Toward the novel development for the diagnosis and treatment of cancer by the use of peptides that are accumulated into tumor cells.

1)由于商品4-氟苯丙氨酸[Phe(4F)]价格昂贵，我们以4-氟氯苄和乙酰氨基丙酸二乙酯为原料，采用常规方法合成了该氨基酸。然而，该分子中F原子的含量不足以用磁共振成像（MRI）测量。因此，以类似的方法合成了五氟苯丙氨酸[Phe(F_5)]，并制备了几种含Phe（F_5）的二肽。目前正在通过特定的寡肽转运体将这些肽积累到肿瘤细胞中。2)对硼苯丙氨酸（Bpa）比苯丙氨酸（4F）贵，富集^<10 b> B的化合物必须自行制备。为了避免施耐德或基里哈塔方法等有害策略的应用，阐明了一种使用对溴苯甲醛作为起始材料的新方法。在本研究过程中，我们首先计划制备n -氯乙酰双酚a （ClAc-Bpa）用于酶解光学分辨率。但是ClAc-Bpa的合成难度较大，因此我们将计划改为制备普通n -乙酰基双酚a （Ac-Bpa）。通过本研究，我们开发了一种利用苯环对位硼化或苯基位卤化的温和反应条件制备交联双酚a的方法。目前正在进行这种衍生物的酶光学分解。3)在这项工作中，我们新计划合成一种介于Bpa和Phe（F_4）之间的化合物，即4-硼-2,3,5,6-四氟苯丙氨酸[Bpa(F_4)]，目前我们正在进行该氨基酸的合成。通过还原Bpa（F_4）的羧基得到的Bpa(F_4)-ol似乎是促进硼中子捕获治疗（BNCT）的一个很好的候选物，即我们可以通过MRI检查癌细胞的确切位置，从而可以准确地用中子照射癌细胞。

1) Since commercial 4-fluorophenylalanine [Phe(4F)] is quite expensive, we synthesized this amino acid by conventional method from 4-fluorobenzyl chloride and diethyl acetamidomalonate. However, the content of F atom in this molecule is not enough for measurement by magnetic resonance imaging (MRI). Therefore, pentafluorophenylalanine [Phe(F_5)] was newly synthesized in a similar manner, and subjected to prepare several Phe(F_5)-containing dipeptides. Accumulation of these peptides into tunor cells via specific oligopeptide transporter is being currently undertaken.2) p-Boronophenylalanine (Bpa) is rather expensive than Phe(4F), and the compound enriched with ^<10>B must be prepared by ourselves. To avoid the application of a harmful strategy such as the Snyder or Kirihata method, a novel methodology using p-bromobenzaldehyde as a starting material was elucidated. In the course of this study, we first planned to prepare N-chloroacetyl-Bpa (ClAc-Bpa) for enzymatic optical resolution. However, the synthesis of ClAc-Bpa was quite difficult, and we thus changed the plan toward to prepare common N-acetyl-Bpa (Ac-Bpa). As a result of the present study, we developed a useful method to prepare Ac-Bpa by employing the mild reaction conditions for boronation at para-position on the phenyl ring or halogenation at benzyl-position. Enzymatic optical resolution of this derivative is being currently undertaken.3) During the course of this work, we newly planned to synthesize a chimeral compound between Bpa and Phe(F_5), i.e., 4-borono-2,3,5,6-tetrafluorophenylalanine [Bpa(F_4)], and we are currently undertaking the synthesis of this amino acid. Bpa(F_4)-ol that is obtainable by reduction of the carboxyl group of Bpa(F_4) seems to be a good candidate to promote boron neutron capture therapy (BNCT), i.e., we can check the exact location of cancer cells by MRI, and thus cancer cells can be irradiated accurately by neutron.