The stereocontrolled total synthesis of (-)-ephedradine A has been accomplished. The synthesis features an asymmetric C-H insertion reaction, an intramolecular ester-amide exchange reaction, and a Sharpless asymmetric aminohydroxylation reaction. Construction of the complex macrocyclic ring was performed by Ns-strategy and an intramolecular aza-Wittig reaction.

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Boron neutron capture therapy (BNCT) is a unique anticancer technology that has demonstrated its efficacy in numerous phase I/II clinical trials with boronophenylalanine (BPA) and sodium borocaptate (BSH) used as 10B delivery agents. However, continuous drug administration at high concentrations is needed to maintain sufficient 10B concentration within tumors. To address the issue of 10B accumulation and retention in tumor tissue, we developed MMT1242, a novel boron-containing α-d-mannopyranoside. We evaluated the uptake, intracellular distribution, and retention of MMT1242 in cultured cells and analyzed biodistribution, tumor-to-normal tissue ratio and toxicity in vivo. Fluorescence imaging using nitrobenzoxadiazole (NBD)-labeled MMT1242 and inductively coupled mass spectrometry (ICP-MS) were performed. The effectiveness of BNCT using MMT1242 was assessed in animal irradiation studies at the Kyoto University Research Reactor. MMT1242 showed a high uptake and broad intracellular distribution in vitro, longer tumor retention compared to BSH and BPA, and adequate tumor-to-normal tissue accumulation ratio and low toxicity in vivo. A neutron irradiation study with MMT1242 in a subcutaneous murine tumor model revealed a significant tumor inhibiting effect if injected 24 h before irradiation. We therefore report that 10B-MMT1242 is a candidate for further clinical BNCT studies.

The ammonium-directed olefinic oxidation of a range of cyclic allylic and homoallylic amines has been investigated. Functionalization of a range of allylic 3-(N,N-dibenzylamino)cycloalk-1-enes with m-CPBA in the presence of Cl(3)CCO(2)H gives exclusively the corresponding syn-epoxide for the 5-membered ring (>99:1 dr), the anti-epoxide for the 8-membered ring (>99:1 dr), and predominantly the anti-epoxide for the 7-membered ring (94:6 dr). Oxidation of the homoallylic amines 3-(N-benzylamino)methylcyclohex-1-ene and 3-(N,N-dibenzylamino)methylcyclohex-1-ene gave, in both cases, the corresponding N-protected 1,2-anti-2,3-syn-3-aminomethylcyclohexane-1,2-diol with high levels of diastereoselectivity (>or=90:10 dr). The versatile synthetic intermediates resulting from these oxidation reactions are readily transformed into a range of amino diols.