A Dual Role for the N-Perfluorobutanesulfinamide Auxiliary in an Asymmetric Decarboxylative Mannich Reaction.

Herein, we demonstrate that the enhanced electrophilicity of N-perfluorobutanesulfinamide auxiliary-derived imines enables a highly selective decarboxylative Mannich reaction under mild conditions. The molecular sieves-mediated transformation tolerates a broad substrate scope and produces chiral ß-amino thioesters in high yield. Additionally, we demonstrate that the N-perfluoroalkyl sulfinyl group can function as a phase tag for fluorous purification, thus enabling the rapid isolation of the chiral amine products by solid-phase extraction. The synthetic utility of this method is illustrated by the synthesis of sitagliptin, ruspolinone, and the natural product negamycin.

Dynamic changes of oligomeric amyloid ß levels in plasma induced by spiked synthetic Aß42.

BACKGROUND: A reliable blood-based assay is required to properly diagnose and monitor Alzheimer's disease (AD). Many attempts have been made to develop such a diagnostic tool by measuring amyloid-ß oligomers (AßOs) in the blood, but none have been successful in terms of method reliability. We present a multimer detection system (MDS), initially developed for the detection of prion oligomers in the blood, to detect AßOs. METHODS: To characterize Aß in the blood, plasma was spiked with synthetic amyloid-ß (Aß) and incubated over time. Then, the MDS was used to monitor the dynamic changes of AßO levels in the plasma. RESULTS: Increasing concentrations of AßOs were observed in the plasma of patients with AD but not in the plasma of normal control subjects. The plasma from patients with AD (n = 27) was differentiated from that of the age-matched normal control subjects (n = 144) with a sensitivity of 83.3% and a specificity of 90.0%. CONCLUSIONS: Synthetic Aß spiked into the blood plasma of patients with AD, but that of not elderly normal control subjects, induced dynamic changes in the formation of AßOs over time. AßOs were detected by the MDS, which is a useful blood-based assay with high sensitivity and specificity for AD diagnosis.

Generation of osteogenic construct using periosteal-derived osteoblasts and polydioxanone/pluronic F127 scaffold with periosteal-derived CD146 positive endothelial-like cells.

The purpose of this study was to generate tissue-engineered bone using human periosteal-derived osteoblasts (PO) and polydioxanone/pluronic F127 (PDO/pluronic F127) scaffold with preseeded human periosteal-derived CD146 positive endothelial-like cells (PE). PE were purified from the periosteal cell population by cell sorting. One of the important factors to consider in generating tissue-engineered bone using osteoprecursor and endothelial cells and a specific scaffold is whether the function of osteoprecursor and endothelial cells can be maintained in originally different culture medium conditions. After human PE were preseeded into PDO/pluronic F127 scaffold and cultured in endothelial cell basal medium-2 for 7 days, human PO were seeded into the PDO/pluronic F127 scaffold with PE, and then, this cell-scaffold construct was cultured in endothelial cell basal medium-2 with osteogenic induction factors, including ascorbic acid, dexamethasone, and ß-glycerophosphate, for a further 7 days. Then, this 2-week cultured construct was grafted into the mandibular defect of miniature pig. Twelve weeks after implantation, the animal was sacrificed. Clinical examination revealed that newly formed bone was seen more clearly in the defect with human PO and PDO/pluronic F127 scaffold with preseeded human PE. The experimental results suggest that tissue-engineered bone formation using human PO and PDO/pluronic F127 scaffold with preseeded human PE can be used to restore skeletal integrity to various bony defects when used in clinics.