JPH01258679A - Heptacyclic alkaloid - Google Patents
Heptacyclic alkaloidInfo
- Publication number
- JPH01258679A JPH01258679A JP8319088A JP8319088A JPH01258679A JP H01258679 A JPH01258679 A JP H01258679A JP 8319088 A JP8319088 A JP 8319088A JP 8319088 A JP8319088 A JP 8319088A JP H01258679 A JPH01258679 A JP H01258679A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- heptacyclic
- alkaloid
- give
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229930013930 alkaloid Natural products 0.000 title abstract description 5
- 150000003797 alkaloid derivatives Chemical class 0.000 title abstract description 4
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 abstract description 14
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 abstract description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002904 solvent Substances 0.000 abstract description 6
- 208000003351 Melanosis Diseases 0.000 abstract description 3
- 238000004440 column chromatography Methods 0.000 abstract description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 3
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 210000004881 tumor cell Anatomy 0.000 abstract description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000001629 suppression Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 229940125904 compound 1 Drugs 0.000 description 10
- 229940125782 compound 2 Drugs 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229940126214 compound 3 Drugs 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 238000000862 absorption spectrum Methods 0.000 description 4
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 4
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 3
- OWNAOHKBXODWEL-UHFFFAOYSA-O 116302-36-4 Chemical compound C1CC2=CNC(C(C(N3)=C45)=O)=C2C5=[N+]1C1(O)C(=O)C=C2SC3CC42C1 OWNAOHKBXODWEL-UHFFFAOYSA-O 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 238000001142 circular dichroism spectrum Methods 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000002196 fr. b Anatomy 0.000 description 2
- 210000003918 fraction a Anatomy 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229930188118 prianosine Natural products 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- UKUVVAMSXXBMRX-UHFFFAOYSA-N 2,4,5-trithia-1,3-diarsabicyclo[1.1.1]pentane Chemical compound S1[As]2S[As]1S2 UKUVVAMSXXBMRX-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101100172748 Mus musculus Ethe1 gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 230000000397 acetylating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は新規な７環性アルカロイドに間するものである
。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a novel heptacyclic alkaloid.
（発明の目的）
本発明者等は各種の海産動物中に含まれる生理活性物質
を探索中のところ、沖縄海域に棲息するある種の海綿か
ら分離された新規な物質の構造を解明し、かつこの物質
が優れた抗腫瘍活性を示すことを確認し本発明を達成し
た。(Purpose of the Invention) The present inventors are searching for physiologically active substances contained in various marine animals, and have elucidated the structure of a new substance isolated from a type of sponge that lives in the waters of Okinawa. The present invention was achieved by confirming that this substance exhibits excellent antitumor activity.
（目的を達成するための手段）
本発明の詳細な説明するに、本発明における前示［１］
式で示される７環性アルカロイドは、何れも文献未載の
新規物質であって、例えば、Ｒ１及びＲ２が夫々水素原
子であって、Ｒ３がヒドロキシル基である化合物（化合
物ｌという）；Ｒ１、Ｒ２及びＲ３が共に水素原子であ
る化合物（化合物２という）；Ｒ１及Ｕ’ Ｒ２が共に
アセチル基であって、Ｒ３がアセトキシ基である化合物
（化合物３という）；Ｒ１及びＲ２が共にアセチル基で
あって、Ｒ３が水素原子である化合物（化合物４という
）等が挙げられる。(Means for achieving the object) For detailed explanation of the present invention, the foregoing [1] of the present invention
The heptacyclic alkaloids represented by the formula are all new substances that have not been described in literature, for example, a compound in which R1 and R2 are each a hydrogen atom and R3 is a hydroxyl group (referred to as compound 1); R1, Compounds in which R2 and R3 are both hydrogen atoms (referred to as compound 2); R1 and U' R2 are both acetyl groups, and R3 is an acetoxy group (referred to as compound 3); R1 and R2 are both acetyl groups. Examples include a compound in which R3 is a hydrogen atom (referred to as compound 4).
これ等のうち、化合物１及び化合物２は、沖縄海域に棲
息する、ある種の海綿プリアノスメラノス（なおｌ四牡
七１井）から分離することができる、また化合物３及Ｕ
化合物４は夫々、化合物１及び化合物２から誘導するこ
とができる。Of these, Compound 1 and Compound 2 can be isolated from a kind of sponge Prianosmelanos (NaoI Shio Shichiichii) that lives in the waters of Okinawa, and Compound 3 and U
Compound 4 can be derived from Compound 1 and Compound 2, respectively.
化合物ｌ及び化合物２は、上記プリアノス メラノスを
破砕してホモジナイズし、適当な溶媒を用いて抽出処理
し、ざらにカラムクロマトグラフィーにより精製するこ
とによフて単離することができる。また、化合物３及び
化合物４は夫々、化合物１及び化合物２を、例えばピリ
ジンのような溶媒中で無水酢酸を用いてアセチル化する
ことによって得ることができる。Compound 1 and Compound 2 can be isolated by crushing and homogenizing the Prianos melanos, extracting it using an appropriate solvent, and purifying it roughly by column chromatography. Further, Compound 3 and Compound 4 can be obtained by acetylating Compound 1 and Compound 2, respectively, using acetic anhydride in a solvent such as pyridine.
本発明の［１］の化合物の構造は、後記実施例に示すよ
うに、比旋光度、ＩＲ吸収スペクトル、Ｕｖ吸収スペク
トル、マススペクトル、ＩＨＮＭＲならびに＋３ＣＮＭ
Ｒ等により確認された。The structure of the compound [1] of the present invention is determined by specific rotation, IR absorption spectrum, Uv absorption spectrum, mass spectrum, IHNMR and +3CNM, as shown in the examples below.
Confirmed by R et al.
（実施例）
以下、本発明を実施例及び参考例を挙げて更に詳細に説
明する。(Examples) Hereinafter, the present invention will be explained in more detail by giving examples and reference examples.
実施例１
沖縄海域で採集した海綿プリアノス メラノス（匣（１
）」Ｌｌ」）９００ ｇ（湿重量）を破砕してホモジナ
イズし、１５００ ｍｌのメタノール／トルエン混合液
（３：１）を用いて室温で２回抽出した後、抽出液をＩ
Ｍの食塩水１５００ ｍｌを用いて２回抽出処理し、ト
ルエン層と水層に分離した。Example 1 Sponge Prianos melanos (box (1
)"Ll") 900 g (wet weight) was crushed and homogenized, extracted twice with 1500 ml of methanol/toluene mixture (3:1) at room temperature, and the extract was extracted with I.
The mixture was extracted twice using 1500 ml of M brine, and separated into a toluene layer and an aqueous layer.
水層を５００１のクロロホルムを用いて２回抽出し、ク
ロロホルム層を減圧下濃縮し乾固した。得られた残渣を
少量のクロロホルムに溶解してシリカゲル（“ワコーゲ
ルＣ−３００”和光純薬社製）を充填したカラム（３ｘ
６０ ｃ＋＋）に吸着させ、クロロホルム／メタノー
ル混合液（９０：１０〜８０：２０）を用いて溶出した
。最初から１２１０〜１９００ ｍｌの溶出画分（画分
Ａという）と２１１０〜２６６０ ｍｌの溶出画分（画
分Ｂという）とを採取し、夫々減圧下濃縮し乾固した。The aqueous layer was extracted twice using 5001 chloroform, and the chloroform layer was concentrated under reduced pressure to dryness. The obtained residue was dissolved in a small amount of chloroform, and a column (3x
60 c++) and eluted using a chloroform/methanol mixture (90:10 to 80:20). From the beginning, an eluted fraction of 1210 to 1900 ml (referred to as fraction A) and an eluted fraction of 2110 to 2660 ml (referred to as fraction B) were collected, and each was concentrated to dryness under reduced pressure.
画分Ａの残渣を少量のクロロホルム／メタノール混合液
（１：１）に溶解して“セファデックスＬ）Ｉ−２０”
（ファルマシア社！りのカラム（３Ｘ９０ ｃｍ）を用
い、メタノール／クロロホルム混合液（１：１）を展開
溶媒としてゲル濾過を行ない、２４０〜２６０ ｍｌの
活性画分を採取し、減圧下濃縮し乾固して化合物１を緑
色固体として得た。これをプリアノシンＣと命名した。The residue of fraction A was dissolved in a small amount of chloroform/methanol mixture (1:1) and prepared as "Sephadex L) I-20".
(Gel filtration was performed using a Pharmacia Co., Ltd. column (3 x 90 cm) using a methanol/chloroform mixture (1:1) as a developing solvent, and 240 to 260 ml of active fraction was collected, concentrated under reduced pressure, and dried. Solidification gave Compound 1 as a green solid, which was named Prianosine C.
一方、前記画分Ｂの残渣を少量のクロロホルム／メタノ
ール混合液（１：１）に溶解して“セファデックスＬＨ
−２０”のカラム（３Ｘ９０ ｃｍ）を用い、メタノー
ル／クロロホルム混合液（１：１）を展開溶媒としてゲ
ル濾過を行ない、２５０〜２７０ ｍｌの活性画分を採
取し、減圧下濃縮し乾固して化合物２を緑色固体として
得た。これをプリアノシンＤと命名した。Meanwhile, the residue of fraction B was dissolved in a small amount of chloroform/methanol mixture (1:1) to prepare "Sephadex LH".
Gel filtration was performed using a -20" column (3 x 90 cm) using a methanol/chloroform mixture (1:1) as a developing solvent, and 250 to 270 ml of active fraction was collected and concentrated under reduced pressure to dryness. Compound 2 was obtained as a green solid, which was named Prianosine D.
前記で得た化合物ｌ（プリアノシンＣ）２５−ｇを、無
水酢酸２１及びピリジン２１の混合液に加え、室温で一
夜閏反応させた後、蒸発乾固し、残渣をシリカゲル（和
光純薬社１！ Ｃ−３００）のカラム（ＩＸ １０ｃｍ
）を使用し、メタノール・クロロホルム（１：９９）を
溶出液としてカラムクロマトグラフィーにより精製して
４．６ ｍｇの化合物３を得た。また、前記で得た化合
物２（プリアノシンＤ）２５＋ｇｇを、無水酢酸及びと
リジンの混合液に加え、上記と同様にアセチル化を行な
った後、精製して１４．６ ｍｇの化合ｖＲ４を得た。25-g of the compound 1 (prianosine C) obtained above was added to a mixture of 21 acetic anhydride and 21 pyridine, and the mixture was reacted overnight at room temperature, and then evaporated to dryness. !C-300) column (IX 10cm
) and purified by column chromatography using methanol/chloroform (1:99) as an eluent to obtain 4.6 mg of Compound 3. In addition, 25+gg of the compound 2 (prianosine D) obtained above was added to a mixture of acetic anhydride and lysine, acetylated in the same manner as above, and purified to obtain 14.6 mg of compound vR4. .
化合物１〜化合物４の融点、比旋光度、Ｕ■吸収スペク
トル（ＵＶ）、ＩＲ吸収スペクトル（ＩＲ）、円二色性
スペクトル（ＣＤ）、マススペクトル（ＦＡＢＭＳ、Ｅ
ＩＭＳ）、ＩＮ ＮＭＲ及び＋３ＣＮＭＲ等の測定結果
は次の通りであったｅ
化合物１
融点３００℃以上
［（！ ］２２ ＋３５８°（ｃ＝ｏ、ｏｔ、ＭｅＯＨ
）ＵＶ（ＭｅＯＨ）λ、、、 ２３１（Ｃ１２３００）
、２６３（３９００）、２９２（２＋００）笈び３７０
（１２８０）ｎ＠ＩＲ（にＯｒ）シｓ＊、＋３４００〜
３１００，２９４５．１６５０．１６３０゜１６００、
１５４０−、１５００．１４３０．１３２０． ！２２
０．１１８０．１１３０．１０９０ 。Melting point, specific rotation, U absorption spectrum (UV), IR absorption spectrum (IR), circular dichroism spectrum (CD), mass spectrum (FABMS, E
IMS), IN NMR, +3CNMR, etc. measurement results were as follows e Compound 1 Melting point 300°C or higher [(! ]22 +358° (c=o, ot, MeOH
) UV (MeOH) λ, 231 (C12300)
, 263 (3900), 292 (2+00) 370
(1280)n@IR(niOr)sis*, +3400~
3100, 2945.1650.1630°1600,
1540-, 1500.1430.1320. ! 22
0.1180.1130.1090.
＋０４０ 、９９０ 、８４５ 、８００及び７４０
ｃｍ−１ＣＤ（ＭｅＯＨ）λｅｘｔ ３５２（Δｔ
＋４１．１）、３０８（−１７，３）及び２５Ｂ（−４
３，３）ｔｖ
ＦＡＢＭＳ（ｇｌｙｃｅｒｏｌ） ｍＨｚ ３５４
（Ｍ會＋Ｈ）ＥＩＭＳ ｍＨｚ ３５３（Ｍ÷）、
３３８（Ｍ”−Ｈ２Ｏ）、２６６（Ｍ”−ＣａｈＯ５）
化合物２
融点３００℃以上
［ａ ］２６ ＋３４４°（ｃｍ０．０１ 、ＭｅＯＨ
ゝＵＶ（ＭｅＯＨ）λ、、、２５０（ε１８１００）、
２８４（１１１００）、３２５（６６００）及び３９２
（６９５０）ｎ、ＩＩＲ（にＯｒ）シ、、、３４００〜
３１００，２９４５．１６６０，１６３０゜！６００，
１５４０，１５００，１４３０，１３２０，１３００，
１２２０．１１８０．＋１３５゜１１１０．９８０及び
９００ ｃｍ−１ＣＤ（ＭｅＯ）Ｉ）λｅｘｔ ３６０
（Δｃ ＋４５．８）、３０４（−１１，５）及び２
５５（−３４，４）ｒｖ
ＦＡＢＭＳ（ｇｌｙｃｅｒｏｌ） ｙｇ／ｚ ３３
８（Ｍ會＋Ｈ）ＥＩＭＳ ｍＨｚ ３３７（Ｍ◆）、３
０４（Ｍ會−Ｈ５）及び２４９（Ｍ◆−Ｃ３ｒ４ｅｓ）
化合物３
融点２００〜２０＋’Ｃ（分解）
［α］２３ ＋３８４°（Ｃ＝Ｏ，１，ＣＨＣｌ３）Ｕ
Ｖ（ＭｅＯＨ）入−ｏｘ ２４５（ε２１０００）、
２７９（＋７０００）、３７０（３２００）及び４１９
（２８００）。。+040, 990, 845, 800 and 740
cm-1CD(MeOH)λext 352(Δt
+41.1), 308 (-17,3) and 25B (-4
3,3) tv FABMS (glycerol) mHz 354
(M meeting + H) EIMS mHz 353 (M÷),
338 (M”-H2O), 266 (M”-CahO5)
Compound 2 Melting point: 300°C or higher [a ] 26 +344° (cm0.01, MeOH
ゝUV (MeOH) λ, 250 (ε18100),
284 (11100), 325 (6600) and 392
(6950)n, IIR(niOr)shi...3400~
3100, 2945. 1660, 1630°! 600,
1540, 1500, 1430, 1320, 1300,
1220.1180. +135°1110.980 and 900 cm-1CD(MeO)I)λext 360
(Δc +45.8), 304 (-11,5) and 2
55(-34,4)rv FABMS (glycerol) yg/z 33
8 (M meeting + H) EIMS mHz 337 (M◆), 3
04 (M-H5) and 249 (M◆-C3r4es) Compound 3 Melting point 200-20+'C (decomposition) [α]23 +384° (C=O,1,CHCl3)U
V (MeOH) containing-ox 245 (ε21000),
279 (+7000), 370 (3200) and 419
(2800). .
ＩＲ（ＫＢｒ）し、、、３５００〜３２００ 、３０９
０ 、２９２５ 、２８５０ 。IR (KBr), 3500-3200, 309
0, 2925, 2850.
＋７４０．１６５０．１５７０．１３７０．１３１０．
１２４０．１１８０．１１５０．１０５０゜１０３０
、９９０ 、９００ 、８４５ 、８００及び７４０
ｃｍ−１ＦＡＢＭＳ（ｇｌｙｃｅｒｏｌ） ｒａ／ｚ
４８０（Ｍ÷＋■）ＥＩＭＳ ｍＨｚ ４７９（Ｍ
◆）、４３７（Ｍ”−２Ａｃ−１（）、３５２（Ｍ＋−
３Ａｃ）。+740.1650.1570.1370.1310.
1240.1180.1150.1050°1030
, 990 , 900 , 845 , 800 and 740
cm-1 FABMS (glycerol) ra/z
480 (M÷+■) EIMS mHz 479 (M
◆), 437(M”-2Ac-1(), 352(M+-
3Ac).
３０８（Ｍ争−２Ａｃ−ＣａＨ２０Ｓ）及び２６６（３
０Ｂ−ＡＣ）１）Ｉ ＮＭＲ（ＣＤＣＩａ）δ２．２４
（Ｓ、Ｍｅ）、２．３２（ｄｄ、Ｊ＝１１．７及び４．
０ Ｈｚ、Ｌ７）、２．３４（ｓ、Ｍｅ）、２．４４（
ｄ、Ｊ＝１１．７ Ｈｚ、Ｈ−７）、２．５３（ｄ、Ｊ
＝１２．２ ）１ｚ、Ｈ−１）、２．５３（ｍ、Ｈ−
１７）、２．＋３３（ｓ。308 (M dispute-2Ac-CaH20S) and 266 (3
0B-AC)1)I NMR (CDCIa) δ2.24
(S, Me), 2.32 (dd, J=11.7 and 4.
0 Hz, L7), 2.34 (s, Me), 2.44 (
d, J = 11.7 Hz, H-7), 2.53 (d, J
=12.2)1z, H-1), 2.53(m, H-
17), 2. +33 (s.
Ｍｅ）、２．９３（ｍ、Ｊ＝１５．７，２．０及び１．
５ Ｈ２，Ｈ−１６）、３．０４（ｍ。Me), 2.93 (m, J=15.7, 2.0 and 1.
5 H2, H-16), 3.04 (m.
Ｊ＝１５．７，２．０及び４．８ Ｈｚ、Ｈ−１６）、
３．４５（ｄ、ＪＪ２．２ Ｈｚ。J=15.7, 2.0 and 4.8 Hz, H-16),
3.45 (d, JJ2.2 Hz.
Ｈ−１）、３．８３（ｄｄｄ、ｊ＝１２．５，４．８及
び２．ＯＨ２，Ｈ−１７）。H-1), 3.83 (ddd, j=12.5, 4.8 and 2.OH2, H-17).
５．９８（ｓ、Ｈ−４）、６．８８（ｄ、Ｊ＝１．５
Ｈｚ、Ｈ−１４）、７．０３（ｄ、Ｊ＝４．０ Ｈ
ｚ、Ｈ−８）、１０．８０（ｓ、Ｉｆ−ＯＨ）＋３ｃ
ＮＭＲ（ＣＤＣｌ２）６２１．４（Ｑ）、２２．２（
ｔ、Ｃ−１６）、２３．４（Ｑ）、２３．５（Ｑ）、３
２．７０（ｔ、Ｃ−１）、４２．７（Ｓ及びｔ、Ｃ−６
及びＣ・７）、４７．９（ｔ、Ｃ−１７）、６４．７（
ｄ、Ｃ−８）、８８．６（Ｓ、Ｃ−２）。5.98 (s, H-4), 6.88 (d, J=1.5
Hz, H-14), 7.03 (d, J=4.0 H
z, H-8), 10.80(s, If-OH)+3c
NMR (CDCl2) 621.4 (Q), 22.2 (
t, C-16), 23.4 (Q), 23.5 (Q), 3
2.70 (t, C-1), 42.7 (S and t, C-6
and C・7), 47.9(t, C-17), 64.7(
d, C-8), 88.6 (S, C-2).
′１１１．８（ｓ、Ｃ−２０）、１１５．０（ｄ、Ｃ−
５）、１１７．６（ｄ、Ｃ−１４）。'111.8 (s, C-20), 115.0 (d, C-
5), 117.6 (d, C-14).
Ｈ８，８（ｓ、Ｃ−１５）、１１９．５（ｓ、Ｃ−２１
）、１２０．４（ｓ、Ｃ−１０）。H8,8 (s, C-15), 119.5 (s, C-21
), 120.4 (s, C-10).
１２３．９（８，Ｃ−１２）、１２６．６（Ｓ、Ｃ−１
９）、１３３．６（Ｓ、Ｃ−１１）。123.9 (8, C-12), 126.6 (S, C-1
9), 133.6 (S, C-11).
１６９．４（ｓ、２−０（０）、１７１．０（ｓ、９−
ＮＧＯ）、１７３．１（Ｓ、１３−ＮＧＯ）、１７４．
８（ｓ、Ｃ−５）及び１８１．０（ｓ、Ｃ−３）化合物
４
融点２５６〜２５９℃（分解）
［α］２５ ＋３４１” （ｃ＝０．０３．Ｃ）ＩＣｈ
）ＩＪＶ（ＭｅＯＨ）入、１．２４７（ε１９７００）
、２８０（１７６００）及び３５０（４４００）ｎｍ
ＩＲ（にＯｒ）シ□、３５００〜３２００，３１２５，
２９２５，２８５０゜１６６０、＋６４０．１６１５，
１５７０，１４８０，１４２０，１３８０．１３００，
１２７０゜１１４０．９９０及び７４０ ｃｍ−１ＦＡ
ＢＭＳ（ｇｌｙｃｅｒｏｌ）ｍＨｚ ４２２（Ｍ◆＋
Ｈ）ＥＩＭＳ ｍＨｚ ４２１（Ｍ◆）、３７９（
ＭナーＡＣ）、３４６（Ｍ÷−Ａｃ−５Ｈ）。169.4(s, 2-0(0), 171.0(s, 9-
NGO), 173.1 (S, 13-NGO), 174.
8 (s, C-5) and 181.0 (s, C-3) Compound 4 Melting point 256-259°C (decomposition) [α]25 +341” (c=0.03.C) ICh
) IJV (MeOH) included, 1.247 (ε19700)
, 280 (17600) and 350 (4400) nm IR (or) □, 3500-3200, 3125,
2925, 2850°1660, +640.1615,
1570, 1480, 1420, 1380.1300,
1270°1140.990 and 740 cm-1FA
BMS (glycerol) mHz 422 (M◆+
H) EIMS mHz 421 (M◆), 379 (
Mner AC), 346 (M÷-Ac-5H).
３３６（Ｍ會−２Ａｃ−Ｈ）２９２（Ｍ會−ＡＣ−Ｃ３
Ｈ３Ｏ５）及び２５０（２９２−Ａｃ）ＩＨＮＭＲ（Ｃ
ＤＣＩａ）δ２．２１（ｄｄ、Ｊ＝１１．５及び３．８
）１ｚ、）Ｉ−７）、２．３０（ｓ、ＣＨ３Ｃ０）、
２．３４（ｄｄ、Ｊ＝１２．９及び３．０ Ｈｚ、Ｈ−
１）、２．４５（ｄ、Ｊ”１１．５ Ｈｚ、）Ｉ−７）
、２．５２（ｄｄＪ＝１２．９及び３．０ Ｈｚ、Ｈ
−１）、２．５３（ｓ、ＣＨｓＣＯ）、２．８９（ｍ、
Ｈ−１６）、２．９５（＋＊ 、 Ｈ−１７） 、 ３
．０６（ｍ 、 ）Ｉ −１６） 、 ３．３７（ｄｄ
ｄ 、 Ｊ＝ １２．０ 、４．９及びｆ、５ Ｈｚ、
）Ｉ−１７）、３．８６（ｔ、Ｊ−３，０Ｈｚ。336 (M-kai-2Ac-H) 292 (M-kai-AC-C3
H3O5) and 250(292-Ac) IHNMR (C
DCIa) δ2.21 (dd, J=11.5 and 3.8
)1z,)I-7), 2.30(s, CH3C0),
2.34 (dd, J=12.9 and 3.0 Hz, H-
1), 2.45 (d, J”11.5 Hz,)I-7)
, 2.52 (ddJ=12.9 and 3.0 Hz, H
-1), 2.53 (s, CHsCO), 2.89 (m,
H-16), 2.95 (+*, H-17), 3
．． 06(m, )I-16), 3.37(dd
d, J = 12.0, 4.9 and f, 5 Hz,
) I-17), 3.86 (t, J-3,0Hz.
Ｌ２）、５．９８（ｓ、）Ｉ−４）、６．８１（ｄ、Ｊ
＝２．０ Ｈｚ、Ｈ−１４）、６．９９（ｄ、Ｊ＝３
．８ Ｈｚ、Ｈ−８）、１０．６８（ｓ、１ｌ−ＯＨ
）＋３ＣＮＭＲ（ＣＤＣＩｓ）δ２２．３（ｔ、Ｃ−１
６）、２３．４（ｑ、ｃＨｓｃＯ）。L2), 5.98 (s, ) I-4), 6.81 (d, J
=2.0 Hz, H-14), 6.99(d, J=3
．． 8 Hz, H-8), 10.68 (s, 1l-OH
)+3CNMR(CDCIs)δ22.3(t,C-1
6), 23.4 (q, cHscO).
２３．５（ｑ、Ｃ）ＩｓＣＯ）、２９．５（ｔ、Ｃ−１
）、４３．０（ｔ、Ｃ−７）、４５．０（ｓ。23.5(q,C)IsCO), 29.5(t,C-1
), 43.0 (t, C-7), 45.0 (s.
Ｃ−６）、４８．０（ｔ、Ｃ−１７）、６０．３（ｄ、
Ｃ−２）、６４．６（ｄ、Ｃ−８）。C-6), 48.0 (t, C-17), 60.3 (d,
C-2), 64.6 (d, C-8).
１１０．７（ｓ、Ｃ−２０）、１１６．４（ｄ、Ｃ−４
）、１１７．６（ｄ、Ｃ−１４）。110.7 (s, C-20), 116.4 (d, C-4
), 117.6 (d, C-14).
１１８．７（Ｓ、Ｃ−１５）、１１９．０（ｓ、Ｃ−２
１）、１２０．９（Ｓ、Ｃ−１０）。118.7 (S, C-15), 119.0 (s, C-2
1), 120.9 (S, C-10).
１２３．６（ｓ、Ｃ−１２）、１２７．９（ｓ、Ｃ−１
９）、１３２．６（ｓ、Ｃ−１１）。123.6 (s, C-12), 127.9 (s, C-1
9), 132.6 (s, C-11).
１’７１．０（ｓ、ＣＨｓＣＯ）、１７３．３（８，Ｃ
ＨｓＣＯ）、１７６．３（ｓ、Ｃ−５）。1'71.0 (s, CHsCO), 173.3 (8, C
HsCO), 176.3 (s, C-5).
１８７．９（ｓ、Ｃ−３）
参考例
マウス白血病培！Ｉ纏胞に対するインビトロでの細胞毒
性試験
ローズウェルバーク メモリアル インスティチュート
培地（Ｒｏｓｅｗｅｌｌ Ｐａｒｋ Ｍｅａ＋ｏｒｉａ
ｌ ＩｎｓｔｉｔｕｔｅＭｅｄｉｕｍ）１６４０に、加
熱失活した牛胎児の血清をｌＯ％濃度で、またカナマイ
シンを５０μｇ／ｍｌｓ度で、夫々添加したものを細胞
の培養液として用いた。187.9 (s, C-3) Reference example mouse leukemia culture! In vitro cytotoxicity test against I cysts Rosewell Burke Memorial Institute medium (Rosewell Park Mea + oria
1 Institute Medium) 1640 to which heat-inactivated fetal bovine serum was added at a concentration of 10% and kanamycin at a concentration of 50 μg/ml, were used as a cell culture medium.
、各種の濃度の、実施例で得た化合物ｌ及び化合物２を
含む０．６％のＤＭＳＯ（ジメチルスルホキシド）溶液
１１に、マウス白血病培養細胞し１２１０及びし５１７
８Ｙを含む上記の培養液（５Ｘ １０４ ｃｅｌｌ／
ｍｌ）を加太、炭酸ガスのインキュベーター中にて３７
℃で４８時間培養した。Cultured mouse leukemia cells 1210 and 517 were added to 0.6% DMSO (dimethyl sulfoxide) solution 11 containing Compound 1 and Compound 2 obtained in Examples at various concentrations.
The above culture solution containing 8Y (5X 104 cells/
ml) in Kada in a carbon dioxide incubator.
The cells were cultured at ℃ for 48 hours.
抗！ｌ瘍活性は、ＩＣ５ａ［！Ｉ胞増殖の５０％を阻害
するのに必要な検体の濃度（μ８／１）で表す］の値に
より判定した。ＩＣ５ｇ値は、細胞の成長速度（コント
ロールの％）に対する化合物の濃度の対数値をプロット
することによって得られた。Anti! The tumor activity was determined by IC5a [! The concentration of the specimen required to inhibit 50% of I cell proliferation (expressed as μ8/1)] was determined. IC5g values were obtained by plotting the logarithm of compound concentration against cell growth rate (% of control).
その結果、マウス白血病培養細胞Ｌ１２１０及びＬ５１
７ＢＹに対する化合物ｌ及び化合物２のＩＣ５ｏ値は表
１通りであった。As a result, mouse leukemia cultured cells L1210 and L51
The IC5o values of Compound 1 and Compound 2 against 7BY were as shown in Table 1.
表 １
（発明の効果）
本発明の前示［１］式の７理性アルカロイドは、上記参
考例に示すように、マウス白血病培養細胞のような腫瘍
細胞株に対し優れた増殖阻止作用を示し、抗腫瘍剤とし
ての用途が朋待される。Table 1 (Effects of the Invention) As shown in the above-mentioned Reference Examples, the 7-rational alkaloid of formula [1] of the present invention exhibits an excellent growth-inhibiting effect on tumor cell lines such as mouse leukemia cultured cells, It is hoped that it will be used as an antitumor agent.
Claims (1)
１］ （式中Ｒ＾１及びＲ＾２は、夫々水素原子又はアセチル
基を示し、Ｒ＾３はヒドロキシル基、水素原子又はアセ
トキシ基を示す） で表わされる７環性アルカロイド。(1) The following formula [1] ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・・・・［
1] (wherein R^1 and R^2 each represent a hydrogen atom or an acetyl group, and R^3 represents a hydroxyl group, a hydrogen atom, or an acetoxy group).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8319088A JPH01258679A (en) | 1988-04-06 | 1988-04-06 | Heptacyclic alkaloid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8319088A JPH01258679A (en) | 1988-04-06 | 1988-04-06 | Heptacyclic alkaloid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01258679A true JPH01258679A (en) | 1989-10-16 |
Family
ID=13795403
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8319088A Pending JPH01258679A (en) | 1988-04-06 | 1988-04-06 | Heptacyclic alkaloid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01258679A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022518190A (en) * | 2019-01-09 | 2022-03-14 | ティ． ハーマン マーク | Synthetic novel pyrroloiminoquinone alkaloids and methods of use |
-
1988
- 1988-04-06 JP JP8319088A patent/JPH01258679A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022518190A (en) * | 2019-01-09 | 2022-03-14 | ティ． ハーマン マーク | Synthetic novel pyrroloiminoquinone alkaloids and methods of use |
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