Novel Tandem Desulfurization and Hydroxylation in Aqueous Media (Towards the Asymmetric Synthesis of New and Effective Anti-cancer Agents)

水介质中的新型串联脱硫和羟基化（致力于新型有效抗癌剂的不对称合成）

基本信息

批准号：
15550031
负责人：
YODA Hidemi
金额：
$ 2.43万
依托单位：
Shizuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Recent disclosures from this laboratory have demonstrated SmI_2-promoted tandem desulfurization and high erythro-selective coupling reactions of aromatic lactams with carbonyl compounds. Although significant progress, thus, has been made in advancing the versatility of sulfur-substituted lactams, the lack of studies concerning the reactivity toward simple Lewis acids is surprising except the lactol type of compounds. Herein we wish to report our successful efforts for the development of novel Lewis acid-mediated tandem reaction of phenylthio-substituted alicyclic and aromatic lactams in aqueous media, leading to the γ-hydroxylated products, whose process was further applied to the convenient total synthesis of isoindolobenzazepine natural product, chilenine.Whereas the reactions with FeCl_3 and CuI gave the desired γ-hydroxylated product, but in low yield, respectively, use of CuCl or CuBr had a dramatic effect on the rate and smoothly brought about the taget compound in almost quantitative yields under these mild and readily available conditions. We were delighted to find that the same beneficial results were again obtained in reaction employing quaternary substituted phenylthiolactams containing aliphatic and aromatic alkyl side chains by replacement of the solvent system. We further found that the use of β-substituted and α,β-disubstituted γ-phenylthiolactams as well as the aromatic one underwent convenient reactions to afford the corresponding desulfurized hydroxylactams in quite high yields. In light of the above outcome, we turned our attention to the development of novel and convenient synthetic method of isoindolobenzazepine alkaloid, chilenine and accomplished the total synthesis of natural chilenine. This process will be widely applicable to the synthesis of other fused alkaloidal natural products such as new antitumor antibiotics, UCS 1025 series containing a quaternary hydroxyl group α to the nitrogen.

该实验室的最新披露表明，芳香族乳糖与羰基化合物的SMI_2促进串联脱硫化和高红细胞选择性偶联反应。尽管在推进硫取代的乳糖的多功能性方面取得了重大进展，但缺乏关于对简单刘易斯酸的反应性的研究令人惊讶，除了乳糖型的化合物类型。 Herein we wish to report our successful efforts for the Development of novel Lewis acid-mediated tandem reaction of phenylthio-substituted alicyclic and aromatic lactams in aqueous media, leading to the γ-hydroxylated products, whose process was further applied to the convenient total synthesis of isoindolobenzazepine natural product, chilenine.Whereas the reactions with FeCl_3 and CuI gave the所需的γ-羟基化产物，但分别以低产量的使用，使用CUCL或CUBR对速率产生了巨大的影响，在这些温和且易于使用的条件下，几乎定量的产率以几乎定量的产量使Tagget化合物顺利带来。我们很高兴发现，通过替换溶液系统，采用了含有脂肪族和芳香族烷基侧链的第四纪取代苯噻吩家苯乙烷的反应，再次获得了相同的有益结果。我们进一步发现，使用β-取代和α，α，β-取代的γ-苯基硫醇酰胺以及芳族人进行了方便的反应，以提供相应的脱硫化羟基酰胺，产量很高。鉴于上述结果，我们将注意力转向了新型和方便的综合方法的异丁替苯甲酰氮生物碱，甲状腺素，并实现了天然辣椒氨酸的总合成。该过程将广泛适用于其他融合的生物碱天然产物（例如新抗肿瘤抗生素）的合成，UCS 1025系列，其中包含二羟基α与氮的二级抗生素。