(5R,8R,8aS)-(-)-5-(7-hept-3-enyl)-8-methylindolizidine | 109175-47-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚里西啶
• 英文名称: (5R,8R,8aS)-(-)-5-(7-hept-3-enyl)-8-methylindolizidine
• 英文别名: (-)-Indolizidine 235B；(5R,8R,8aS)-5-[(Z)-hept-4-enyl]-8-methyl-1,2,3,5,6,7,8,8a-octahydroindolizine
• CAS: 109175-47-5
• 化学式: C₁₆H₂₉N
• 分子量: 235.413
• InChiKey: XWQTZZRSURTNFY-BKBHSOPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (5R,8R,8aS)-(-)-5-(7-hept-3-enyl)-8-methylindolizidine 在 palladium on activated charcoal 氢气 作用下， 生成 [5R,8R,8aS]-(-)-5-heptyl-8-methyloctahydroindolizine
  参考文献：
  名称：

  Enantioselective Synthesis of Poison-Frog Alkaloid 237D and Determination of Absolute Stereochemistry

  摘要：

  An enantioselective synthesis of the 5-heptyl-8-methylindolizidine ((-)7) has been achieved. Alkaloid ((-)-7, (MW 237)) was used to determine the relative and absolute stereochemistry of the natural indolizidine 237D from frog skin as 5S, 8S, 9R using GC-IR and GC-MS. Chiral gas-chromatographic comparisons with catalytically reduced (+)-235B" and (-)-235B' indicated (-)-7 had the same absolute stereochemistry as the dihydro-product resulting from (-)-23513' and is naturally occurring in certain extracts of Panamanian poison frogs (Dendrobates).

  DOI：

  10.3987/com-04-10269
• 作为产物：
  描述：

  (5R,8R,8aS)-(-)-5-cyano-8-methylindolizidine 在 sodium tetrahydroborate 、 lithium diisopropyl amide 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 (5R,8R,8aS)-(-)-5-(7-hept-3-enyl)-8-methylindolizidine
  参考文献：
  名称：

  Enantioselective total syntheses of indolizidine alkaloids (-)-205A and (-)-235B

  摘要：

  Enantioselective total syntheses of indolizidine alkaloids (-)-205A and (-)-235B are described. The syntheses proceed via a common late-stage intermediate, alpha-aminonitrile 1. Absolute stereochemical control over the C8 and C8a stereocenters in these materials was achieved by a stereoselective crotylation reaction between chiral acyliminium ion (R)-3b and crotylmagnesium chloride. The selectivity of this reaction, which produced the (future)-8R,8aS configuration was complementary to the result obtained by crotylation of acyliminium ion (S)-3a with trans-crotyltrimethylsilane, which produced predominantly an adduct with the (future)-8S,8aS configuration. This latter crotyl lactam was converted to two additional diastereomers of alkaloid 205A. Comparison of the H-1 and C-13 NMR and optical rotation values of the four synthetic diastereomers of 205A with literature values supported the proposed assignment of the absolute and relative configuration of (-)-205A. The C-13 spectrum of synthetic (5R,8R,8aS)-235B was identical with that of natural 235B and supported the proposed assignment of relative configuration of the alkaloid. The optical rotation differed in sign and magnitude from the published value. Revised values of the optical rotations of (-)-205A and (-)-235B are suggested. This work constitutes the first enantioselective syntheses of 205A and 235B, which were prepared in 15 and 14 steps, respectively, from succinic anhydride, in an average overall yield of 17%.

  DOI：

  10.1021/jo00016a013

文献信息

• Enantiopure <i>N</i>-Acyldihydropyridones as Synthetic Intermediates:  Asymmetric Syntheses of Indolizidine Alkaloids (−)-205A, (−)-207A, and (−)-235B
  作者：Daniel L. Comins、Donald H. LaMunyon、Xinghai Chen

  DOI：10.1021/jo971448u

  日期：1997.11.1

  addition of 4-(benzyloxy)butylmagnesium bromide, and vinyl triflate formation provided 13 in a stereoselective fashion. Catalytic reduction of the vinyl triflate moiety, simultaneous cleavage of the benzyl ether and Cbz groups, and cyclization to give amino alcohol 14 was effected via a one-pot reaction. Oxidation of 14 with the Dess-Martin reagent gave a 97% yield of amino aldehyde 4. Synthesis of each

  吲哚并立定生物碱（-）-205A，（-）-207A和（-）-235B的简明不对称合成是在11个步骤中以高度立体控制完成的。将4-（1-丁烯基）溴化镁加到1-酰基吡啶鎓盐5中，该盐由4-甲氧基-3-（三异丙基甲硅烷基）吡啶和（+）-反式-2-（α-枯基）环己醇的氯甲酸酯原位制备产生91％的非对映异构纯二氢吡啶酮6。6的氧化裂解和随后的还原提供了81％产率的醇7。除去手性助剂和TIPS组（NaOMe; 10％HCl），用BnOCOCCl进行N-酰化，并用NCS / Ph（3）P处理，得到氯化物10。在C-3处甲基化，铜介导的共轭加成4- （苄氧基）丁基溴化镁和三氟甲磺酸乙烯酯的形成以立体选择性方式提供了13。三氟甲基乙烯基部分的催化还原，通过一锅法反应同时裂解苄基醚和Cbz基团，以及环化得到氨基醇14。用Dess-Martin试剂氧化14时，氨基醛4的产率为97％。三种标题生物碱中的每一种的合
• The total synthesis of (?)-indolizidines 205A and 235B
  作者：Yuji Shishido、Chihiro Kibayashi

  DOI：10.1039/c39910001237

  日期：——

  The total synthesis of (–)-indolizidines 205A and 235B, alkaloids from the arrow poison-frog, via a common chiral oxazino-lactam, prepared by an asymmetric intramolecular Diels–Alder reaction of an N-acylnitroso intermediate, is described.

  描述了通过普通的手性恶嗪基-内酰胺，由N-酰基亚硝基中间体的不对称分子内Diels-Alder反应制得的箭毒蛙的生物碱（-）-吲哚唑烷205A和235B的总合成。
• The enantioselective synthesis of poison-frog alkaloids (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″
  作者：Naoki Toyooka、Zhou Dejun、Hideo Nemoto、H. Martin Garraffo、Thomas F. Spande、John W. Daly

  DOI：10.1016/j.tetlet.2005.11.047

  日期：2006.1

  The enantioselective synthesis of indolizidines (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″ has been achieved and the absolute stereochemistry of both indolizidines 203A and 233D was established as 5S,8R,9S. The relative stereochemistry of natural 231C was established by the present asymmetric synthesis.

  indolizidines的对映选择性合成（ - ） - 203A，（ - ） - 209B，（ - ） - 231C，（ - ） - 233D，和（ - ） - 235B “已经达到，这两种indolizidines的绝对立体化学203A和233D为确立为5小号，8 - [R 9小号。天然231C的相对立体化学是通过本发明的不对称合成建立的。
• Enantiogenic total syntheses of (-)-indolizidines (bicyclic gephyrotoxins) 205A, 207A, 209B, and 235B via the intramolecular Diels-Alder reaction of a chiral N-acylnitroso compound
  作者：Yuji Shishido、Chihiro Kibayashi

  DOI：10.1021/jo00036a024

  日期：1992.5

  A general protocol for the enantiogenic total syntheses of a series of the 5-substituted 8-methylindolizidine class of alkaloids from the arrow poison frog, i.e., (-)-indolizidines 205A (1), 207A (2), 209B (3), and 235B (4), is described, in which a key step is the asymmetric intramolecular Diels-Alder reaction of the chiral N-acylnitroso compound 8 leading to the bicyclic oxazinolactam 7 which was utilized as a versatile common chiral intermediate for the preparation of these alkaloids. Subsequent introduction of the C-5 (in future) side chain was elaborated by means of a completely stereocontrolled process involving a Grignard reaction followed by reduction with NaBH4 in acidic media. The bicyclic oxazines 20a, 24, and 26 thus obtained were then subjected to reductive N-O bond cleavage followed by cyclodehydration using PPh3/CBr4/Et3N, which provided the (-)-enantiomers of the title alkaloids.
• A chiral synthesis of (8R,8aS)-hexahydro-8-methyl-5(1H)-indolizinone
  作者：Akiharu Satake、Isao Shimizu

  DOI：10.1016/s0957-4166(00)80326-2

  日期：1993.7

  The enantioselective synthesis of (8R,8aS)-hexahydro-8-methyl-5(1H)-indolizinone ((-)-13), which is a synthetic intermediate of 5,8-disubstituted indolizidine alkaloids has been carried out. Reaction of ethyl (E)-(4R, 5R)-8-benzyloxy-4, 5-epoxy-4-methyl-2-octenoate (4) with formic acid in the presence of Pd2(dba)3CHCl3 and n-Bu3P as a catalyst gave ethyl (E)-(4R, 5R)-8-benzyloxy-5-hydroxy-4-methyl-2-octenoate (5), which was converted to (-)-13 in 8 steps.