Studies on the synthesis of physiologically active furanocembrane derivatives

生理活性呋喃西松衍生物的合成研究

• 批准号: 13672238
• 负责人: TSUBUKI Masayoshi
• 金额: $ 1.86万
• 依托单位: Hoshi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672238/
• 关键词: Cyclic furfuryl ether; Wittig rearrangement; Furanocembrane; Kallolide A; Bipinnatin J; Pinnatin A; Cyclopropanation; Cross-coupling; Stilleクロスカップリング; γ-ブテノリド; グリセルアルデヒド; ゲルソラン; フラノジテルペン; 鈴木クロスカップリング; Witting転位; シュードプテラン

A stereocontrolled synthesis of anti-and syn-β-isopropenyl alcohol moieties at the C(2)-C(3) positions of kallolide A and pinnatin A was accomplished employing the [2,3] Wittig rearrangement of (E)-and (Z)-cyclic furfuryl ethers. Both (5E)-and (5Z)-5,15-dimethyl-3,16-dioxabicyclo [11.2.1] hexadeca-1(15),5,13-trienes rearranged with high diastereoselectivity to give (2R^*,3R^*)-and (2R^*,3S^*)-3-isopropenyl-12-methyl-13-oxabicyclo[8.2.1]trideca-1(12), 10-dien-2-ols, respectively. Enantioselective Wittig rearrangement of (E)-and (Z)-furfuryl ethers using butyllithium and a chiral bis(oxazoline) was also examined to provide (2R, 3R)-homoallylic alcohol in up to 61% ee and (2R, 3S)-alcohol in up to 93% ee, respectively.A stereoselective synthesis of the cyclopropylfuran unit in pinnatin A was carried out. Cyclopropanation of vinylfuroate gave desired cycloporpylfuroate, albeit in low yield. Suzuki cross-coupling of cyclopropylboronic acid with bromofuroate afforded the corresponding (1R, 2R, 2'S)-5-[2-(1,4-dioxaspiro[4.5]decan-2'-yl)-2-methylcyclopropyl]-3-methyl-2-furoic acid methyl ester in 77% yield. This compound was converted into aldehyde, a key intermediate for the synthesis of pinnatin A. Chiral synthesis of the core structure of bipinnatin J was investigated. Stille cross-coupling of tributylstannylfuran with (Z)-bromoalkene gave (S, Z)-1-(5-tert-butyldimethylsiloxymethyl-4-methyl-2-furyl)-2-methyl-4,5-O-(p-methoxybenzylidene)-1-pentene stereoselectively. Ru-catalyzed cyclic carbonylation of allenyl alcohol afforded γ-lactone, (S, 1E, 5Z, 9E)-1-bromo-11-tert-butyldimethylsiloxy-4-hydroxy-2,10-dimethylundeca-1,5,9-triene-6-carboxylic acid lactone.

利用（E）-和（Z）-环状糠醚的[2，3] Wittig重排反应，立体控制地合成了kallocene A和pinnatin A的C（2）-C（3）位上的反式和顺式β-异丙烯醇部分。（5E）-和（5Z）-5，15-二甲基-3，16-二氧杂双环[11.2.1]十六碳-1（15），5，13-三烯以高非对映选择性重排，分别得到（2R ^*，3R ^*）-和（2R ^*，3S ^*）-3-异丙烯基-12-甲基-13-氧杂双环[8.2.1]十三碳-1（12），10-二烯-2-醇。利用丁基锂和手性双恶唑啉对（E）-和（Z）-糠基醚进行Wittig重排反应，得到了ee值分别为61%和93%的（2R，3R）-高烯丙醇和（2R，3S）-醇。糠酸乙烯酯的环丙烷化得到所需的糠酸环丙基酯，尽管产率低。环丙基硼酸与溴糠酸酯的Suzuki交叉偶联得到相应的（1R，2R，2 ′ S）-5-[2-（1，4-二氧杂螺[4.5]癸-2 ′-基）-2-甲基环丙基]-3-甲基-2-糠酸甲酯，产率77%。该化合物被转化为醛，醛是合成羽状花序素A的关键中间体。研究了bipinnatin J核心结构的手性合成。三丁基锡基呋喃与（Z）-溴代烯烃的Stille交叉偶联立体选择性地得到（S，Z）-1-（5-叔丁基二甲基甲硅烷基甲基-4-甲基-2-呋喃基）-2-甲基-4，5-O-（对甲氧基亚苄基）-1-戊烯。钌催化丙二烯醇环羰基化得到γ-内酯（S，1E，5Z，9E）-1-溴-11-叔丁基二甲基硅氧基-4-羟基-2，10-二甲基十一碳-1，5，9-三烯-6-羧酸内酯。

项目成果

H.F.Kasai, M.Tsubuki, et al.: "Separation of stereoisomers of several furan derivatives by capillary gas-----"Journal of Chromatography A. 977・1. 125-134 (2002)

H.F.Kasai、M.Tsubuki 等：“通过毛细管气体分离几种呋喃衍生物的立体异构体------”色谱杂志 A. 977・1 (2002)。

H.F.Kasai, M.Tsubuki et al.: "Separation of stereoisomers of several furan derivatives by capillary gas chromatography-mass spectrometry, supercritical fluid chromatography, and liquid chromatography using chiral stationary phases"Journal of Chromatograph

H.F.Kasai、M.Tsubuki 等人：“使用手性固定相通过毛细管气相色谱-质谱法、超临界流体色谱法和液相色谱法分离几种呋喃衍生物的立体异构体”Journal of Chromatograph

M.Tsubuki et al.: "Stereoselective Construction of a β-Isopropenyl Alcohol Moiety at the C(2) and (3) of Kallolide a and Pinnatin a Using a [2,3] Wittig Rearrangement of Cyclic Furfuryl Ethers"The Journal of Organic Chemistry. 68・26. 10183-10186 (2003)

M.Tsubuki 等人：“利用环状糠基醚的 [2,3] Wittig 重排，在 Kallolide a 和 Pinnatin a 的 C(2) 和 (3) 处立体选择性构建 β-异丙烯醇部分”The Journal of有机化学 68・26。

M.Tsubuki, et al.: "Stereoselective Construction of a β-Isopropenyl Alcohol Moiety at the C(2)---"The Journal of Organic Chemistry. 68・26. 10183-10186 (2003)

M.Tsubuki 等：“C(2) 处的 β-异丙烯醇部分的立体选择性构建---”有机化学杂志 68・26（2003 年）。

Masayoshi Tsubuki, Kazunori Takahashi, Toshio Honda: "Stereoselective Construction of a β-Isopropenyl Alcohol Moiety at the C(2) and (3) of Kallolide A and Pinnatin A Using a [2,3] Wittig Rearrangement of Cyclic Furfuryl Ethers"J.Org.Chem.. 68(26). 10183-

Masayoshi Tsubuki、Kazunori Takahashi、Toshio Honda：“利用环状糠基醚的 [2,3] Wittig 重排在 Kallolide A 和 Pinnatin A 的 C(2) 和 (3) 处立体选择性构建 β-异丙烯醇部分”J .有机化学.. 68(26)。