Welwitindolinone C synthetic studies. Construction of the welwitindolinone carbon skeleton via a transannular nitrone cycloaddition

Described is the construction of the N-methylwelwitindolinone C core via an efficient strategy that employs a sequential rhodium carbenoid-mediated O–H insertion, Claisen rearrangement and transannular [3+2] nitrone cycloaddition

Boron delivery for boron neutron capture therapy targeting a cancer-upregulated oligopeptide transporter

Boron neutron capture therapy (BNCT) is a radiotherapy utilizing the neutron capture and nuclear fission reaction of 10B taken up into tumor cells. The most commonly used boron agent in BNCT, p-borono-l-phenylalanine (BPA), is accumulated in tumors by amino acid transporters upregulated in tumor cells. Here, by using dipeptides of BPA and tyrosine (BPA-Tyr and Tyr-BPA), we propose a novel strategy of selective boron delivery into tumor cells via oligopeptide transporter PEPT1 upregulated in various cancers. Kinetic analyses indicated that BPA-Tyr and Tyr-BPA are transported by oligopeptide transporters, PEPT1 and PEPT2. The intrinsic oligopeptide transport activity in tumor cells clearly correlated with PEPT1 protein expression level but not with PEPT2, suggesting that PEPT1 is the predominant oligopeptide transporter at least in tumor cell lines. Furthermore, using BPA-Tyr and Tyr-BPA, boron was successfully delivered into PEPT1-expressing pancreatic cancer AsPC-1 cells via a PEPT1-mediated mechanism. Intravenous administration of BPA-Tyr into the mice bearing AsPC-1 xenograft tumors resulted in significant boron accumulation in the tumors. It is proposed that the oligopeptide transporters, especially PEPT1, are promising candidates for molecular targets of boron delivery in BNCT. The BPA-containing dipeptides would have a potential for the development of novel boron carriers targeting PEPT1. Keywords: Boron delivery, Boron neutron capture therapy, p-Borono-l-phenylalanine-containing dipeptide, Oligopeptide transporter, PEPT

Emphysematous pyelonephritis with massive renal parenchymal gas and fluid collection : A Case report

A 76-year-old female patient with diabetes was referred to our hospital for evaluation of a 1-week history of left abdominal pain with loss of appetite. Laboratory data showed markedly elevated neutrophils. Abdominal X-ray showed massive gas and fluid collection in the left pararenal space, resembling an intestinal obstruction. Abdominal computed tomography revealed renal parenchymal gas and fluid and led to the correct diagnosis of emphysematous pyelonephritis. Based on these findings, this patient was immediately transferred to the intensive care unit. She underwent emergent ne-phrectomy and was discharged 28 days after surgery without complications.（Kitakanto Med J2013； 63：141～145