(+/-)-Methyl Homosecodaphniphyllate | 118099-25-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: (+/-)-Methyl Homosecodaphniphyllate
• CAS: 118099-25-5
• 化学式: C₂₃H₃₇NO₂
• 分子量: 359.552
• InChiKey: MGLLZMAVACXEQY-ZSSXQRKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.55
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  38.33
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (+/-)-Methyl Homosecodaphniphyllate 在 lead(IV) acetate 作用下， 以 苯 为溶剂， 反应 0.75h， 以81%的产率得到(+/-)-1,2-Didehydro-2,15-cyclo-1,12-secodaphnan-23-oic acid methyl ester
  参考文献：
  名称：

  Daphniphyllum Alkaloids. 17. A Possibly Biomimetic Transformation of the Secodaphnane to the Daphnane Skeleton

  摘要：

  An investigation of conversion of the secodaphnane to the daphnane skeleton has been carried out. Treatment of oxaziridine 16 with various Lewis acids resulted in rearrangements involving migration of the C15-C16 bond. However, oxazolidine 28, in which the N-O bond is constrained to be roughly antiperiplanar to the C12-C16 bond, ionizes with predominant cleavage of this C-C bond when treated with a variety of trialkylaluminum reagents. The preferred reagent for simple cleavage of the C12-C16 bond is trimethylaluminum, which converts 28 into unsaturated imines 30-32 in approximately 90% yield. The major isomer of this fragmentation process, compound 30, was converted by the process summarized in Scheme 10 into (+/-)-daphnan-23-ol (43), which has previously been converted into (+/-)-methyl homodaphniphyllate (44). Remarkably, conditions were also found that convert 28 directly into the daphnane skeleton. For example, 28 reacts with diisobutylaluminum hydride in toluene to give daphnanes 34 and 35 in approximately 80% yield.

  DOI：

  10.1021/jo00110a014
• 作为产物：
  描述：

  (E)-9-iodo-2,6-dimethylnona-2,6-diene 在 chromium(VI) oxide 、 Wilkinson's catalyst 氢氧化钾 、 草酰氯 、 硫酸 、 ammonium acetate 、 氨 、 水 、 氢气 、 四丁基硫酸氢铵 、 二异丁基氢化铝 、 对甲苯磺酸 、 臭氧 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 二氯甲烷 、 丙酮 、 甲苯 、 苯 为溶剂， 反应 84.67h， 生成 (+/-)-Methyl Homosecodaphniphyllate
  参考文献：
  名称：

  Daphniphyllum alkaloids. 12. A proposed biosynthesis of the pentacylic skeleton. proto-Daphniphylline

  摘要：

  A biosynthetic proposal for the pentacyclic skeleton of the Daphniphyllum alkaloids is put forth (Scheme I) and various ramifications are examined experimentally. proto-Daphniphylline (11), the putative product of this hypothetical biogenesis, has been prepared by a convergent synthesis that starts with amide 14, alpha,beta-unsaturated ester 15, and homogeranyl iodide (Scheme II) and employs a highly efficient tetracyclization process previously used for the synthesis of (+/-)-methyl homosecodaphniphyllate (30) (Scheme III). The structure of proto-daphniphylline was confirmed by converting it into 30. The mechanism of the first stage of the tetracyclization process was investigated with the bis-homoneryl analogues 36/37. Treatment of these aldehydes successively with ammonia and acetic acid provided tetracyclic imine 38, suggesting that the cyclization reaction is a concerted Diels-Alder reaction rather than a stepwise process. Dialdehydes 27/28 were converted into 1,2-dihydro-proto-daphniphylline (29) by a version of the tetracyclization process wherein methylamine (or glycine) is substituted for ammonia. proto-Daphniphylline has also been prepared in a one-pot, two-stage process from the acyclic dialdehydes 51 and 55. Several versions of this pentacyclization process have been worked out. In the simplest, 51 or 55 is treated successively with ammonia and hot acetic acid to afford 11 in 15 +/- 2% yield. A slightly more elaborate protocol, a three-stage process that utilizes NaOH in benzene, ammonia in DMSO, and hot acetic acid, provided 11 in 49.4% overall yield. However, the most efficient pentacyclization process discovered employs successive reactions with methylamine (or glycine) and hot acetic acid. Under these conditions, 17,18-dihydro-proto-daphniphylline (29) is produced in 65% yield. The latter process is one of the most efficient reaction cascades ever discovered; it results in the formation of five rings, four carbon-carbon bonds, two carbon-nitrogen bonds, and concludes with the selective saturation of one of the three double bonds in proto-daphniphylline!

  DOI：

  10.1021/jo00035a009

文献信息

• Daphniphyllum alkaloids. 11. Biomimetic total synthesis of methyl homosecodaphniphyllate. Development of the tetracyclization reaction
  作者：Clayton H. Heathcock、Marvin M. Hansen、Roger B. Ruggeri、John C. Kath

  DOI：10.1021/jo00035a008

  日期：1992.4

  A biomimetic total synthesis of (+/-)-methyl homosecodaphniphyllate has been developed. The synthesis starts with a triply convergent, tandem Michael addition-enolate alkylation, wherein amide 9, enoate 7, and alkyl iodide 5 are assembled in essentially quantitative yield to obtain compounds 13, 14, and 15. The major isomer 13 is converted in three steps into a 1:1 mixture of diols 18a and 18b. These diols are subjected to a two-step process involving Swern oxidation and treatment of the resulting dialdehyde sequentially with ammonia and acetic acid; pentacyclic unsaturated amine 23 is obtained in 82% yield. Three additional functional group steps are used to convert 23 into racemic methyl homosecodaphniphyllate ((+/-)-4). The synthesis requires nine steps and proceeds in 48% overall yield from 5, 7, and 9. The tetracyclization process was shown to proceed via dialdehyde 26, tricyclic aza diene 27, and tetracyclic imine 28. An interesting and potentially useful variant of the tetracyclization procedure employs methylamine or benzylamine instead of ammonia. In this modification, the final reaction product is pentacyclic amine 29, in which the isopropenyl double bond has also been reduced. It is suggested that this reduction occurs by intramolecular hydride transfer at the stage of cationic intermediate 33.