P-22 カイニン酸の全合成(ポスター発表の部)

• 家門 拓麻

  阪大院薬

• 入船 弥生

  阪大院薬

• 田中 徹明

  阪大院薬

• 好光 健彦

  阪大院薬

書誌事項

タイトル別名

• P-22 Total Synthesis of Kainic Acid(Poster Presentation)

抄録

Kainic acid (1) is a neuroexcitatory amino acid, isolated by Takemoto and co-workers in 1953 from the seaweed Digenea simplex.' Thereafter, a number of structurally related compounds have been identified, including domoic acid (2), acromelic acid (3), and isodomoic acid (4), all of which share a common trisubstituted proline motif. Their unique biological activities have inspired widespread interest in establishing chemical access to this class of natural amino acids. Herein, we report the total synthesis of (±)-kainic acid (1), in which a novel photochemical sp^3C-H carbamoylation of cis-fused azabicyclo[4.3.0]nonane 10 has been devised to construct the highly substituted amino acid motif. 1. Photochemical sp^3C-H Carbamovlation of Tertiary Amine Photolysis of tertiary amines in the presence of a photosensitizer serves as a powerful means for cleaving the nitrogen-substituted sp^3C-H bonds. Evaluation of the photolysis conditions led to the discovery that cyclic amine 10 (1.0 equiv) underwent sp^3C-H carbamoylation with phenyl isocyanate (1.5 equiv) in the presence of 4,4'-dimethoxybenzophenone (0.2 equiv) to afford anilide 9 along with biscarbamoylated compound 11. This is, as far as we know, the first successful example of the direct production of an amino acid anilide from a tertiary amine via intermolecular addition of photochemically generated a-amino alkyl radical to phenyl isocyanate.2. Total Synthesis of (+)-Kainic Acid With suitably functionalized anilide 9 available, further synthetic manipulations were made to yield kainic acid (1). By common deprotection-protection protocols, anilide 9 was successfully converted to tetracyclic motif 12. Acidic hydrolysis of 12 followed by regioselective silylation of the resultant diol afforded silyl ether 13 regioselectively. Dehydration of 13 with Martin sulfurane successfully afforded alkene 14, which, by acid treatment followed by Dess-Martin oxidation, provided enone 15 in high yield. Enone 15 was then transformed into α,β-unsaturated enone 16 through Me_2CuLi-mediated methylation followed by silylation with TMSC1 and Pd(OAc)_2-mediated oxidation of the resultant silyl enol ether. Convex face selective 1,4-silylation of enone 16 produced quaternized compound 17 as a single detectable isomer. We envisioned that the silylated ketone 17 would exhibit a high degree of regiocontrol in the Baeyer-Villiger oxidation due to the steric demand caused by the hindered substituent. To our delight, the oxidative ring expansion of compound 17 with mCPBA was found to yield desired seven-membered lactone 18a. Furthermore, this transformation led us to discover an unusual silyl-migration reaction that produced 18b. It is likely that the stabilization of the cationic 0-carbon through anchimeric assistance of the silyl group enables the unique migration. Then, compounds 18a and 18b were each subjected to the desilylative olefination with HF. Py to deliver olefin 19, respectively, as a single product. Hydrolysis of compound 19 with 3N NaOH took place smoothly to eventually furnish kainic acid (1) as the sole product. The spectroscopic and analytical data of the synthesized kainic acid (1) exactly matched those reported in the literature.

収録刊行物

• 天然有機化合物討論会講演要旨集

  天然有機化合物討論会講演要旨集 53 (0), 547-552, 2011

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390282681056745600
• NII論文ID: 110009986593
• DOI: 10.24496/tennenyuki.53.0_547
• ISSN: 24331856
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可