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

1)由于商品对氟苯丙氨酸价格昂贵，本论文以对氟氯苯丙氨酸和乙酰氨基丙二酸二乙酯为原料，采用常规方法合成了对氟苯丙氨酸。然而，这种分子中的F原子的含量不足以用磁共振成像(MRI)来测量。因此，以类似的方法新合成了五氟苯丙氨酸[Phe(F5)]，并将其用于制备几种含Phe(F5)的二肽。目前正在通过特定的寡肽转运体将这些多肽积累到金枪鱼细胞中。2)对硼苯丙氨酸(BPA)比苯丙氨酸(Phe(4F))更昂贵，而且富含^&lt；10&gt；B的化合物必须自行制备。为了避免使用诸如Snyder或Kirihata方法之类的有害策略，提出了一种以对溴苯甲醛为起始原料的新方法。在本研究过程中，我们首先计划制备N-氯乙酰-双酚A(CLAC-BPA)，用于酶促光学拆分。然而，由于CLAC-BPA的合成比较困难，所以我们改变了制备普通N-乙酰-BPA(Ac-BPA)的计划。作为本研究的结果，我们开发了一种有用的制备Ac-BPA的方法，采用温和的反应条件在苯环上进行对位硼化或在苯基上进行卤化反应。3)在本工作中，我们计划合成BPA与Phe(F_5)之间的嵌合化合物，即4-硼-2，3，5，6-四氟苯丙氨酸[BPA(F_4)]，目前正在进行该氨基酸的合成。双酚A(F4)的羧基还原得到的双酚A(F4)-醇似乎是促进硼中子俘获治疗(BNCT)的一个很好的候选者，即我们可以用MRI来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.