Total Synthesis of Dinorsesquiterpenoid Oxyphyllin A/Belchinoid A.

Here, we report the first synthesis of oxyphyllin A/belchinoid A, a 7,9-seco-8,12-dinor-guaiane sesquiterpene whose isolation was reported independently by two groups in 2023. This synthesis utilizes a key sequential sulfone-mediated intermolecular alkylation/5-endo-tet cyclization reaction to establish the C1, C4, C5 stereocenters. Subsequent transformations, including regio- and stereoselective hydride addition-based desulfonylation via a π-allyl palladium complex and the Wittig reaction with a stable phosphonium ylide, facilitated the synthesis of oxyphyllin A/belchinoid A.

Total Synthesis of Marine Polyketide Plakortone Q.

The total synthesis of the natural bicyclo[3.3.0]furanolactone polyketide, plakortone Q, was achieved in 24 steps from (R)-Roche ester. The main feature of this synthetic strategy is the stereoselective construction of a central tetrahydrofuran moiety with four consecutive stereoisomeric centers using the Upjohn dihydroxylation of oxiranyl-substituted alkenes and acid-mediated 5-endo-tet cyclization.

[A case of hepatic portal venous gas and upper gastrointestinal mucosal injury due to accidental ingestion of hydrogen peroxide].

A 40-year-old woman was admitted to our hospital by ambulance due to accidental ingestion of 100ml of 35% hydrogen peroxide. Although the patient suffered from frequent vomiting, abdominal distension, and abdominal pain, signs of peritonitis were not observed. An abdominal computed tomography examination demonstrated obvious gas images in the gastric wall and intrahepatic portal veins. Upper gastrointestinal endoscopy revealed mucosal redness, swelling, and erosion from the lower part of the esophagus to the duodenum. Portal venous gas and upper gastrointestinal mucosal injury due to accidental hydrogen peroxide ingestion were suspected. As the vital signs were stable and there were no signs peritoneal irritation or neurological symptoms, she was treated medically with vonoprazan, rebamipide, and sodium alginate. The next day, abdominal symptoms immediately improved and 3 days later, hepatic portal venous gas had disappeared on ultrasonography. She was discharged on the 5th day after admission. Two months later, upper gastrointestinal endoscopy showed improvement in inflammatory findings. We report a remarkable case of hepatic portal venous gas and upper gastrointestinal mucosal injury and elucidate the endoscopic findings associated with hydrogen peroxide ingestion.

Biomimetic total synthesis of plakortone Q via acid-mediated tandem cyclization.

Plakortone Q and plakdiepoxide are natural polyketides isolated from the marine sponge Plakortis simplex. Bicyclo[3.3.0]furanolactone compounds, including plakortone Q, are expected to exhibit a wide range of pharmacological activities. Therefore, developing a simple and versatile synthetic method to produce these compounds is an important research goal. We have achieved the first total synthesis of plakortone Q and plakdiepoxide through an efficient protecting-group-free strategy. The key transformation was an acid-mediated tandem 5-endo-tet/5-endo-tet cyclization of vicinal diepoxide to build the tetrahydrofuran-γ-lactone motif.

Total Synthesis of Chlorinated Oxylipin Eiseniachloride B.

Eiseniachloride B is a marine chlorinated oxylipin isolated from the brown alga Eisenia bicyclis. This natural product contains cyclopentane, chlorohydrin, and 14-membered lactone systems that incorporate five stereogenic centers. In this paper, we report on the total synthesis of structurally unique oxylipin eiseniachloride B from optically active lactol via ecklonialactone B in a linear sequence comprising 11 steps with a 12.1% overall yield.

Total Synthesis of ent-Ascospiroketal B.

Ascospiroketal B was isolated from a marine-derived fungus as a structurally unique polyketide possessing a rare tricyclic core including 5,5-spiroketal-γ-lactone. An asymmetric total synthesis of ent-ascospiroketal B was achieved using an original synthetic route. The synthesis included the stereoselective construction of 5,5-spiroketal for ascospiroketal B and stereocontrolled construction of a quaternary asymmetric carbon by rearrangement of a trisubstituted epoxide.

Formal synthesis of cis-solamin: acid-catalyzed one-step construction of 2,5-disubstituted tetrahydrofuran.

A divergent strategy has been used for the concise and efficient enantioselective formal synthesis of Annonaceous acetogenin cis-solamin. Our synthetic strategy comprises concise preparation of the diepoxyester via an 11-membered silaketal constructed by ring-closing metathesis after the dimerization of chiral epoxides, and uses an acid-catalyzed tandem intramolecular SN2-like reaction to construct the threo-cis-threo configuration of the tetrahydrofuran-diol moiety.

Phellilane L, Sesquiterpene Metabolite of Phellinus linteus: Isolation, Structure Elucidation, and Asymmetric Total Synthesis.

A new cyclopropane-containing sesquiterpenoid, phellilane L (1), was isolated from the medicinal mushroom Phellinus linteus ("Meshimakobu" in Japanese), a member of the Hymenochaetaceae family and a well-known fungus that is widely used in East Asia. The planar structure of 1 was determined on the basis of spectroscopic analysis. The authors achieved the first total synthesis of 1. Our protecting group-free synthesis features a highly stereoselective one-pot synthesis involving an intermolecular alkylation/cyclization/lactonization strategy for construction of the key cyclopropane-γ-lactone intermediate. Additionally, our synthesis determined the absolute configuration of phellilane L (1).

Smoking and prevalence of nocturia in Japanese patients with type 2 diabetes mellitus: a post-hoc analysis of The Dogo Study.

AIMS: No evidence exists regarding the association between smoking status and nocturia among patients with type 2 diabetes mellitus. We evaluated this association among Japanese patients with type 2 diabetes mellitus by post-hoc analysis. METHODS: Study subjects were 817 Japanese patients with type 2 diabetes mellitus. Study subjects were considered to have nocturia if they answered "once or more" to the question: "Within one week, how many times do you typically wake up to urinate from sleeping at night until waking in the morning?" We used the following three outcomes: (1) nocturia was ≥1 voids per night; (2) moderate nocturia was ≥2 voids per night; and (3) severe nocturia was ≥3 voids per night. Adjustments were made for age, sex, body mass index, hypertension, dyslipidemia, stroke, glycated hemoglobin, current drinking, use of anti-hypertensive agent, use of insulin, use of oral anti-hyperglycemic agent, and diabetic retinopathy. RESULTS: The prevalence values of one void per night, two voids per night, and three or more voids per night were 39.5%, 27.1%, and 14.8%, respectively. Current smoking was independently inversely associated with severe nocturia compared with never or former smoking; the adjusted PR was 0.47 (95%CI: 0.25-0.89). Among the 443 patients who had ever smoked, compared with former smoking, current smoking was independently inversely related to severe nocturia; the adjusted PR was 0.44 (95%CI: 0.24-0.82). CONCLUSIONS: In Japanese patients with type 2 diabetes mellitus, current smoking may be independently inversely associated with severe nocturia.

B-type natriuretic peptide and renal function in Japanese patients with type 2 diabetes mellitus: The Dogo Study.

Among patients with type 2 diabetes mellitus, the association between B-type natriuretic peptide (BNP) and renal function remains controversial. We therefore investigated this issue among Japanese patients with type 2 diabetes mellitus. This study included 687 Japanese patients with type 2 diabetes mellitus. BNP levels were divided at quartile points on the basis of the distribution. We used four outcomes regarding the renal function: 1) chronic kidney disease (CKD): estimated glomerular filtration rate (eGFR) < 60ml/min/1.72m2, 2) advanced CKD: eGFR < 30ml/min/1.72m2, 3) microalbuminuria: urinary albumin creatinine ratio (UACR) ≥ 30 mg/g creatinine, and 4) macroalbuminuria: UACR ≥ 300 mg/g creatinine. The prevalence values of CKD, advanced CKD, microalbuminuria, and macroalbuminuria were 27.4％, 2.5%, 31.4%, and 9.3%, respectively. Highest BNP (≥ 39.2 ng/ml) was independently positively associated with microalbuminuria and macroalbuminuria (adjusted ORs, 2.61 [95% CI: 1.53-4.49] and 3.45 [95% CI: 1.46-8.72], respectively). High BNP was not associated with advanced CKD or CKD. There was a statistically significant positive exposure-response relationships between the BNP level and advanced CKD, microalbuminuria, and macroalbuminuria (p for trend = 0.047, 0.001, and 0.003, respectively). BNP level may be independently positively associated with advanced CKD, microalbuminuria, and macroalbuminuria but not CKD in Japanese patients with type 2 diabetes mellitus.

Microvascular complications and prevalence of urgency incontinence in Japanese patients with type 2 diabetes mellitus: The dogo study.

AIMS: Diabetes was significantly positively associated with urgency incontinence in several epidemiological studies. We examine the association between diabetic neuropathy, which we defined based on neuropathic symptoms, the absence of the Achilles reflex, and/or abnormal vibration perception, and urgency incontinence among Japanese patients with type 2 diabetes mellitus. METHODS: Study subjects were 742 Japanese patients with type 2 diabetes mellitus, aged 19-70 years, who had undergone blood tests at our institutions. A self-administered questionnaire was used to collect information on the variables under study. Urgency incontinence was defined as present when a subject answered "once a week or more" to the question: "Within one week, how often do you leak urine because you cannot defer the sudden desire to urinate ?". Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, the absence of the Achilles reflex, and/or abnormal vibration perception. Adjustment was made for sex, age, body mass index, duration of type 2 diabetes mellitus, current smoking, hypertension, dyslipidemia, glycated hemoglobin, stroke, coronary artery disease, insulin therapy, diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. RESULTS: The prevalence of urgency incontinence was 8.6%. Diabetic neuropathy was independently positively associated with urgency incontinence: the adjusted OR was 2.20 (95%CI: 1.16-4.36). Associations between diabetic retinopathy or nephropathy and the prevalence of urgency incontinence were not significant. CONCLUSIONS: In Japanese patients with type 2 diabetes mellitus, only diabetic neuropathy was independently positively associated with urgency incontinence. Neurourol. Urodynam. 35:1024-1027, 2016. © 2015 Wiley Periodicals, Inc.

Amitorines A and B, Nitrogenous Diterpene Metabolites of Theonella swinhoei: Isolation, Structure Elucidation, and Asymmetric Synthesis.

Two new nitrogenous prenylbisabolanes never before found in Lithistid sponges have been isolated from Theonella swinhoei. These new diterpenes, named amitorine A (1) and amitorine B (2), containing a prenylbisabolane skeleton have been characterized by spectroscopic analyses, and the relative and absolute configurations of 1 and 2 were determined by asymmetric synthesis of both diastereomers via the common bicyclic lactone 6 intermediate.

Age and Prevalence of Esophageal Reflux Disease in Japanese Patients with Type 2 Diabetes Mellitus: The Dogo Study.

BACKGROUND: Only limited epidemiological evidence exists regarding the relationship between age and gastroesophageal reflux disease (GERD) among Japanese patients with type 2 diabetes mellitus. AIM: The purpose of the present study is to investigate this issue among Japanese patients with type 2 diabetes mellitus. METHODS: A multicenter cross-sectional study was conducted in 847 Japanese patients with type 2 diabetes mellitus. Subjects were divided into quartiles according to age: (1) 19 ≤ age < 56, (2) 56 ≤ age < 64, (3) 64 ≤ age < 71, and (4) 71 ≤ age < 89. GERD was defined as present when a subject had a Carlsson-Dent self-administered questionnaire (QUEST) score ≥4. RESULTS: The prevalence of GERD was 31.5 %. Younger age was independently associated with a higher prevalence of GERD: the adjusted odds ratios (95 % confidence intervals) for GERD in relation to age < 56, 56 ≤ age < 64, 64 ≤ age < 71, and ≥71 were 3.73 (2.16-6.53), 1.98 (1.21-3.27), 1.66 (1.05-2.68), and 1.00 (reference), respectively (P for trend = 0.001). Among 201 patients with PPI or histamine H2-receptor antagonist (H2RA), less than 56 years of age was independently positively associated with GERD: the adjusted OR was 5.68 (95 % CI 1.55-22.18) (P for trend = 0.02). CONCLUSIONS: Younger age may be independently positively associated with GERD among Japanese type 2 diabetes mellitus patients, regardless of the use of PPI or H2RA.

Association between subclinical hypothyroidism and diabetic nephropathy in patients with type 2 diabetes mellitus.

Subclinical hypothyroidism (SCH) has been associated with type 2 diabetes mellitus. However, it is unknown whether common complications of type 2 diabetes, such as diabetic nephropathy, are also present with SCH. Here, we investigated the association between SCH and diabetic nephropathy among Japanese patients with type 2 diabetes mellitus. In this multicenter cross-sectional study, we recruited 414 such patients who had no previous history of thyroid disease. Serum thyroid hormone levels and the urinary albumin:creatinine ratio were measured. SCH was defined as an elevated thyroid-stimulating hormone (TSH) level (>4.0 mIU/L), and diabetic nephropathy was defined as urinary albumin/creatinine ratio ≥300 mg/g. The prevalence of SCH was 8.7% (n = 36) among patients with type 2 diabetes mellitus. The SCH group had a higher prevalence of dyslipidemia (p = 0.008) and diabetic nephropathy (p = 0.014) than the euthyroid group. Multivariate analysis identified significant positive associations between diabetic nephropathy and SCH (odds ratio [OR], 3.51; 95% confidence interval [CI], 1.10-10.0; p = 0.034), hypertension (OR, 4.56; 95% CI, 1.69-14.7; p = 0.001), and smoking (OR, 3.02; 95% CI, 1.14-7.91; p = 0.026). SCH may be independently associated with diabetic nephropathy in Japanese patients with type 2 diabetes mellitus.

Cordyceps militaris fruit body activates myeloid dendritic cells via a Dectin-1-mediated pathway.

Cordyceps militaris, an entomopathogenic fungus, has been traditionally used in East Asian medicine. Recent research indicates that the fruit bodies of C. militaris are rich in bioactive compounds, such as polysaccharides and nucleosides, which may offer health benefits. However, the specific components responsible for its immunostimulatory effects and the mechanisms involved remain unclear. This study explored the immunomodulatory activity of a fruit body extract from C. militaris, named Ryukyu-kaso (RK), and examined the effect of the ß-glucan receptor Dectin-1 on bone marrow-derived dendritic cells (BMDCs). Our results demonstrated that RK, which contains 1,3-ß-glucan, effectively stimulated BMDCs to secrete pro-inflammatory and immunoregulatory cytokines and upregulated surface markers indicative of maturation and activation. Notably, these immunostimulatory effects were completely absent in BMDCs derived from Dectin-1-knockout mice, confirming that Dectin-1 is crucial for RK-induced immunomodulation. These findings provide new insights into the immunostimulatory mechanisms of C. militaris and underscore the potential of RK as a natural immunomodulatory agent for various therapeutic applications.

One-pot synthesis of phenol derivatives by the novel intramolecular Alder-Rickert reaction: effects of aryl substituent at the 3-position of cyclohexenone derivatives on reactivity.

We examined In(OTf)3-catalyzed enolization and intramolecular Alder-Rickert reactions of cyclohexenone derivatives. The 3-aryl substituted cyclohexenone derivatives bearing an ethoxycarbonyl-substituted alkyne moiety could be converted into the corresponding phenols in comparatively good yield.

Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds.

MGB polyamide-oligonucleotide conjugates ON 1-4 with linked MGB polyamides at the 2-exocyclic amino group of a guanine base using aminoalkyl linkers were synthesized and evaluated in terms of binding affinity for complementary DNA containing the MGB polyamide binding sequence using T m and CD analyses. The MGB polyamides comprised pyrrole polyamides (Py4- and Py3-), which possess binding affinity for A-T base pairs, and imidazole (Im3-) and pyrrole-γ-imidazole (Py3-γ-Im3-) polyamide hairpin motifs, which possess binding affinity for C-G base pairs. It was found that the stability of modified dsDNA was greatly influenced by the linker length. Py4- and Py3-oligonucleotide conjugates (ON 1 (n = 4) and ON 2 (n = 4)) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA. Although Im3-oligonucleotide conjugate ON 3 (n = 4) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA, stabilization of dsDNA by the imidazole amide moiety of ON 3 (n = 4) was lower compared with the pyrrole amide moiety of ON 2 (n = 4). The Py3-γ-Im3-oligonucleotide conjugate ON 4 (n = 2), which possesses binding affinity for C-G base pairs via a pyrrole/imidazole combination and contains a 2-aminoethyl linker, showed high binding ability for complementary DNA. Furthermore, the DNA sequence recognition of MGB polyamide-oligonucleotide conjugates was investigated using single-base mismatch DNAs, which possess a mismatch base in the MGB polyamide binding sequence. The Py3-γ-Im3-oligonucleotide conjugate ON 4 (n = 2) showed high sequence recognition ability for complementary DNA.

Total synthesis of marine eicosanoid (-)-hybridalactone.

(-)-Hybridalactone (1) is a marine eicosanoid isolated from the red alga Laurencia hybrida. This natural product contains cyclopropane, cyclopentane, 13-membered macrolactone and epoxide ring systems incorporating seven stereogenic centers. Moreover, this compound has an acid-labile skipped Z,Z-diene motif. In this paper, we report on the total synthesis of (-)-hybridalactone (1). The unique eicosanoid (-)-hybridalactone (1) was synthesized starting from optically active γ-butyrolactone 2 in a linear sequence comprising 21 steps with an overall yield of 21.9%. A key step in the synthesis of (-)-hybridalactone (1) is the methyl phenylsulfonylacetate-mediated one-pot synthesis of the cis-cyclopropane-γ-lactone derivative. This reaction provided an efficient and stereoselective access to cis-cyclopropane-γ-lactone 12. Further elaboration of the latter compounds through desulfonylation, epoxidation, oxidation, Wittig olefination and Shiina macrolactonization afforded (-)-hybridalactone.

Synthesis of phenol derivatives from cyclohex-2-enones bearing an alkyne through Lewis acid-catalyzed enolization and intramolecular Alder-Rickert reaction.

A cationic rhodium(I) complex- or In(OTf)(3)-catalyzed synthesis of phenol derivatives from cyclohex-2-enone having an ethoxycarbonyl-substituted alkyne has been achieved. This reaction proceeds via enolization and an intramolecular Alder-Rickert reaction.

Synthesis of marine diterpene isocyanide (-)-kalihinol Y and diterpene isothiocyanate (-)-10-epi-kalihinol I.

The authors described the first synthesis of diterpene isocyanide (-)-kalihinol Y and diterpene isothiocyanate (-)-10-epi-kalihinol I from synthetic intermediates of kalihinol A. The absolute structures of these compounds were confirmed by these syntheses.