Relative stereochemical determination of the C61–C83 fragment of symbiodinolide using a stereodivergent synthetic approach

Structural determination is required in the use of marine natural products to create novel drugs and drug leads in medicinal chemistry. Symbiodinolide, which is a polyol marine natural product with a molecular weight of 2860, increases the intracellular Ca2+ concentration and exhibits inhibitory activity against cyclooxygenase-1. Seventy percent of the structure of symbiodinolide has been stereochemically clarified. Herein, we report the elucidation of the relative configuration of the C61–C83 fragment, which is among the remaining thirty percent, using a stereodivergent synthetic strategy. We first assigned the relative configuration of the C61–C74 fragment. Two candidate diastereomers of the C61–C74 fragment were synthesized, and their NMR data were compared with those of the natural product, revealing the relative stereochemistry of this component. We then narrowed down the candidate compounds for the C69–C83 fragment from 16 possible diastereomers by analyzing the NMR data of the natural product, and we thus selected eight candidate diastereomers. Stereodivergent synthesis of the candidates for this fragment and comparison of the NMR data of the natural product and the eight synthetic products resulted in the relative stereostructural clarification of the C69–C83 fragment. These individually determined relative stereochemistries of the C61–C74 and C69–C83 fragments were connected via the common C69–C73 tetrahydropyran moiety of the fragments. Finally, the relative configuration of the C61–C83 fragment of symbiodinolide was determined. The stereodivergent synthetic approach used in this study can be extended to the stereochemical determination of other fragments of symbiodinolide

ゲンダイ GP タイケン ゼミ ヨシノガワ ゲンリュウ ノ シゼン ト ブンカ オ ミテ シッテ カンガエテミル : ゲンダイ GP ホウジョウナ ヨシノガワ オ ジゾク カノウ トスル キョウセイ カンキョウ キョウイク ノ イッカン トシテ

吉野川は、その流域に豊穣な土地を生み出し、藍作により地域産業の基盤が築かれて発展してきた。 これまでの現代GP体験ゼミでは、吉野川下流域の自然を利用した地域文化の歴史的意義を体験して考 える目的で、吉野川第十堰の改築問題、藍作と食文化、下流域の植生と水生昆虫の生息などを取り上げ てきた。この取組の結果、徳島の文化の基盤が吉野川の自然の思恵を受けて築かれてきたことに関して、 体験を通して考えるきっかけを提供することができた。今回は、吉野川源流の一つである剣山の植物、 動物の生態と山岳信仰を取り上げ、郷土の自然を体験しながら学びを深めるゼミを実施した。その結果、 野生のカモシカや鹿の生息を直接観察することができた。また、鹿の生息域が剣山の稜線近くまで上昇 していることなど、生態系の変動から環境の変異を体験する機会となった。さらに稜線近くに生息して いる鹿が樹木の立ち枯れを起こる原因になっていることを直接目で確かめることが出来た。今回の取組 のような地域の自然をフィールドとした体験型授業の実施は、学生に対して主体的な学びの意義に対す る理解を深めることができることが明らかになった。本稿では、今回の取組の概要を紹介し、その意義 を考察した

Late-stage divergent synthesis and antifouling activity of geraniol-butenolide hybrid molecules

Hybrid molecules consisting of geraniol and butenolide were designed and synthesized by the late-stage divergent strategy. In the synthetic route, ring-closing metathesis was utilized for the construction of a butenolide moiety. A biological evaluation of the eight synthetic hybrid compounds revealed that these molecules exhibit antifouling activity against the cypris larvae of the barnacle Balanus (Amphibalanus) amphitrite with EC50 values of 0.30-1.31 μg mL-1. These results show that hybridization of the geraniol and butenolide structural motifs resulted in the enhancement of the antifouling activity

Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in 40–69-years subjects

[Background] Visceral fat obesity can be defined quantitatively by abdominal computed tomography, however, the usefulness of measuring visceral fat area to assess the etiology of gastrointestinal reflux disease has not been fully elucidated. [Methods] A total of 433 healthy subjects aged 40–69 years (234 men, 199 women) were included in the study. The relationship between obesity-related factors (total fat area, visceral fat area, subcutaneous fat area, waist circumference, and body mass index) and the incidence of reflux erosive esophagitis was investigated. Lifestyle factors and stomach conditions relevant to the onset of erosive esophagitis were also analyzed. [Results] The prevalence of reflux erosive esophagitis was 27.2% (118/433; 106 men, 12 women). Visceral fat area was higher in subjects with erosive esophagitis than in those without (116.6 cm2 vs. 64.9 cm2, respectively). The incidence of erosive esophagitis was higher in subjects with visceral fat obesity (visceral fat area ≥ 100 cm2) than in those without (61.2% vs. 12.8%, respectively). Visceral fat obesity had the highest odds ratio (OR) among obesity-related factors. Multivariate analysis showed that visceral fat area was associated with the incidence of erosive esophagitis (OR = 2.18), indicating that it is an independent risk factor for erosive esophagitis. In addition, daily alcohol intake (OR = 1.54), gastric atrophy open type (OR = 0.29), and never-smoking history (OR = 0.49) were also independently associated with the development of erosive esophagitis. [Conclusions] Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in subjects aged 40–69 years

Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study

[Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676

A New Treatment in Sciaphila (Triuridaceae) in Taiwan and Japan

Sciaphila tosaensis Makino, endemic to Japan, and S. megastyla Fukuy. & T. Suzuki, endemic to Lanyu Island in Taiwan, are regarded to be identical with S. secundiflora Thwaites ex Benth., which is widely distributed in the Pacific islands, Malesia, Hongkong and Sri Lanka