Basic Studies and Synthetic Application of Enzyme Functions

酶如酯酶、脂肪酶和氧化酶促进生命系统中的基本和重要反应。在本研究中，我们开发了这些酶的合成应用.酶促酯交换法将meso-氮丙啶类化合物转化为光学活性的顺式-二取代氮丙啶类化合物，顺式-二取代氮丙啶类化合物是一类重要的化合物，因为它们是丝裂霉素C和FR-900482等抗肿瘤药物的组成部分，并且在抗肿瘤活性中起着关键作用。内消旋氮丙啶衍生物容易由市售的顺式-2-丁烯-1，4-二醇制备。在有机溶剂（二异丙醚）中，在酶的存在下，用亲核试剂（丁醇）进行内消旋衍生物转化为光学活性衍生物。在所筛选的多种脂肪酶和酯酶中，廉价易得的脂肪酶Amano P已被证明在催化酯交换反应中具有高度的对映选择性（95-98%ee）。具有光学活性的顺式二取代氮杂环丙烷有望成为合成特殊氨基酸的前体。通过氮杂环丙烷的分子内进攻羟基开环反应得到了苏型β-氨基醇。然后将氨基醇转化为不寻常的氨基酸，这些氨基酸是生物活性肽如bestatin和apthanin G的关键成分。过氧化物酶促进不饱和二元醇转化为环醚在乳过氧化物酶（LPO）和溴化钠存在下，多种不饱和二元醇转化为环醚。前体二醇的结构决定了环化的方式。因此，分别区域选择性地形成五元环醚和八元环醚。通过脂质过氧化反应，从（3 Z，6S，7S）-月桂二醇的前体转化为双环天然溴醚月桂精。

Enzymes such as esterase, lipase, and oxidase promote fundamental and important reactions in the living systems. In this research, we have developed the synthetic applications of these enzymes.1. Conversion of meso-aziridines into optically active cis-disubstituted aziridines by enzymatic transesterification.Cis-disubstituted aziridines are important class of compounds since they are the consituents of antitumor agents such as mytomycin C and FR-900482 and also they play a key role on the antitumor activity. Meso-aziridine derivatives are readily prepared from commercially available cis-2-butene-1,4-diol. Transformation of the meso-derivatives into the optically active ones was carried out with a nucleophile (butanol) in oraganic solvent (diisopropyl ether) in the presence of the enzyme. Among a variety of lipases and esterases screened, readily available and cheep lipase, Amano P, has proved to highly enantioselective in catalyzing the transesterification reactions (95-98%ee). Optically active cis-disubstituted aziridines are expected to be useful precursors of unusual amino acids. Threo-beta-amino alcohols were obtained by the ring-opening reaction of aziridines through intramolecular attack of a hydroxy group. The amino alcohols were then transformed to the unusual amino acids which are the key constituents of biologically active peptides such as bestatin and apthanin G.2. Peroxidase-promoted transformation of unsaturated diols into cyclic ethers.A variety of unsaturated diols were transformed into cyclic ethers in the presence of lactoperoxidase (LPO) and sodium bromide. Structures of the precursor diols determined the mode of cyclization. Thus, five-membered cyclic ethers and eight- membered cyclic ethers were regioselectively formed, respectively. A bicyclic natural bromo ether, laureatin, have been also transformed from the original precursor, (3Z,6S,7S)-laurediol by LPO.