羟毒芹碱 | 495-20-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 羟毒芹碱
• 中文别名: 毒芹羟碱；假羥毒芹鹼；Ψ-羥毒芹鹼；羥毒芹鹼；?毒芹?
• 英文名称: (+)-conhydrine
• 英文别名: (1'R,2S)-2-[1'-(hydroxy)propyl]pireridine；(2'S,1R)-1-(2-piperidyl)propan-1-ol；1-piperidin-2-ylpropan-1-ol；(+)-α-conhydrine；conhydrine；α-conhydrine；(1R)-1-[(2S)-piperidin-2-yl]propan-1-ol
• CAS: 495-20-5
• 化学式: C₈H₁₇NO
• 分子量: 143.229
• InChiKey: VCCAAURNBULZRR-JGVFFNPUSA-N

物化性质

• 熔点：
  121°
• 比旋光度：
  D +10°
• 沸点：
  bp 226°
• 密度：
  0.9636 (rough estimate)
• 溶解度：
  Water (difficult), ethanol (easy), ether (easy)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  羟毒芹碱 在 磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  钌催化的不对称加氢高对映选择性合成手性环状氨基醇和对苯二甲酸

  摘要：

  一个高效对映和非对映选择性合成的手性顺式-β- ñ -烷基/芳基氨基环醇已经由外消旋的不对称氢化实现α氨基经由DKR环酮催化通过将[RuCl 2（（小号）-Xyl-SDP） （（R，R）-DPEN）]。该反应的对映选择性分别达到99.9％ee的用99：1分的顺式-选择性。还开发了一种实用的催化方法，可合成水合所有四个异构体。

  DOI：

  10.1021/ol901605a
• 作为产物：
  描述：

  1-Boc-哌啶 在 四甲基乙二胺 、 仲丁基锂 作用下， 反应 0.33h， 生成 羟毒芹碱
  参考文献：
  名称：

  .alpha.-Lithioamine synthetic equivalents: syntheses of diastereoisomers from Boc derivatives of cyclic amines

  摘要：

  Sequences of alpha'-lithiations and electrophilic substitutions of Boc-pyrrolidines, Boc-piperidines, and Boc-hexahydroazepines that provide compounds which are substituted adjacent to nitrogen are reported, and the pathways of the reactions are discussed. By this methodology monosubstituted 2 and disubstituted 2,4,2,6, and 2,5 Boc-piperidines are obtained as single or separable diastereoisomers consistent with equatorial lithiations and retentive electrophilic substitution in chair conformations. Both cis and trans 2,6-disubstituted diastereoisomers can be prepared, and control of diastereoselectivity is demonstrated by syntheses of solenopsin A, a 2,6-trans-disubstituted piperidine, and of Boc-dihydropinidine, a 2,6-cis-disubstituted piperidine. In the case of 3-methoxy-Boc-piperidine elimination of methoxide occurs upon lithiation, and with cis-2,4-disubstituted Boc-piperidines the electrophile is introduced with trans stereochemistry at C-6. These reactions are suggested to involve twist boat conformations consistent with an X-ray crystal structure of 2-methyl-6-(trimethylstannyl)-4-phenyl-N-Boc-piperidine. Boc-pyrrolidine lithiates more rapidly than Boc-piperidine, provides 2-substituted products with electrophiles, and on further lithiation-substitution gives 2,5-cis- and -trans-substituted products. Boc-perhydroazepine provides 2-substituted products by the sequence and on further lithiation-substitution gives 2,7-trans-disubstituted products.

  DOI：

  10.1021/jo00057a024

文献信息

• Metal-Dependent Reaction Tuning with Cyclopentylmetal Reagents: Application to the Asymmetric Synthesis of (+)-α-Conhydrine and (<i>S</i>)-2-Cyclopentyl-2-phenylglycolic Acid
  作者：Siddharth Roy、Anubha Sharma、Soumyaditya Mula、Subrata Chattopadhyay

  DOI：10.1002/chem.200801603

  日期：2009.2.2

  The reaction of halocyclopentane organometallic reagents can be tuned by the choice of metal (see scheme). Cyclopentylmagnesium bromide reduces aldehydes and ketones to the corresponding alcohols. However, in the presence of ZnCl2, normal Grignard addition to the ketones gives tertiary alcohols with complete diastereoselectivity. These protocols were used in the asymmetric synthesis of two medicinally

  调整：卤环戊烷有机金属试剂的反应可通过选择金属来调整（参见方案）。环戊基溴化镁将醛和酮还原为相应的醇。然而，在存在ZnCl 2的情况下，向酮中常规的格利雅（Grignard）加成会产生具有完全非对映选择性的叔醇。这些规程用于两种医学上重要的化合物的不对称合成。
• Stereoselective addition of Grignard reagents to sulfinimines derived from tartrate diol (threitol): Generation of chiral building blocks for the collective total synthesis of lentiginosine, conhydrine and methyldihydropalustramate
  作者：Kavirayani R. Prasad、Vipin Ashok Rangari

  DOI：10.1016/j.tet.2019.130496

  日期：2019.9

  tartaric acid diol was undertaken. It was observed that the chirality of the inherent tartrate moiety influences the diastereoselectivity of the resultant sulfinamides formed in the reaction. The formed products serve as excellent building blocks for the synthesis of natural products. This has been demonstrated in the collective total synthesis of lentiginosine, (+)-α-conhydrine and methyldihydropalustramate

  对将格氏试剂添加到源自酒石酸二醇的亚磺胺中进行了系统的研究。观察到，固有酒石酸部分的手性影响反应中形成的亚磺酰胺的非对映选择性。形成的产品是合成天然产品的极好基础。这已在龙胆草碱，（+）-α-水合柠檬酸和甲基二氢palustramate的集体全合成中得到了证明。
• Asymmetric synthesis of erythro- and threo-2-(1-hydroxyalkyl)piperidines via iodocyclocarbamation of 1-acyl-2-alkenyl-1,2,3,6-tetrahydropyridines
  作者：Daniel L Comins、Alfred L Williams

  DOI：10.1016/s0040-4039(00)00298-7

  日期：2000.4

  An iodocyclocarbamation procedure has been developed for the stereoselective preparation of erythro- and threo-2-(1-hydroxyalkyl)piperidines. This methodology was utilized in the asymmetric synthesis of two piperidine alkaloids, (+)-α-conhydrine and (+)-β-conhydrine.

  已经开发了碘代氨基甲酸酯化方法用于立体选择性制备赤型和苏型-2-（1-羟烷基）哌啶。该方法被用于两个哌啶生物碱（+）-α-水合和（+）-β-水合的不对称合成中。
• Enantioselective Synthesis of (+)-α-Conhydrine and (-)-Sedamine by L-Proline-Catalysed α-Aminooxylation
  作者：Tanveer Mahamadali Shaikh、Arumugam Sudalai

  DOI：10.1002/ejoc.201000169

  日期：——

  An efficient organocatalytic approach to the enantioslective synthesis of two important piperidine alkaloids, namely (+)-α-conhydrine (98 % ee) and (-)-sedamine (95 % ee), by L -proline-catalysed α-aminooxylation of aldehydes has been developed. The strategy involves an intramolecular cyclization to construct the piperidine core.

  一种有效的有机催化方法，通过 L-脯氨酸催化的醛的 α-氨基氧基化，对映选择性合成两种重要的哌啶生物碱，即 (+)-α-conhydrine (98% ee) 和 (-)-sedamine (95% ee)已经被开发出来。该策略涉及分子内环化以构建哌啶核心。
• Stereoselective Total Synthesis of (-)-β-Conhydrine and (+)-α-Conhydrine
  作者：Jose Vicario、Dolores Badía、Efraim Reyes、Nerea Ruiz、Luisa Carrillo

  DOI：10.1055/s-0030-1258390

  日期：2011.2

  carried out the stereoselective synthesis of (-)-β-conhydrine and (+)-α-conhydrine, two bioactive α-hydroxyalkyl-substituted piperidines, using the commercially available and inexpensive amino alcohol (S,S)-(+)-pseudoephedrine as chiral auxiliary. The key step of this synthesis relies on new methodology previously developed in our group, consisting of the chemo- and dia­stereoselective addition of Grignard

  我们已经使用市售和廉价的氨基醇（S，S）-（+）进行了两种生物活性被α-羟烷基取代的哌啶（-）-β-conhydrine和（+）-α-conhydrine的立体选择性合成-伪麻黄碱作为手性助剂。该合成的关键步骤依赖于先前在我们小组中开发的新方法，包括通过衍生自（S，S）-（+）-伪麻黄碱的α-亚氨基乙二酰乙酰胺的C = N键在化学和非对映选择性地添加格氏试剂然后将有机锂试剂选择性单加成到氨基甲酰基上，导致形成对映体富集的α-氨基酮。 不对称合成-手性助剂-哌啶-全合成-联苯