Total synthesis and complete configurational assignment of amphirionin-2

Amphirionin-2 is a linear polyketide metabolite that exhibits potent and selective cytotoxic activity against certain human cancer cell lines. We disclose herein the first total synthesis of amphirionin-2 and determination of its absolute configuration. Our synthesis featured an extensive use of cobalt-catalyzed Mukaiyama-type cyclization of γ-hydroxy olefins for stereoselective formation of all the tetrahydrofuran rings found in the natural product, and a late-stage Stille-type coupling for convergent assembly of the entire carbon backbone. Four candidate diastereomers of amphirionin-2 were synthesized in a unified, convergent manner, and their spectroscopic/chromatographic properties were compared with those of the authentic material. The present study culminated in the reassignment of the C5/C7 relative configuration, assignment of the C12/C18 relative configuration, and determination of the absolute configuration of amphirionin-2.

An extensive application of cobalt-catalyzed Mukaiyama-type cyclization of γ-hydroxy olefins and a late-stage Stille-type reaction enabled syntheses of four diastereomers of amphirionin-2 to establish its absolute configuration.     

Development of a monolithic silica extraction tip for the analysis of proteins

In proteomics, pre-treatment of sample is the most important procedure to remove the matrix for interfacing with mass spectrometry (MS). Additionally, for the samples with low concentration, the process of pre-concentration is required before MS analysis. We have newly developed solid-phase extraction (SPE) tool with pipette-tip shape for purification of bio-samples of various characteristics, utilizing monolithic silica gel as medium. The monolithic silica surface was modified with a C18 phase or coated with titania phase. A C18-bonded tip and a non-modified tip were used for sample concentration, desaltination and removal of detergents from sample. A titania-coated tip was also applied for purification and concentration of phosphorylated peptides. This novel pre-treatment method using monolithic silica extraction tip is much effective and suitable for protein analysis.     

Asymmetric Total Synthesis of Cytotrienin A: Late-Stage Installation of C11 Side Chain onto the Macrolactam Scaffold

Cytotrienin A, an ansamycin-class antibiotic, exhibits potent apoptosis-inducing activity and has attracted much attention as a lead compound for anticancer drugs. Herein, we report a new asymmetric synthetic route to cytotrienin A, employing an unexplored approach involving the late-stage installation of a C11 side chain onto the macrolactam core. In this strategy, we utilized the redox properties of hydroquinone and installed a side chain on the sterically hindered C11 hydroxy group by the traceless Staudinger reaction. This study also demonstrated that the boron-Wittig/iterative Suzuki–Miyaura cross-coupling sequence was effective for the concise and selective construction of the (E,E,E)-conjugated triene moiety. The developed route opens new opportunities for the structure–activity relationship studies of the side chains of these ansamycin antibiotics and the preparation of other synthetic analogs and chemical probes for further biological studies.     

Identification and Quantification of Aconitines and Colchicine in Serum,Urine, and Plants using MonoSpin C18 and LC-MSMS

Chromatographia - Aconitum and Colchicum are known to be highly toxic plants based on their respective toxins, namely aconite and colchicine. Aconite and colchicine poisoning generally occurs...     

Effect of Rehabilitation Nutrition Care Process on Physical Function in Lung Cancer Cachexia: A Case Report

Objectives: Patients with cancer cachexia have poor adherence to treatment, which affects their prognosis. Currently, there are many studies on the effects of rehabilitation on cancer cachexia, but there is a lack of evidence on the effects of nutrition therapy alone or in combination with rehabilitation and nutrition therapy. This article describes a case in which rehabilitation nutrition care process was effective in a patient with lung cancer who developed cancer cachexia. Methods: A 68-year-old woman was hospitalized for treatment of lung adenocarcinoma. The patient had moderate malnutrition, sarcopenia, and cachexia at the time of admission, so the authors intervened according to rehabilitation nutrition care process. The physiotherapist mainly prescribed resistance training and aerobic exercise, 40-60 minutes a day, 5-6 days a week. And the dietitian provided oral nutritional supplements (100 kcal, branched-chain amino acid: 3.0 g) in addition to hospital food and adjusted the patient''s energy intake to 26.96-33.05 kcal/kg/day and protein intake to 1.07-1.14 g/kg/day. Outcomes: Comparing the initial evaluation with the discharge, nutritional status, such as body mass index and skeletal muscle mass, and physical functions, such as maximum grip strength, gait speed, and functional independence measure (motor items), were improved. Conclusions: Rehabilitation nutrition care process-based interventions may improve nutritional status and physical functions more than exercise therapy alone in patients with lung cancer cachexia.     

Complementary Role of GlcNAc6ST2 and GlcNAc6ST3 in Synthesis of CL40-Reactive Sialylated and Sulfated Glycans in the Mouse Pleural Mesothelium

Sialyl 6-sulfo Lewis X (6-sulfo sLe^X) and its derivative sialyl 6-sulfo N-acetyllactosamine (LacNAc) are sialylated and sulfated glycans of sialomucins found in the high endothelial venules (HEVs) of secondary lymphoid organs. A component of 6-sulfo sLe^X present in the core 1-extended O-linked glycans detected by the MECA-79 antibody was previously shown to exist in the lymphoid aggregate vasculature and bronchial mucosa of allergic and asthmatic lungs. The components of 6-sulfo sLe^X in pulmonary tissues under physiological conditions remain to be analyzed. The CL40 antibody recognizes 6-sulfo sLe^X and sialyl 6-sulfo LacNAc in O-linked and N-linked glycans, with absolute requirements for both GlcNAc-6-sulfation and sialylation. Immunostaining of normal mouse lungs with CL40 was performed and analyzed. The contribution of GlcNAc-6-O-sulfotransferases (GlcNAc6STs) to the synthesis of the CL40 epitope in the lungs was also elucidated. Here, we show that the expression of the CL40 epitope was specifically detected in the mesothelin-positive mesothelium of the pulmonary pleura. Moreover, GlcNAc6ST2 (encoded by Chst4) and GlcNAc6ST3 (encoded by Chst5), but not GlcNAc6ST1 (encoded by Chst2) or GlcNAc6ST4 (encoded by Chst7), are required for the synthesis of CL40-positive glycans in the lung mesothelium. Furthermore, neither GlcNAc6ST2 nor GlcNAc6ST3 is sufficient for in vivo expression of the CL40 epitope in the lung mesothelium, as demonstrated by GlcNAc6ST1/3/4 triple-knock-out and GlcNAc6ST1/2/4 triple-knock-out mice. These results indicate that CL40-positive sialylated and sulfated glycans are abundant in the pleural mesothelium and are synthesized complementarily by GlcNAc6ST2 and GlcNAc6ST3, under physiological conditions in mice.     

Lithium ion phase-transfer reaction at the interface between the lithium manganese oxide electrode and the nonaqueous electrolyte

The lithium ion phase-transfer reaction between the spinel lithium manganese oxide electrode and a nonaqueous electrolyte was investigated by the ac impedance spectroscopic method. The dependence of the impedance spectra on the electrochemical potential of the lithium ion in the electrode, the lithium salt concentration in the electrolyte, the kind of solvent, and the measured temperature were examined. Nyquist plots, obtained from the impedance measurements, consist of two semicircles for high and medium frequency and warburg impedance for low frequency, indicating that the reaction process of two main steps for high and medium frequency obey the Butler-Volmer type equation and could be related to the charge-transfer reaction process accompanied with lithium ion phase-transfer at the interface. The dependency on the solvent suggests that both steps in the lithium ion phase-transfer at the electrode/electrolyte interface include the desolvation process and have high activation barriers.     

Silica gel-promoted convenient synthesis of 2-bromo-3-hydroxybenzoate derivatives

A convenient silica gel-promoted synthesis of 2-bromo-3-hydroxybenzoate derivatives has been developed via the Diels–Alder reaction of furans with methyl 3-bromopropiolate, followed by a ring-opening aromatization. In addition, 2-bromo-3-methoxybenzoate, derived from 2-bromo-3-hydroxybenzoate with iodomethane, was found to be a good substrate for Pd-catalyzed cross-coupling reactions, despite its sterically hindered structure.