(5R,6R,7S,8R,8aS)-6,7,8-三羟基-5-(羟基甲基)-1,5,6,7,8,8a-六氢咪唑并[1,2-a]吡啶-2,3-二酮 | 109944-15-2

• 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: (5R,6R,7S,8R,8aS)-6,7,8-三羟基-5-(羟基甲基)-1,5,6,7,8,8a-六氢咪唑并[1,2-a]吡啶-2,3-二酮
• 中文别名: 几夫碱
• 英文名称: kifunensine
• 英文别名: 1-deoxymannojirimycin；(+)-kifunensine；kifunensin；(5R,6R,7S,8R,8aS)-6,7,8-trihydroxy-5-(hydroxymethyl)-1,5,6,7,8,8a-hexahydroimidazo[1,2-a]pyridine-2,3-dione
• CAS: 109944-15-2
• 化学式: C₈H₁₂N₂O₆
• 分子量: 232.193
• InChiKey: OIURYJWYVIAOCW-PQMKYFCFSA-N

物化性质

• 熔点：
  >280°C
• 密度：
  1.85±0.1 g/cm3(Predicted)
• 溶解度：
  二次蒸馏水中的溶解度：50MM

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  130
• 氢给体数：
  5
• 氢受体数：
  6

安全信息

• 储存条件：
  -20°C

SDS

---

Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Kifunensine
CAS-No. : 109944-15-2
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

---

Section 2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP]
Eye irritation (Category 2)
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Warning
Hazard statement(s)
H319 Causes serious eye irritation.
Precautionary statement(s)
P305 + P351 + P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove
contact lenses, if present and easy to do. Continue rinsing.
Supplemental Hazard none
Statements
Other hazards - none

---

Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms : Hexahydro-6R,7S,8aS-trihydroxy-5R-(hydroxymethyl)-imidazo[1,2-a]
pyridine-2,3-dione
FR 900494
Formula : C8H12N2O6
Molecular Weight : 232,19 g/mol

---

Section 4. FIRST AID MEASURES
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Indication of any immediate medical attention and special treatment needed
no data available

---

Section 5. FIREFIGHTING MEASURES
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx)
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

---

Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure
adequate ventilation. Avoid breathing dust.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

---

Section 7. HANDLING AND STORAGE
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature: -20 °C
Specific end uses
no data available

---

Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested
and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
impervious clothing, The type of protective equipment must be selected according to the
concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).

---

Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
point
f) Initial boiling point and no data available
boiling range
g) Flash point no data available
h) Evaporation rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density no data available
n) Water solubility no data available
o) Partition coefficient: n- log Pow: -2,951
octanol/water
p) Autoignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

---

Section 10. STABILITY AND REACTIVITY
Reactivity
no data available
Chemical stability
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available

---

Section 11. TOXICOLOGICAL INFORMATION
Information on toxicological effects
Acute toxicity
no data available
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitization
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
no data available
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion May be harmful if swallowed.
Skin May be harmful if absorbed through skin. May cause skin irritation.
Eyes Causes eye irritation.
Signs and Symptoms of Exposure
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Additional Information
RTECS: Not available

---

Section 12. ECOLOGICAL INFORMATION
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
no data available
Other adverse effects
no data available

---

Section 13. DISPOSAL CONSIDERATIONS
Waste treatment methods
Product
Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with
an afterburner and scrubber. Offer surplus and non-recyclable solutions to a licensed disposal company.
Contaminated packaging
Dispose of as unused product.

---

Section 14. TRANSPORT INFORMATION
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

---

Section 15. REGULATORY INFORMATION
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
no data available
Chemical Safety Assessment
no data available

---

Section 16. OTHER INFORMATION
Further information
Copyright 2012 Co. LLC. License granted to make unlimited paper copies for internal use
only.
The above information is believed to be correct but does not purport to be all inclusive and shall be
used only as a guide. The information in this document is based on the present state of our knowledge
and is applicable to the product with regard to appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Corporation and its Affiliates shall not be held
liable for any damage resulting from handling or from contact with the above product. See
and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

制备方法与用途

生物活性

Kifunensine 是一种从放线菌 Kitasatosporia kifunense 9482 中分离得到的有效选择性抑制 I 类 α-mannosidases 的化合物，能够阻断 α-mannosidases I 对糖蛋白上甘露糖残基的修剪。Kifunensine 还能抑制内质网相关的蛋白质降解途径。

体外研究

Kifunensine 是从放线菌 Kitasatosporia kifunense 9482 中提取的一种生物碱，是 α-mannosidase I 的最有效抑制剂，能够阻断 N-糖苷链在 GlcNAc2 (Man8) 或 Man9GlcNAc2 (Man9) 阶段的合成。具体实验数据如下：

• 细胞系：表达人 IgG1 单克隆抗体的杂交瘤细胞。
• 浓度：2 μg/mL。
• 孵育时间：4 天。
• 结果：
  • 显著减少了Lensil 荚膜豆凝集素结合。
  • 在测试的所有抑制剂中，Kifunensine 是唯一能够产生含有寡甘露糖残基而没有岩藻糖的抗体的有效抑制剂。

体内研究

在 BALB/c 小鼠模型中进行了 Kifunensine 的体内研究：

• 动物模型：BALB/c 小鼠。
• 剂量：5 mg/kg。
• 给药方式：尾静脉注射。
• 结果：在为期 7 天的观察期内，接受或未接受 Kifunensine 治疗的细胞产生的抗 TEM B 单克隆抗体（B mAb）血清水平没有显著差异。

反应信息

• 作为反应物：
  描述：

  (5R,6R,7S,8R,8aS)-6,7,8-三羟基-5-(羟基甲基)-1,5,6,7,8,8a-六氢咪唑并[1,2-a]吡啶-2,3-二酮 、 (S)-(+)-2-甲基丁酸酐 在 吡啶 作用下， 生成 9-(2-(S)-butanoyl)kifunensine
  参考文献：
  名称：

  [EN] STABILE CONJUGATE
  [FR] CONJUGUÉ STABLE

  摘要：

  本发明揭示了一种共轭物。该共轭物可以用公式I表示：[D-O-L]n-T 公式I，其中D是荷载分子；O是所述荷载分子的氧原子；T是能够结合目标分子、细胞和/或组织的靶向单元；n至少为1。

  公开号：

  WO2021123506A1
• 作为产物：
  描述：

  2-[(氨基氧代乙酰基)氨基]-2-脱氧-1,3:4,5-二-O-(异丙亚基)-D-甘露醇 在 吡啶 、 chromium(VI) oxide 、 氨 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 25.5h， 生成 (5R,6R,7S,8R,8aS)-6,7,8-三羟基-5-(羟基甲基)-1,5,6,7,8,8a-六氢咪唑并[1,2-a]吡啶-2,3-二酮
  参考文献：
  名称：

  Synthesis of Kifunensine, an Immunomodulating Substance Isolated from a Microbial Source.

  摘要：

  从放线菌中分离出的新型免疫调节剂 Kifunensine (1)，是以 D-甘露胺为对映体，通过草酰胺-甲醛前体的双环化，以氨作为关键停滞物合成的。经证实，天然 kifunensine 的绝对立体化学结构为 D 形式。

  DOI：

  10.1248/cpb.39.1392

文献信息

• [EN] CONJUGATE<br/>[FR] CONJUGUÉ
  申请人：GLYKOS BIOMEDICAL OY

  公开号：WO2019243672A1

  公开（公告）日：2019-12-26

  A conjugate is disclosed. The conjugate may comprise a targeting unit for delivery to a tumour, and a glycosylation inhibitor for inhibiting glycosylation in the tumour, thereby decreasing the immunosuppressive activity of the tumour. The glycosylation inhibitor may be conjugated to the targeting unit.

  揭示了一种共轭物。该共轭物可能包括用于传递至肿瘤的靶向单元，以及用于抑制肿瘤中的糖基化的糖基化抑制剂，从而降低肿瘤的免疫抑制活性。糖基化抑制剂可以与靶向单元结合。
• 一种甘露糖苷酶抑制剂Kif unensine的合成方法
  申请人：天津国际生物医药联合研究院

  公开号：CN110256422A

  公开（公告）日：2019-09-20

  本发明提供了一种甘露糖苷酶抑制剂Kifunensine的合成方法廉价易得的L‑古洛糖酸‑γ‑内酯为起始原料，通过多步化学转化，高效地得到Kifunensine，反应整体收率较高，过程中使用的试剂廉价易得，且合成过程中多个步骤可以用一锅法投料，操作简便，具有较好的工业化前景。
• Process for preparing kifunensine intermediate and kifunensine therefrom
  申请人：Industrial Research Limited

  公开号：US20040063973A1

  公开（公告）日：2004-04-01

  A novel method for the preparation of a compound of formula (I) from an N-protected-D-mannosamine. A compound of formula (I) is a useful intermediate for the preparation of kiftnensine, a potent and selective mannosidase inhibitor. The method includes protecting the hydroxyl group at the C-6 position of an N-protected-D-mannosamine, to give a 6-O-protected-N-protected-D-mannosamine; reducing the C-1 anomeric carbon atom of the 6-O-protected-N-protected-D-mannosamine to give a 6-O-protected-N-protected-D-mannitol; protecting the four hydroxyl groups of the 6-O-protected-N-protected-D-mannitol; and removing the nitrogen atom protecting group and optionally removing the C-6 oxygen atom protecting group to give the compound of formula (I): 1 where R 1 and R 2 are each independently protecting groups which, together with the oxygen atoms to which they are attached, form a 5-, 6-, 7- or 8-membered ring; and R 3 is hydrogen or a protecting group.

  一种从N-保护-D-甘露胺制备式(I)化合物的新方法。式(I)化合物是制备基夫特尼辛的有用中间体，基夫特尼辛是一种有效且选择性的甘露糖苷酶抑制剂。该方法包括保护N-保护-D-甘露胺的C-6位置的羟基，得到一个6-O-保护的N-保护-D-甘露胺；还原6-O-保护的N-保护-D-甘露胺的C-1异构碳原子，得到一个6-O-保护的N-保护-D-甘露醇；保护6-O-保护的N-保护-D-甘露醇的四个羟基；去除氮原子保护基并可选择性地去除C-6氧原子保护基，得到式(I)化合物：其中R1和R2分别是保护基，它们与其附着的氧原子一起形成一个5、6、7或8-成员环；R3是氢或保护基。
• Total synthesis of (+)-kifunensine, a potent glycosidase inhibitor
  作者：Jacques Rouden、Tomas Hudlicky

  DOI：10.1039/p19930001095

  日期：——

  (+)-Kifunensine, a potent inhibitor of mannosidase I, has been synthesized in 13 steps from chlorobenzene by microbial oxygenation with Pseudomonas putida 39D and stereocontrolled peripheral functionalization of cis-3-chlorocyclohexa-3,5-dienediol 3.

  （+）-基夫南菌素，一种强效的I型甘露糖苷酶抑制剂，已通过13步合成，从氯苯出发，利用假单胞菌（Pseudomonas putida 39D）进行微生物氧化，并对顺式-3-氯环己二烯-3,5-二烯二醇（3.）进行立体控制的周边功能化。
• Structure of Kifunensine, a New Immunomodulator Isolated from an Actinomycete.
  作者：Hiroshi KAYAKIRI、Shigehiro TAKASE、Toshihiro SIBATA、Masashi HASHIMOTO、Toshiji TADA、Shigetaka KODA

  DOI：10.1248/cpb.39.1378

  日期：——

  The structure of kifunensine, a new immunomodulator produced by a strain of Kitasatosporia, has been estabilished as 1 on the basis of chemical and physicochemical evidence and X-ray crystallographic analysis. Kifunensine is unique both in its novel structure, containing a 4, 5-dioxoimidazolidine ring included in the bicyclic framework, and in its potent immunomodulating activity. It is a representative of a new class of 1, 5-iminopyranoses.

  kifunensine 是一种由 Kitasatosporia 菌株产生的新型免疫调节剂，基于化学和物理化学证据以及 X 射线晶体学分析，已确定其结构为 1。 Kifunensine 的独特之处在于其新颖的结构（双环框架中包含 4, 5-二氧代咪唑烷环）及其强大的免疫调节活性。它是新一类1, 5-亚氨基吡喃糖的代表。