Asymmetric dearomatization/cyclization enables access to polycyclic chemotypes

Enantioenriched, polycyclic compounds were obtained from a simple acylphloroglucinol scaffold. Highly enantioselective dearomatization was accomplished using a Trost ligand-palladium(0) complex. A computational DFT model was developed to rationalize observed enantioselectivities and revealed a key reactant-ligand hydrogen bonding interaction. Dearomatized products were used in visible light-mediated photocycloadditions and oxidative free radical cyclizations to obtain novel polycyclic chemotypes including tricyclo[4.3.1.01,4]decan-10-ones, bicyclo[3.2.1]octan-8-ones and highly-substituted cycloheptanones.R24 GM111625 - NIGMS NIH HH

Primary Gastrointestinal Stromal Tumor of the Liver with Cystic Changes

Gastrointestinal stromal tumors (GISTs) are known to originate specifically from the intestinal cells of Cajal located in the gastrointestinal mesenchyme. GISTs developing outside of the digestive tract have barely been reported. We encountered a first case of large primary GISTs in the liver with cystic changes. A 63-year-old man with a past history of brain infarction visited our hospital. The computed tomography (CT) revealed a 6-cm and a 10-cm mass in the right and the caudal lobe of the liver, respectively. These tumors have marginal enhancement in the arterial phase; however, they presented as hypodense in the internal tumor sites. Both liver tumors had cystic changes. Gastrointestinal examinations using endoscopy revealed no other gastrointestinal tumors, and [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/CT revealed multiple bone metastases in addition to the liver tumors. The liver tumor specimens were composed of spindle cells, and the immunohistochemical staining for c-Kit and for DOG1, as discovered on GIST, was positive. The patient was diagnosed with primary hepatic GIST with cystic changes

Bioprospection of cellulolytic and lipolytic South Atlantic deep-sea bacteria

Background: Cellulases and lipases have broad industrial application, which calls for an urgent exploration of microorganisms from extreme environments as valuable source of commercial enzyme. In this context, the present work describes the bioprospection and identification of deep-sea bacteria that produce cellulases and lipases, as well their optimal temperature of activity. Results: The first step of this study was the screening of cellulolytic and lipolytic deep-sea bacteria from sediment and water column, which was conducted with substrates linked with 4-Methylumbelliferyl. Among the 161 strains evaluated, 40 were cellulolytic, 23 were lipolytic and 5 exhibited both activities. Cellulolytic and lipolytic bacteria are more common in sediment than at the water column. Based on the ability to produce cellulases and lipases three isolates were selected and identified (16S rRNA sequencing) as Bacillus stratosphericus , B. aerophilus and B. pumilus . Lipases of strain B. aerophilus LAMA 582 exhibited activity at a wide temperature range (4\uba to 37\ubaC) and include psychrophilic behaviour. Strain Bacillus stratosphericus LAMA 585 can growth in a rich (Luria Bertani) and minimal (Marine Minimal) medium, and does not need an inducer to produce its mesophilic cellulases and lipases. Conclusions: Deepsea sediments have great potential for bioprospection of cellulase and lipase-producing bacteria. The strains LAMA 582 and LAMA 585 with their special features, exhibit a great potential to application at many biotechnology process

Integration of neurogenesis and angiogenesis models for constructing a neurovascular tissue

Neurovascular unit (NVU) is a basic unit in the brain, including neurons, glial cells, blood vessels and extracellular matrix. This concept implies the importance of a three-dimensional (3D) culture model including these cell types for investigating brain functions. However, little is known about the construction of an in vitro 3D NVU model. In the present study, we aimed at constructing 3D neurovascular tissues by combining in vitro neurogenesis and angiogenesis models using a microfluidic platform, which is a critical step toward the NVU construction in vitro. Three gel conditions, which were fibrin gel, fibrin-Matrigel mixed gel and fibrin-hyaluronan mixed gel, were investigated to optimize the gel components in terms of neurogenesis and angiogenesis. First, fibrin-Matrigel mixed gel was found to promote neural stem cell (NSC) differentiation into neurons and neurite extension. In particular, 3D neural networks were constructed in 2–8 mg/ml fibrin-Matrigel mixed gel. Second, we found that capillary-like structures were also formed in the fibrin-Matrigel mixed gel by coculturing brain microvascular endothelial cells (BMECs) and human mesenchymal stem cells (MSCs). Finally, we combined both neural and vascular culture models and succeeded in constructing 3D neurovascular tissues with an optimized seeding condition of NSCs, BMECs and MSCs

Enantioselective Approach to Polycyclic Polyprenylated Acylphloroglucinols via Catalytic Asymmetric Intramolecular Cyclopropanation

The formal enantioselective total synthesis of nemorosone, garsubellin A, clusianone, and hyperforin is described. The catalytic asymmetric intramolecular cyclopropanation (CAIMCP) of an α-diazo ketone, a common synthetic intermediate for the above four polycyclic polyprenylated acylphloroglucinols previously reported by us, exhibited low enantioselectivity. However, CAIMCP of the corresponding α-diazo β-keto sulfone afforded the desired product in 79% yield with 84% ee. Investigation of the CAIMCP of the α-diazo β-keto sulfone demonstrated the formation of a rearrangement product in the presence of molecular sieves 4 Å, whereas, in the presence of H₂O, the byproduct derived from ring-opening of the desired cyclopropane was observed. X-ray crystallographic analysis suggested that the above two products are derived from the same chiral intermediate. The product derived from ring-opening of the cyclopropane was successfully transformed to the respective synthetic intermediates for the total syntheses of nemorosone, garsubellin A, clusianone, and hyperforin, which had previously been reported by us

Enantioselective Approach to Polycyclic Polyprenylated Acylphloroglucinols via Catalytic Asymmetric Intramolecular Cyclopropanation

The formal enantioselective total synthesis of nemorosone, garsubellin A, clusianone, and hyperforin is described. The catalytic asymmetric intramolecular cyclopropanation (CAIMCP) of an α-diazo ketone, a common synthetic intermediate for the above four polycyclic polyprenylated acylphloroglucinols previously reported by us, exhibited low enantioselectivity. However, CAIMCP of the corresponding α-diazo β-keto sulfone afforded the desired product in 79% yield with 84% ee. Investigation of the CAIMCP of the α-diazo β-keto sulfone demonstrated the formation of a rearrangement product in the presence of molecular sieves 4 Å, whereas, in the presence of H₂O, the byproduct derived from ring-opening of the desired cyclopropane was observed. X-ray crystallographic analysis suggested that the above two products are derived from the same chiral intermediate. The product derived from ring-opening of the cyclopropane was successfully transformed to the respective synthetic intermediates for the total syntheses of nemorosone, garsubellin A, clusianone, and hyperforin, which had previously been reported by us