O-叔丁基-L-苏氨酸甲酯盐酸盐 | 71989-43-0

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 其他保护氨基酸
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: O-叔丁基-L-苏氨酸甲酯盐酸盐
• 中文别名: H-THR(TBU)-OME盐酸盐
• 英文名称: O-tert-butyl-L-threonine methyl ester hydrochloride
• 英文别名: H-Thr(t-Bu)-OMe*HCl；H-Thr(tBu)-OMe.HCl；methyl (2S,3R)-2-amino-3-[(2-methylpropan-2-yl)oxy]butanoate;hydrochloride
• CAS: 71989-43-0
• 化学式: C₉H₁₉NO₃*ClH
• mdl: MFCD00077111
• 分子量: 225.716
• InChiKey: SDHKEUUZUMQSAD-HHQFNNIRSA-N

物化性质

• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

• 辛醇/水分配系数(LogP)：
  0.63
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.888
• 拓扑面积：
  61.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• WGK Germany：
  3
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  2-8°C

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: H-Thr(tBu)-OMe HCl
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: H-Thr(tBu)-OMe HCl
CAS number: 71989-43-0

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, refrigerated.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C9H19NO3.ClH
Molecular weight: 225.7

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途

O-叔丁基-L-苏氨酸甲酯盐酸盐是一种苏氨酸衍生物，已被用于制备抗真菌环二肽哌替林。

制备

1. 取L-苏氨酸甲酯放入圆底烧瓶中，加入无水乙醇和转子。

2. 将圆底烧瓶置于硅油加热炉中，加热至80℃。待液体均匀后，分批加入氢氧化钾，反应约1小时，液体由浑浊变为透明。

3. 加入叔丁基锂，液体变为透明淡黄色，并继续反应2小时。此时液体颜色不变，通过薄层色谱检测反应进度。一旦L-苏氨酸甲酯完全反应，立即停止反应并冷却至室温后过滤，得到淡黄色粉末。

4. 在圆底烧瓶中加入无水二氧六环和转子。

5. 将L-苏氨酸甲酯悬浮于二氧六环溶液中，并与芴甲氧羰基叠氮进行酰化反应。通过薄层色谱检测反应进度，待O-叔丁基-L-苏氨酸完全反应后停止反应，得到粗品O-叔丁基-L-苏氨酸甲酯盐酸盐。

6. 在pH值为9-10的条件下用乙酸乙酯进行抽提，并经重结晶精制而得成品。

反应信息

• 作为反应物：
  描述：

  O-叔丁基-L-苏氨酸甲酯盐酸盐 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 lithium iodide 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 N-α-methyl-N-α-(o-nitrobenzenesulfonyl)-O-t-butyl-L-threonine
  参考文献：
  名称：

  与Fmoc固相肽合成兼容的N-甲基氨基酸的便捷合成

  摘要：

  Ñ α含甲基氨基酸肽表现出有趣的治疗概况和正日益被视为潜在的有用的治疗剂。不幸的是，它们的合成是由高价格和unavaibility的许多阻碍Ñ α甲基氨基酸。的有效且实用的制备Ñ α甲基ñ α - （ö -nitrobenzenesulfonyl）-α-氨基而不需要大量纯化的酸进行说明。该程序是基于公知的Ñ的烷基化Ñ α通过使用硫酸二甲酯和DBU作为碱改进的-芳基磺酰基氨基酯。酯裂解被有效地用S来实现Ñ与碘化锂2型皂化，避免与氢氧化锂水解观察到消旋。的合成的兼容性Ñ α甲基氨基羧酸与Fmoc固相肽合成是通过使用正常的偶合条件，以有效地制备证明ñ -甲基的二肽。所描述的过程允许制备Ñ α甲基氨基酸中的时间很短的时间和的快速合成Ñ使用Fmoc的固相肽合成-甲基肽。

  DOI：

  10.1021/jo050477z
• 作为产物：
  描述：

  N-[(苄氧基)羰基]-O-(2-甲基-2-丙基)-L-苏氨酸甲酯 在 钯 氢气 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 以88%的产率得到O-叔丁基-L-苏氨酸甲酯盐酸盐
  参考文献：
  名称：

  Synthesis of the amino-terminal decapeptide of human calcitonin, in which the disulfide bond is replaced by a thioether group

  摘要：

  一种全保护的氨基末端十肽Ib，其序列与人降钙素相同，其中S-S桥被S-CH2基团（所谓的7-碳代物）所取代，主要通过逐步法合成。线性十肽的环化是通过活性酯实现的。

  DOI：

  10.1135/cccc19801305

文献信息

• [EN] GLYCOGEN PHOSPHORYLASE INHIBITOR COMPOUND AND PHARMACEUTICAL COMPOSITION THEREOF<br/>[FR] COMPOSÉ INHIBITEUR DE LA GLYCOGÈNE PHOSPHORYLASE ET COMPOSITION PHARMACEUTIQUE CONTENANT LEDIT COMPOSÉ
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009045831A1

  公开（公告）日：2009-04-09

  This invention relates to a novel compound which is a glycogen phosphorylase inhibitor and its use in the treatment of diabetes and other conditions associated therewith. The invention further relates to a pharmaceutical composition containing the compound and to processes for preparing the compound and pharmaceutical composition.

  这项发明涉及一种新型化合物，它是一种糖原磷酸化酶抑制剂，以及其在治疗糖尿病和其他相关疾病中的用途。该发明还涉及含有该化合物的药物组合物，以及制备该化合物和药物组合物的方法。
• [EN] MONOCYCLIC N-ARYL HYDANTOIN MODULATORS OF ANDROGEN RECEPTOR FUNCTION<br/>[FR] MODULATEURS D'HYDANTOINE N-ARYL MONOCYCLIQUES DE LA FONCTION DU RECEPTEUR D'ANDROGENE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2005049580A1

  公开（公告）日：2005-06-02

  The present invention relates to novel compounds useful in the treatment of androgen receptor associated conditions, such as age-related diseases, pharmaceutical compositions containing at least one of the compounds of the present invention and methods of treating a patient in need of therapy for an androgen receptor associated condition by administering a therapeutically effective amount of at least compound of the present invention.

  本发明涉及一种新型化合物，用于治疗与雄激素受体相关的疾病，如与年龄相关的疾病，包含至少一种本发明化合物的药物组合物，以及通过给予至少一种本发明化合物的治疗有效量来治疗需要治疗雄激素受体相关疾病的患者的方法。
• Access to Enantiopure α-Hydrazino Acids for <i>N</i>-Amino Peptide Synthesis
  作者：Chang Won Kang、Matthew P. Sarnowski、Yassin M. Elbatrawi、Juan R. Del Valle

  DOI：10.1021/acs.joc.6b02718

  日期：2017.2.3

  amide substituents have received less attention due, in part, to the lack of practical synthetic strategies. Here, we report the synthesis of α-hydrazino acids derived from 19 out of the 20 canonical proteinogenic amino acids and demonstrate their use in the solid-phase synthesis of N-amino peptide derivatives.

  α-肽的骨干N-甲基化已被广泛用于增强亲本序列的生物利用度和生物活性。杂原子肽酰胺取代基受到的关注较少，部分原因是缺乏实用的合成策略。在这里，我们报告了20种典型蛋白氨基酸中19种衍生的α-肼基酸的合成，并证明了它们在N-氨基肽衍生物的固相合成中的用途。
• Chiral Arylated Amines via C−N Coupling of Chiral Amines with Aryl Bromides Promoted by Light
  作者：Geyang Song、Liu Yang、Jing‐Sheng Li、Wei‐Jun Tang、Wei Zhang、Rui Cao、Chao Wang、Jianliang Xiao、Dong Xue

  DOI：10.1002/anie.202108587

  日期：2021.9.20

  molecular Ni catalysis driven by light, which enables stereoretentive C-N coupling of optically active amines, amino alcohols, and amino acid esters with aryl bromides, with no need for any external photosensitizer. The method is effective for a wide variety of coupling partners, including those bearing functional groups sensitive to bases and nucleophiles, thus providing a viable alternative to accessing

  Buchwald-Hartwig CN 偶联反应已在有机合成中得到广泛应用。在过去二十年左右的时间里，已经引入了许多改进的催化剂，现在可以很容易地使用各种胺和芳基亲电试剂。然而，缺乏可用于偶联各种手性胺和芳基卤而不会侵蚀过量对映体 ( ee) 的方案）。本文报道了一种基于光驱动的分子 Ni 催化的方法，该方法能够使旋光胺、氨基醇和氨基酸酯与芳基溴进行立体保留 CN 偶联，无需任何外部光敏剂。该方法对多种偶联伙伴有效，包括那些带有对碱和亲核试剂敏感的官能团的偶联伙伴，从而为获取合成重要的手性N-芳基胺、氨基醇和氨基酸酯提供了可行的替代方案。92 个例子证明了它的可行性，ee高达 99% 。
• Late Stage Phosphotyrosine Mimetic Functionalization of Peptides Employing Metallaphotoredox Catalysis
  作者：Hao Chen、Runyu Mao、Martin Brzozowski、Nghi H. Nguyen、Brad E. Sleebs

  DOI：10.1021/acs.orglett.1c01200

  日期：2021.6.4

  requires multistep syntheses, and therefore late stage incorporation of these mimetics into peptides is not feasible. Here, we develop and employ metallaphotoredox catalysis using 4-halogenated phenylalanine to afford a variety of protected pTyr mimetics in one step. This methodology was shown to be tolerant of common protecting groups and applicable to the late stage pTyr mimetic modification of protected

  获得磷酸酪氨酸 (pTyr) 模拟物需要多步合成，因此将这些模拟物后期掺入肽中是不可行的。在这里，我们使用 4-卤代苯丙氨酸开发和使用金属光氧化还原催化，一步提供各种受保护的 pTyr 模拟物。该方法显示出对常见保护基团的耐受性，并适用于受保护和未受保护肽以及具有生物相关性的肽的后期 pTyr 模拟修饰。