シノメニン 化学特性,用途語,生産方法
解説
C19H23NO4(329.40)．シノメニンは，ツヅラフジ科オオツヅラフジSinomenium acutumの根茎に含まれるモルヒネ型アルカロイド．無色の針状晶．融点161 ℃．[α]D"－71°(エタノール)．エタノール，アセトン，クロロホルムに可溶，水，エーテル，ベンゼンに難溶．立体的にはモルヒネと対称の絶対配置をもっている．LD50 580 mg/kg(マウス，経口)．森北出版「化学辞典（第2版）
説明
Isolated by Ohta from Cocculus diversifolius DC., this alkaloid forms colourless
crystals from MeOH. It is stated to possess a powerful reflex action and to be aspasm stimulant, finally causing paralysis and death in toxic doses. It is also said
to suppress the hypotensive action of dihydroxyphenylethanolethylamine.
物理的性質
Appearance: acicular crystals (crystallized from benzene). Solubility: soluble in
ethanol, acetone, chloroform, and dilute alkali; slightly soluble in water, ether, and
benzene. Melting point: 219–221?°C. Specific optical rotation:?– 71° (c?=?2.1, ethanol). Its hydrochloride, crystallization (water or ethanol), decomposed at 278?°C.?Its
hydroiodide, needle crystal (crystallized from water), decomposed at 272?°C.?Its
picrate, which is yellow needle crystal, decomposed at 176?°C.?Sinomenine is sensitive to light and heat to decompose.
来歴
The chemical structure of sinomenine is composed of four rings, A, B, C, and D, similar to the structure of morphine. Ring A is a benzene ring, and ring B
is a half-chair-shaped, six-member ring. The C ring is a twisted-chair-type, sixmember ring that has an a, β-unsaturated ketone structure attached to the B ring. The
D ring is a nitrogen-containing, sixmember ring under the B ring. Its structure is
shown below; the current structural modification of sinomenine is mainly focused
on the A/C active group.
Based on the transformation of the A ring, it was found that the 1-substituted
formyl derivative of sinomenine showed the strongest inhibitory effect on the
inflammatory response of the mouse ear. The 4-substituted p-chlorobenzoyl-sinomenine has the strongest anti-inflammatory and analgesic activity. The biotransformation and chemical synthesis were also used to prepare the di-sinomenine
derivatives linked by carbon and carbon, which was stronger than that of sinomenine and had a strong inhibitory effect on cell inflammatory factors. Sinomenine
derivatives of the C ring with a pyrazine ring have a strong inhibitory effect on T, B
lymphocyte proliferation reaction, which can be used for the preparation of immunomodulatory drugs. The transformation of C ring carbonyl yielded a series of shift
alkali derivatives, with strong anti-inflammatory and analgesic effects. These
attempts are important for the development of new drugs.
使用
weak abortifacient, immunosuppressant, analgesic, antiinflammatory; LD50 (po) 580 mg/kg; (ip) 285 mg/kg(mouse)
適応症
It is mainly used for the treatment of rheumatoid arthritis and other types of rheumatism and arrhythmia in clinical.
生物活性
Natural anti-inflammatory morphinan analog. Causes degranulation of mast cells in mammalian tissues to release histamine and suppresses production of proinflammatory cytokines. Also displays antinociceptive activity, possibly through activation of the μ -opioid receptor. Stimulates short-term renewal of human embryonic stem cells (ESCs) in vitro .
臨床応用
The treatment of rheumatism and rheumatoid arthritis is one of the most important
clinical applications of sinomenine. Sinomenine is particularly suitable for the treatment of arrhythmia caused by organic heart disease. Sinomenine is used for the
treatment of glomerular disease, which can reduce urinary protein and relieve
hematuria symptoms, and the side effects were significantly lower than that of
tripterygium glycoside tablets, which are commonly used in clinical practice. In
addition, sinomenine can significantly inhibit renal interstitial fibrosis and the production of tissue growth and growth factor TGF-β1. Sinomenine can significantly
delay the development of chronic renal failure and effectively treat ankylosing
spondylitis.
純化方法
Crystallise the salt from water (1g/1.5mL) or EtOH. The free base [115-53-7] M 329.4, has m 161o (from EtOH) (and again at 182o) after crystallisation from *C6H6, and [] D -78.9o (c 1, EtOH). The picrate has m 159-162o(dec) (from H2O). [Beilstein 21 II 470, 21 III/IV 6670.]
参考文献
Ohta., Ber. ges. Physiol., 33, 352 (1925)
Ohta, Kitasato., Arch. expo Med., 6, 259, 283 (1925)
Raymond-Hamet., Compt. rend. Soc. Biol., 125, 509 (1937)
シノメニン 上流と下流の製品情報
原材料
準備製品