JPS58150596A - Deoxysarcophine - Google Patents

Abstract

NEW MATERIAL:16-Deoxysarcophine shown by the formula. USE:A calcium-antagonist, usable as a vasodilator or antispasmodic. PROCESS:For example, Sarcophyton sp., a kind of molluskan coral, is homogenized and extracted with a solvent such as methanol, etc., and fractionated by column chromatography, to give a compound shown by the formulaI.

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to Motoya-Hirodeoxynarcophyy Wlc.

Matters--There are various types of care such as OSm.
When the sexual substance is in the filament, the soft body is saro.
It was discovered that a type O diterpene found in ophymon has a calcium antagonistic effect.

In other words, it is well known that O muscle tissue such as the smooth muscle central muscle of the blood vessels and midintestinal tract of mammals becomes excited and contracts in winter due to the action of calcium ions (0-''). o
It is also known that t* bulky organic compounds (organic bases) exhibit the effect of suppressing excitation and contraction by specifically antagonizing these effects of C&1+ ions, and such compounds Calcium packed antiill (Oa-amtmgo
As mentioned above, the anti-calcicum antidrug known as nlst) suppresses, for example, the excitation and constriction of blood vessels, and is therefore used as a drug for vasodilation and anti-inflammatory treatment.

This research focuses on Umiokikomonomono, and contains raw S active substances in O and ζro, and a type of soft Nango (1&r@0ph7t).
On sp,), we confirmed the presence of 16-deo-ditylcophin (/4-4・o!ysaroophhln*)Q, which has the following formula (1) 0 steric structure and exhibits a clear calcium antagonistic effect. Succeed in doing so, and accomplish the final death. In other words, Motoya tII#OII! According to the mK theory of the present invention, ib-deoxynarcofin is present in 14-deoxynarcofin represented by the formula (1). A line r where the planar structure was 1m-11
The real materiality, the soft-bodied Nango〇 type (ilar...ph7t, nsp,) is hodginized, and the 11 far**s medium is layered and extracted. It can be isolated by fractionation using chromatography [I Motoya @ O Materials, as shown in the examples below, the melting point is 77 ~
1℃ (uncorrected), circular dichroism (Ol)) Svetator (methanol)
It does not show the tton effect, its ultraviolet (EFT) absorption spectrum (methanol) has no maximum absorption than Joonym, and its infrared (XR) a absorption spectrum (Klr) is Jtoo.

/410. /* Reference 0, /JIO1140 and Ida0 steel-1, and also Pron) IMK, Carbon M
MRI call! It was confirmed from the results of soot vector determination that it was a /6-deoxyf k :2 fin, and its three-dimensional structure was determined by X-ray analysis. 14 of the present invention
-Thio. As shown in the references below, XyIF'' and A/Fine exhibit excellent calcium antagonistic effects and are used as vasodilators and analgesics.

Hereinafter, the present invention will be described in more detail with reference to Examples.

Example: A type of coral (laroophyzon sp.) lj 01 was crushed and crushed into soft shells taken from a coral reef area off the coast of the main island of Okinawa, and then crushed using 900 methanol.
The extract was evaporated to dryness under reduced pressure below SOυ. Dry matter-! ,41,Wed/00114
After repeating the partitioning three times using a mixed solvent of 100 IIJ of ethyl acetate and 100 IIJ of ethyl acetate, the ethyl acetate layer was taken out and evaporated to dryness under reduced pressure below θ°C. Dry solids 7.61, n
- Silica, gel (K・1−・1g・16
Q1Merck, 70~JJ0 Metsushiz) J 00
1 was packed and applied to 9 columns (length 200 mm, diameter JO mm), the effluent was dispersed in Jvast portions and the activity was examined, and after the start of the flow, 1000 ~ / 1601 t of active content was evaporated to dryness under reduced pressure below aOO. Hardened. Dry solids J, jtl in a small lid O
Dissolve the precipitated crystals, /I, again in the n-column, and leave at room temperature.
Colorless prismatic crystals produced 0. t jF was obtained. The melting point of this substance is 77~det"0 (uncorrected), and the OD spectrum (KBr) is λ900, /, Aj
O,/reference uO1/310.140 and t#0es-”
Kll yield was shown.

The mass spectrum of this substance is 30K (M”) (calculated value date '1@'IQO!: JOJ), specific optical rotation [α
] +/j70 (0=/, 0.methanol). In addition, lHNMR (ODOAm 270 MHg) is
δt,oo(iH,rm)1,ko? (JH, 8), 840 (JH%S), 84 j (J if.

a), 8A ~/, 7 (koi!, m), 813 (21
1,a),i,t-λ,0(IH,m), ,2.
/J (IH, In), J, Jsan (IH, m), J, Jt
(JH, m), 2. sll (IH, m), -0 Riichi (
/H% 1% J-da,jHg), da,j(koH%
be), s, it (IH,!II), j, J, 7
(IH, dL% 10hm), s, z+<iH,
Otori) was 0. Also “OMMB (ODOLhJj,
J Mlig) is 170. a(q), /l,z(
q), /3.4((1)% /7.o (q), aJ
, s ($), as, J (c), Ko! , /(1χ34,
ri(su, Jri, 4 (t), Jt, t(t,), It
,t(c),48de(L),? L4! (S, tJ, t
((1), /J, 7.4 (1), /J4.J(A),
lcore,l(Hatake),/,yJ,a(s),/,74.
7 (S, /J?,,J(ri).Furthermore, the three-dimensional structure of this substance, that is, /4-deoxysarcophine, was determined by X@ analysis.The stereo projection image of 0 lines is #!
Figure 1 is as shown in Figure 1.Reference example (pharmacological test) [Experimental method]
After exsanguination, the leg aorta was removed and cut into margins, and Taleb Ringer (Kr. M-Rlng) was killed.
・Magnus (Mag) with a capacity of -01Lt containing r>m liquid
nu・) Good marking in the tube. The nutrient solution was kept at J7°,
91% O.

-j% 00. was ventilated. A resting tension of /1 was applied to this artery section, and an inkjet V
M / (inoubaszon) L9 @ Record the changes in the isodominant contraction on the sickle needle via the transducer.
Shie. In the example, each 110111t'c# & 916-zooxysarcofin was added to the nutrient solution, and! The effects of OL and noradrenaline on contractile anti-EhK should be investigated.

-) Effect on removed digestive tract of guinea pigs Male guinea pigs (kojio~aooit) were killed, and after exsanguination, the intestines and colon margins were removed according to the standard method.The nutrient solution was
Using Ringer's solution, keeping the temperature at Juo, 9 j f
k Oa-5 rice cake 00. was ventilated. This isoneutral property was recorded via a transducer. In addition, the 16-deoxysarcophine isolated in the example was uniformly used with various tIkK, and the effect on the contractile response by caroachol was evaluated.・Coffin using raw saline solution,
Is Gum Arabic S Swimming and Max's Weight -61 Yup
O,/Make &C#4 to administer the wound. Judgment of life and death was made at the same time. For Max, I used +14i type Naginei, and for Body 1, I used around 209.

〔Experimental result〕

16-deoxysarcophine (hereinafter referred to as this substance) was found in the rabbit's thoracic aorta, which was removed from wedlock.
Ilf dependence in tDIlkWIWc
The contraction reaction caused by K was suppressed, and in JX10″″1M, it was completely suppressed. In addition, to-'No@WVC had almost no effect on the contractile response caused by 10"M noradrenaline. Based on these findings, this study
This substance increases the influx of external fluid Oa'' into smooth muscle cells. This substance competitively competes with Oa flowing into smooth muscle cells by depolarization caused by Kot%'(Kot%'). Therefore, it is concluded that this substance is a drug with calcium antagonistic action (Oa-antagonistic), which increases the blood vessel expansion of each woodcutter.
! Used as a medicine.

(b) This substance in the excised gastrointestinal tract of the guinea pig and the intestinal tract of the guinea pig / 0 = ~ 1o4
hi omfK rotate II [dependently 10" MV) inhibited the contraction response induced by carbachol, and 704M completely inhibited the contraction response. In addition, in isolated guinea pig colons, this substance suppressed the contraction response of 3X10" to 10"M. In III, the contraction reaction (sustaining contraction component) caused by 10" MO carbachol was suppressed in a setting-dependent manner, and in IO, it was suppressed by Sokozen. Therefore, this substance is used as an antiperspirant. (c) Acute toxicity to mice caused by intraperitoneal administration of X.

[Brief explanation of drawings]

This is a stereo projection of the favorite lb-deoxysarcophine. Applicant: Sanichi Kasei Korai Taishiki Co., Ltd. Benyoshi: Yo Hase, and one other person

Claims (1)

[Claims] (1) Formula 14-deo life sinar 4iy indicated by 1