顺式-1-BOC-4-羟基-D-脯氨酸甲酯 | 114676-69-6

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 脯氨酸类衍生物
• 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: 顺式-1-BOC-4-羟基-D-脯氨酸甲酯
• 中文别名: 顺式-1-N-叔丁氧羰基-4-羟基-D-脯氨酸甲酯；(2R,4R)-1-Boc-4-羟基吡咯烷-2-甲酸甲酯；BOC-顺式-4-羟基-D-脯氨酸甲酯
• 英文名称: (2R,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate
• 英文别名: 1-(tert-butyl) 2-methyl (2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxylate；(1N)-tert-butoxycarbonyl-(2R)-carbomethoxy-(4R)-hydroxypyrrolidine；methyl (2R,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate；N-(tert-butoxycarbonyl)-cis-4-hydroxy-D-proline methyl ester；methyl cis-1-boc-4-hydroxy-D-prolinate；(2R,4R)-4-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester；1-O-tert-butyl 2-O-methyl (2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxylate
• CAS: 114676-69-6
• 化学式: C₁₁H₁₉NO₅
• mdl: MFCD00797548
• 分子量: 245.276
• InChiKey: MZMNEDXVUJLQAF-HTQZYQBOSA-N

物化性质

• 熔点：
  76 °C
• 比旋光度：
  63° (C=1,EtOH)
• 沸点：
  335.2±42.0 °C(Predicted)
• 密度：
  1.216±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.818
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Methyl cis-1-Boc-4-hydroxy-D-prolinate
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

---

Section 3. Composition/information on ingredients.
Methyl cis-1-Boc-4-hydroxy-D-prolinate
Ingredient name:
CAS number: 114676-69-6

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.

---

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.
Storage: Store in closed vessels, refrigerated.

---

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.

---

Section 9. Physical and chemical properties
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C11H19NO5
Molecular weight: 245.3

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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.

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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.

---

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

N-Boc-cis-4-羟基-D-脯氨酸甲酯是一种不可切割的ADC连接物，用于合成抗体-药物偶联物(ADC)。它也是一种基于烷基链的PROTAC连接剂，可用于合成PROTAC[1]。

反应信息

• 作为反应物：
  描述：

  顺式-1-BOC-4-羟基-D-脯氨酸甲酯 在 咪唑 、 锂硼氢 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.67h， 生成 tert-butyl (2R,4R)-4-((tert-butyldimethylsilyl)oxy)-2-(methoxymethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  [EN] IMIDAZOLO INDAZOLE COMPOUNDS AS JAK INHIBITORS
  [FR] COMPOSÉS D'IMIDAZOLO-INDAZOLE UTILISÉS EN TANT QU'INHIBITEURS DE JAK

  摘要：

  本文提供的是公式(I)的化合物及其药学上可接受的盐，其中A、W、X、Y和Z在说明书中有定义。公式(I)的化合物及其药学上可接受的盐是Janus激酶（JAK）抑制剂。本文还提供了包含这些化合物的药物组合物；以及使用这些化合物治疗炎症和纤维化疾病，包括呼吸道疾病的方法。

  公开号：

  WO2022272020A1
• 作为产物：
  描述：

  L-羟基脯氨酸 在 乙酸酐 、 碳酸氢钠 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 水 、 丙酮 为溶剂， 反应 11.0h， 生成 顺式-1-BOC-4-羟基-D-脯氨酸甲酯
  参考文献：
  名称：

  脯氨酸编辑：合成功能和结构多样化肽的通用且实用的方法。 4-取代脯氨酸对肽内构象的立体与立体电子效应分析

  摘要：

  功能化脯氨酸残基具有多种应用。在此，我们描述了一种实用方法，即脯氨酸编辑，用于合成具有立体特异性修饰的脯氨酸残基的肽。通过标准固相肽合成法合成肽，以掺入 Fmoc-羟脯氨酸 (4R-Hyp)。以自动化方式，Hyp 羟基受到保护，并合成肽的其余部分。肽合成后，Hyp 保护基被正交去除，Hyp 被选择性修饰，生成取代的脯氨酸氨基酸，肽主链起到“保护”脯氨酸氨基和羧基的作用。在模型四肽 (Ac-TYPN-NH2) 中，4R-Hyp 通过 Mitsunobu、氧化、还原、酰化和取代反应立体定向转化为 122 个不同的 4-取代脯氨酰氨基酸，具有 4R 或 4S 立体化学。通过脯氨酸编辑合成的 4-取代脯氨酸包括掺入的结构化氨基酸模拟物（Cys、Asp/Glu、Phe、Lys、Arg、pSer/pThr）、识别基序（生物素、RGD）、诱导立体电子效应的吸电子基团（氟，硝基苯甲酸酯），用于异核 NMR

  DOI：

  10.1021/ja3109664

文献信息

• [EN] OXADIAZOLE COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS OXADIAZOLE QUI INHIBENT L'ACTIVITÉ DE LA BÊTA-SECRÉTASE, ET LEURS PROCÉDÉS D'UTILISATION
  申请人：COMENTIS INC

  公开号：WO2012054510A1

  公开（公告）日：2012-04-26

  The invention provides novel beta-secretase inhibitors and methods for their including methods of treating Alzheimer's disease.

  这项发明提供了新型β-分泌酶抑制剂以及它们的方法，包括治疗阿尔茨海默病的方法。
• Pyrrolidine derivatives
  申请人：——

  公开号：US20020049243A1

  公开（公告）日：2002-04-25

  The present invention relates to pyrrolidine derivatives and dimeric forms and/or pharmaceutically acceptable esters, and/or salts thereof. The compounds are useful as inhibitors of metalloproteases, e.g. zinc proteases, particularly zinc hydrolases, and which are effective in treating disease states are associated with vasoconstriction of increasing occurrences.

  本发明涉及吡咯烷衍生物及其二聚体形式和/或药用可接受的酯和/或盐。这些化合物可用作金属蛋白酶抑制剂，例如锌蛋白酶，特别是锌水解酶，对治疗与血管收缩增加发生相关的疾病状态有效。
• TBK/IKK INHIBITOR COMPOUNDS AND USES THEREOF
  申请人：Merck Patent GmbH

  公开号：US20160376283A1

  公开（公告）日：2016-12-29

  The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TBK/IKKε inhibitors.

  本发明涉及式I化合物及其药用可接受的组合物，用作TBK/IKKε抑制剂。
• Development of New Hydroxamate Matrix Metalloproteinase Inhibitors Derived from Functionalized 4-Aminoprolines
  作者：Michael G. Natchus、Roger G. Bookland、Biswanath De、Neil G. Almstead、Stanislaw Pikul、Michael J. Janusz、Sandra A. Heitmeyer、Erin B. Hookfin、Lily C. Hsieh、Martin E. Dowty、Charles R. Dietsch、Vikram S. Patel、Susan M. Garver、Fei Gu、Matthew E. Pokross、Glen E. Mieling、Timothy R. Baker、David J. Foltz、Sean X. Peng、David M. Bornes、Michael J. Strojnowski、Yetunde O. Taiwo

  DOI：10.1021/jm000246e

  日期：2000.12.1

  activity with sub-nanomolar potency for some enzymes. Modifications of the P1' portion of the molecule played a key role in affecting both potency and selectivity within the MMP family. Longer-chain aliphatic substituents in this region of the molecule tended to increase potency for MMP-3 and decrease potency for MMP-1, as exemplified by compounds 48-50, while aromatic substituents, as in compound 52, generated

  从氨基脯氨酸支架制备了一系列异羟肟酸酯，并测试了其作为基质金属蛋白酶（MMP）抑制剂的功效。据报道该系列的详细SAR是针对MMP家族中的5种酶，许多抑制剂（例如化合物47）具有广谱活性，某些酶具有亚纳摩尔的效力。分子P1'部分的修饰在影响MMP家族内的效能和选择性方面起着关键作用。如化合物48-50所示，在分子的该区域中的长链脂族取代基倾向于增加对MMP-3的效力而降低对MMP-1的效力，而如化合物52中的芳族取代基产生广谱抑制作用。该数据基于X射线晶体数据也被合理化。虽然体外经口吸收似乎不太可预测，但随着更长和更多亲水性取代基的出现，吸收率往往会降低。最后，使用骨关节炎的大鼠模型评估这些化合物的功效，并在它们的药代动力学和体内功效之间建立了直接联系。
• Synthesis and biological evaluation of 4-purinylpyrrolidine nucleosides
  作者：Mark L. Peterson、Robert Vince

  DOI：10.1021/jm00113a017

  日期：1991.9

  the enantiomeric L-prolinol guanine derivative (36). Lastly, the 6-(dimethylamino)purine analogue, 37, was coupled to N-(benzyl-oxycarbonyl)-p-methoxy-L-phenylalanine to provide, after deprotection, the novel puromycin-like analogue 39. The analogues 26-29, 36, and 39 were all evaluated for antitumor and, except for 39, for antiviral activity. These compounds failed to appreciably inhibit the growth

  描述了几种新颖的碳氮杂嘌呤核苷的合成，这些碳氮杂嘌呤核苷结合了氮代替环戊基部分的碳3。这些类似物均来自关键的立体化学定义的中间体N-（叔丁氧羰基）-O-[（4-甲氧基苯基）二苯甲基]-反-4-羟基-D-脯氨醇（19），总含量为61.1％从顺-4-羟基-D-脯氨酸开始的五步序列的收率。通过与三苯基膦和偶氮二羧酸二乙酯的Mitsunobu型偶联过程，将杂环碱6-氯嘌呤和2-氨基-6-氯嘌呤有效地引入吡咯烷环上。标准转化和去除保护基团得到顺式腺嘌呤（26），次黄嘌呤（27），2,6-二氨基嘌呤（28）和鸟嘌呤（29）D-脯氨醇衍生物。此外，反式-4-羟基-L-脯氨酸的相关序列提供了对映体L-脯氨醇鸟嘌呤衍生物（36）。最后，将6-（二甲基氨基）嘌呤类似物37与N-（苄氧基羰基）-对甲氧基-L-苯丙氨酸偶联，以在脱保护后提供新的嘌呤霉素样类似物39。类似物26-29。分别评估了36、36和39的抗