/kg CS-2100 (8) groups in mice. While CS-2100 (8) showed potent efficacy in various animal disease models, it was also revealed that the central 1,2,4-oxadiazole ring of CS-2100 (8) was decomposed by enterobacteria in intestine of rats and monkeys, implicating the latent concern about an external susceptibility in its metabolic process in the upcoming clinical studies.

Of the five congeners in the matlystatin series, matlystatin A ( 1 ) is the most potent inhibitor of type IV collagenases. The total synthesis of 1 was accomplished, and the absolute configuration was unambiguously determined as shown in figure I.

Of the five congeners in the matlystatin series, matlystatin A ( 1 ) is the most potent inhibitor of type IV collagenases. The total synthesis of 1 was accomplished, and the absolute configuration was unambiguously determined as shown in figure I.

To investigate a series of new inhibitors of gelatinases based on matlystatin B (1b), extensive structure-activity relationship studies were performed. The new derivatives were evaluated in vitro for the ability to inhibit gelatinases.The inhibitory activities against thermolysin were also assayed to test the compounds' selectivity. Among the compounds modified at the P'3 moiety, the N-methylamide derivative 5 g was virtually twice as effective on gelatinase B as the parent compound 1b (5g, IC50=0.27μM vs. 1b, IC =0.57μM). Other derivatives, including 1) esters 7a and 7b having the ester portions P'2 and P'3, 2) the cyclic amino acids, L-proline or L-pipecolinic acid (13a and 13b) bearing P'2, and 3) compounds 29a and 29b representing an attachment of the pentyl side chain at C3' (P'1 side chain)instead of C2', all showed decreased potencies. The key discovery was the observation that the introduction of a nonyl group at the P'1 position yielded a compound (31f, IC =0.0012μM) with high inhibitory activity against gelatinases and high selectivity over thermolysin. This result suggested that the S'1 subsites of the gelatinases have a locally deep hydrophobic structure, since on the basis of the optimum inhibitory activity in the alkyl series, the nonyl group seems to fit best into this hydrophobic pocket. Thus 31f exhibited a 475-fold more potent inhibitory activity than 1b towards gelatinase B.

For the purpose of reducing the strong CYP3A4 inhibitory potency of diamide prodrug 4, cyclic prodrugs of tricyclic-based FBPase inhibitors were synthesized. Extensive SAR studies led to the discovery of pyridine-containing cyclic prodrug 20, which strongly inhibited glucose production in monkey hepatocytes and also showed weak CYP3A4 inhibitory potency.

An efficient and highly stereoselective total synthesis of the natural product (+/-)-welwitindolinone A isonitrile (1) is described. The bicyclo[4.2.0]octane core of 1 was established by a regio- and diastereoselective [2+2] ketene cycloaddition. The C12 quaternary center and vicinal stereogenic chlorine were installed in a single operation with excellent stereocontrol via a chloronium ion mediated semipinacol rearrangement. Described strategies for construction of the spiro-oxinole include a SmI2-LiCl mediated reductive cyclization and a novel anionic cyclization that simultaneously constructs the spiro-oxindole and vinyl isonitrile moieties.

The complete carbon skeleton of welwitindolinone A isonitrile has been prepared by using a [2+2] cycloaddition to establish the bicyclo[4.2.0]octane core and a SmI2-mediated intramolecular reductive cyclization between an enone and an aryl isocyanate to stereoselectively install the spiro-oxindole (see scheme; DBU=1,8-diazabicyclo[5.4.0]undec-7-ene).

Recent efforts in our laboratories have resulted in a synthetic approach toward C2‘-alkylated K252a analogues via extension of a K252a cyclofuranosylation strategy. The bis-indole-N-glycosidic coupling of 6-N-(3,4-dimethoxybenzyl)-staurosporinone (21) with a number of highly functionalized carbohydrates has given access to previously unattainable, biologically relevant analogues.

To investigate a series of new inhibitors of gelatinases based on matlystatin B (1b), extensive structure-activity relationship studies were performed. The new derivatives were evaluated in vitro for the ability to inhibit gelatinases. The inhibitory activities against thermolysin were also assayed to test the compounds' selectivity. Among the compounds modified at the P'3 moiety, the N-methylamide derivative 5 g was virtually twice as effective on gelatinase B as the parent compound 1b (5g, IC50 = 0.27 microM vs. 1b, IC50 = 0.57 microM). Other derivatives, including 1) esters 7a and 7b having the ester portions P'2 and P'3, 2) the cyclic amino acids, L-proline or L-pipecolinic acid (13a and 13b) bearing P'2, and 3) compounds 29a and 29b representing an attachment of the pentyl side chain at C3' (P'1 side chain) instead of C2', all showed decreased potencies. The key discovery was the observation that the introduction of a nonyl group at the P'1 position yielded a compound (31f, IC50 = 0.0012 microM) with high inhibitory activity against gelatinases and high selectivity over thermolysin. This result suggested that the S'1 subsites of the gelatinases have a locally deep hydrophobic structure, since on the basis of the optimum inhibitory activity in the alkyl series, the nonyl group seems to fit best into this hydrophobic pocket. Thus 31f exhibited a 475-fold more potent inhibitory activity than 1b towards gelatinase B.

The structures of matlystatins, novel type IV collagenase inhibitors isolated from Actinomadura atramentaria, have been determined by a systematic application of homo- and heteronuclear 2D NMR and FAB-MS/MS techniques. Their structures were characterized by the presence of piperazic acid and hydroxamic acid moieties, structural motifs often seen in protease inhibitors.

Hauptmann's periplanone A and its stereoisomer as a racemic form have been synthesized from germacrene-D in 8 steps. On the basis of male electroantennogram (EAG) responses, the former has been proved to enter into the periplanone A receptor, but not into the periplanone B receptor. The stereoisomer, which has been synthesized by Macdonald et al., shows no EAG response. Finally, acid-catalyzed cyclization of Hauptmann's periplanone A has not afforded Persoons' periplanone A, but the known hydroazulenone.