Synthesis of structurally unique natural products having glutamate receptor agonist and antagonist activities

为了研究谷氨酸受体与脑部疾病之间的关系，与谷氨酸受体相互作用的化合物的需求量很大。这些化合物也有助于设计一种新型的谷氨酸受体拮抗剂，可能具有作为神经保护剂的治疗价值。在这项研究中，我们以从草本植物中分离得到的谷氨酸受体激动剂Dysiherbaine和从Eupenicillium shearii PF1191菌株中分离得到的谷氨酸受体拮抗剂Kaitocephalin为研究对象，旨在探索合成这些化合物的有效方法。对于dysiherbaine，我们基于高度立体选择性的Hosomi-Sakurai反应，将侧链连接到吡喃环上，并通过钯催化的官能化三氟酚与L衍生的有机锌试剂的交叉偶联反应，合成了以D-葡萄糖为起始原料的关键中间体。当加纳醛与由1，3-丁二烯-2-基三丁基锡烷和SnCl4就地合成的2，3-丁二烯基三氯锡烷反应时，加成反应具有很好的反选择性，可转化为脑素。

The compounds that interact with glutamate receptors are in high demand in order to investigate the relationship between glutamate receptors and brain diseases. These compounds are also useful for designing a new type of glutamate receptor antagonist which may have therapeutic value as a neuroprotective agent. In this research, we focused on dysiherbaine, a glutamate receptor agonist isolated from Dysidea herbacea, and kaitocephalin, a glutamate receptor antagonist isolated from Eupenicillium shearii PF1191 strain, and aimed to develop efficient methods for the syntheses of these compounds.For dysiherbaine, we have developed an efficient method for the preparation of the key intermediate starting with D-glucose based on highly stereoselective Hosomi-Sakurai reaction to attach the side chain to the pyrane ring and palladium catalyzed cross-coupling reaction of the functionalized enol triflate and the organozinc reagent derived from L-iodoalanine to install the glutamic acid moiety.For kaitocephalin, we examined 1, 3-butadienylation of the Garner aldehyde derived from L-serine. When the Garner aldehyde was reacted with 2, 3-butadienyltrichlorostannane, prepared in site from 1, 3-butadien-2-yltributylstananne and SnCl_4, the addition reaction proceeded with perfect anti-selectivity to give the compound convertible to kaitocephalin.