JPH0242075A - 24-membered ring macrolide compound - Google Patents
24-membered ring macrolide compoundInfo
- Publication number
- JPH0242075A JPH0242075A JP63190638A JP19063888A JPH0242075A JP H0242075 A JPH0242075 A JP H0242075A JP 63190638 A JP63190638 A JP 63190638A JP 19063888 A JP19063888 A JP 19063888A JP H0242075 A JPH0242075 A JP H0242075A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- membered ring
- formula
- ring macrolide
- macrolide compound
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 14
- 239000003120 macrolide antibiotic agent Substances 0.000 title claims abstract description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- 239000000126 substance Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000002904 solvent Substances 0.000 abstract description 5
- 241000251557 Ascidiacea Species 0.000 abstract description 3
- 241001465754 Metazoa Species 0.000 abstract description 3
- 238000004440 column chromatography Methods 0.000 abstract description 3
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 241000251556 Chordata Species 0.000 abstract 1
- 241000826912 Eudistoma Species 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 229940125782 compound 2 Drugs 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 5
- 238000000862 absorption spectrum Methods 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 241000251555 Tunicata Species 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 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
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002955 isolation 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
- 239000007788 liquid Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（Ｍ梁上の利用分野）
本発明は新規な２４員環マクロライド化合物に間するも
のである。DETAILED DESCRIPTION OF THE INVENTION (Field of application on M beams) The present invention relates to novel 24-membered ring macrolide compounds.
（発明が解決しようとする問題点）
本発明者等は各種の海産動物体内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ホヤ
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。(Problems to be Solved by the Invention) The present inventors are currently searching for physiologically active substances contained in the bodies of various marine animals. The present invention was achieved by elucidating the substance and confirming that this substance exhibits excellent antitumor activity.
（問題点を解決するための手段）
本発明の詳細な説明するに、本発明の２４員環マクロラ
イド化合物としては、前記［１］式におけるＲが水素原
子である化合物（以下化合物ｌという）及び［１］式に
おけるＲがメチル基である化合物（以下化合物２という
）が挙げられ、これ等の化合物は何れも文献未載の新規
物質である。(Means for Solving the Problems) To explain the present invention in detail, the 24-membered ring macrolide compound of the present invention includes a compound in which R in the formula [1] is a hydrogen atom (hereinafter referred to as compound l). and a compound in which R in formula [1] is a methyl group (hereinafter referred to as compound 2), and all of these compounds are new substances that have not been described in any literature.
本発明の前記［１］式の２４員環マクロライド化合物は
、例えば後記実施例に示すように、ある種のホヤ（ｌ山
田ｗ ｃｆ−ｒｊ−■ム）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、カラムクロマトグラフ
ィーにより精製することによって単離することができ、
その構造は、後記実施例に示すように、それ等の比旋光
度、ＩＲ吸収スペクトル、ＵＶ吸収スペクトル、ＩＨ−
ＮＭＲ，１３Ｃ−ＮＭＲ及びマススペクトル等の測定結
果から確認される。The 24-membered ring macrolide compound of the formula [1] of the present invention can be obtained by crushing and homogenizing a type of sea squirt (l Yamada w cf-rj-), for example, as shown in the Examples below.
It can be isolated by extraction using an appropriate solvent and purification by column chromatography.
As shown in the examples below, their structures are as follows: their specific rotation, IR absorption spectrum, UV absorption spectrum, IH-
This is confirmed from measurement results such as NMR, 13C-NMR, and mass spectra.
なお、ホヤ類（Ａｓｃｉｄｉａｎ）は世界中の海域に棲
息し、系統発生的にはを索動物（Ｃｈｏｒｄａｔａ）に
分類され、生物学的に非常にユニークな性質を有する動
物である［化学と生物、第２３巻、第２号、１１９〜１
２３頁（１９８５年）、学会出版センター発行参照］。Ascidians live in oceans around the world, are phylogenetically classified as Chodata, and are animals with very unique biological properties [Chemistry and Biology, Volume 23, No. 2, 119-1
23 (1985), published by Gakkai Publishing Center].
（発明の効果）
本発明における前示［１］式の化合物は、後記参考例に
示すように、例えばマウス白血病培ａｍ胞Ｌ ５１？８
Ｙに対して優れた細胞毒性を示し、抗腫瘍剤としての用
途が期待される。(Effects of the Invention) The compound of the above formula [1] in the present invention can be used, for example, in mouse leukemia culture cell L51?8, as shown in the Reference Examples below.
It exhibits excellent cytotoxicity against Y and is expected to be used as an antitumor agent.
（実施例）
以下本発明を実施例について更に詳細に説明するが、本
発明は、その要旨を超えない限り、以下の実施例に制約
されるものではない。(Examples) Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples unless the gist thereof is exceeded.
実施例１ ［１］式の化合物の単離 沖縄伊江島の海域で採取したホヤ（ｌ…山」Ｃｆ。Example 1 [1] Isolation of compound of formula Sea squirt (l…yama) Cf collected in the sea area of Ie Island, Okinawa.
■訂進）１．６ ｋｇ（湿重量）を破砕してホモジナイ
ズし、２５００ ａｌｌ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、抽出液に１Ｍ食
塩水１２５０ ｍｌを加え、２０００ ｍｌのトルエン
を用いて４回抽出しトルエン層と水層に分離した。1.6 kg (wet weight) was crushed and homogenized, extracted twice at room temperature with 2500 all methanol/toluene mixture (3:1), and the extract was added with 1250 ml of 1M saline. was added and extracted four times using 2000 ml of toluene to separate into a toluene layer and an aqueous layer.
上記トルエン層２．５ｇを少量のクロロホルムに溶解し
、シリカゲル（フコ−ゲルＣ−３００，和光純薬社ｉり
を充填したカラム（２５Ｘ ４００ ｓｕｍ）に吸着さ
せ、クロロホルム／メタノール混合液（２，５：９７．
５）を展開溶媒として溶出させて最初から８５０〜９５
０１の溶出画分を採取し減圧下で濃縮乾固した。残渣を
更にシリカゲル（ワコーゲルＣ−３００）のカラム（１
５ｘ３００ ｍｎ＋）にかけて上記と同一の展開溶媒で
溶出させ、最初から２５０〜３４０ ｍｌｌｌ面出を採
取し減圧下で濃縮乾固した。2.5 g of the above toluene layer was dissolved in a small amount of chloroform and adsorbed on a column (25X 400 sum) packed with silica gel (Fuko-gel C-300, manufactured by Wako Pure Chemical Industries, Ltd.). 5:97.
5) as a developing solvent and 850 to 95 from the beginning.
The elution fraction of No. 01 was collected and concentrated to dryness under reduced pressure. The residue was further filtered through a silica gel (Wakogel C-300) column (1
5x300 mn+) and eluted with the same developing solvent as above, 250 to 340 ml of surface was collected from the beginning and concentrated to dryness under reduced pressure.
得られた残渣を少量のアセトニトリルに溶解し、逆相高
速液体カラムクロマトグラフィー［葺材化学社製Ｄｅｖ
ｅｌｏｓｉｌ ＯＤＳ、５μｎ＋、ＩＯＸ ２５０ ＋
ｕ＋１にかけ、アセトニトリル／水（８：２）を展開溶
媒として精製を行い、保持時間カ月８．３分及び２１．
６分の画分を採取し、夫々を減圧下で濃縮乾固して、保
持時間が１８．３分の画分から無色非結晶固体の化合物
１を、また保持時間２１．６分の画分から無色非結晶固
体の化合物２を得た。The obtained residue was dissolved in a small amount of acetonitrile, and subjected to reverse phase high performance liquid column chromatography [Dev manufactured by Fukizai Kagaku Co., Ltd.].
elosil ODS, 5μn+, IOX 250+
Purification was carried out using acetonitrile/water (8:2) as a developing solvent, and the retention time was 8.3 minutes and 21.
Fractions of 6 minutes were collected and each was concentrated to dryness under reduced pressure. Compound 1, a colorless amorphous solid, was obtained from the fraction with a retention time of 18.3 minutes, and colorless compound 1 was obtained from the fraction with a retention time of 21.6 minutes. Compound 2 was obtained as an amorphous solid.
化合物ｌ及び化合物２の融点、比旋光度、ＩＲ吸収スペ
クトル、Ｕｖ吸収スペクトル、ＩＨＮＭＲ。Melting point, specific rotation, IR absorption spectrum, Uv absorption spectrum, IHNMR of Compound 1 and Compound 2.
＋３ｃ ＮＭＲ及びマススペクトル（ＦＡＢＭＳ）の測
定結果は以下の通りであった。The measurement results of +3c NMR and mass spectrum (FABMS) were as follows.
化合物ｌ
融点ニア１〜７３℃
［α３２３ −３６．４° （ｃ Ｏ，１？、ＣｌＣｌ
５）Ｒ（ＣｌＣｌ３）ν、。、 ３３５０，２９２５．
２８５０．１？１５，１６００゜１５３０、１４５０．
１３８０．１２６０．１２２０．１１５０．１０８０．
９９０及び９７０ ｃｗ＋−１
ＵＶ（ＣＨａＯＨ）λｓｓ＋＋ ２３１（ε２７０００
）ｎｍＩＨＮＭＲ（ＣＤＣＩｓ）δ８．２９（Ｓ、ｂｒ
、Ｈ−３４） 、６．８５（ｗ＋、Ｈ−３３）、６．８
０（ｔ、Ｊ＝５．９ Ｈｚ、Ｈ−３０）、６．６２（ｄ
ｄ、Ｊ＝９．６及び１５．４Ｈｚ、Ｈ−３）、６．４７
（ｄ、Ｊ＝１５．５ Ｈｚ、Ｈ−１２）、６．２７（ｄ
、、１＝１０．９ Ｈｚ、Ｈ−２６）、６．１２（ｄ、
Ｊ＝１０．９ Ｈｚ、Ｈ−２７）、６．０２（ｍ。Compound l Melting point near 1-73°C [α323 -36.4° (c O,1?, ClCl
5) R(ClCl3)ν,. , 3350, 2925.
2850.1?15,1600゜1530, 1450.
1380.1260.1220.1150.1080.
990 and 970 cw+-1 UV (CHaOH) λss++ 231 (ε27000
) nm IHNMR (CDCIs) δ8.29 (S, br
, H-34), 6.85 (w+, H-33), 6.8
0 (t, J=5.9 Hz, H-30), 6.62 (d
d, J=9.6 and 15.4Hz, H-3), 6.47
(d, J=15.5 Hz, H-12), 6.27 (d
,,1=10.9 Hz, H-26), 6.12(d,
J=10.9 Hz, H-27), 6.02 (m.
２Ｈ，Ｈ−１９及びＨ−２０）、５．９０（ｄ、Ｊ＝１
５．５ Ｈｚ、Ｈ−６）、５．７１（ｄ、Ｊ＝１５．４
Ｈｚ、Ｈ−２）、５．５３（ｄｄｄ、Ｊ＝５．０，９
．４及び１５．５Ｈｚ、Ｈ−１１）、５．４５（ｄｄ、
Ｊ＝１５．５及び８．９ Ｈｚ、Ｈ−５）、５．４３（
ｄｄ、Ｊ＝１４．０及び５．ＯＨ２，）Ｉ−２１）、５
．４２（ｄｄ、Ｊ＝１４．６及び４．２ Ｈｚ、Ｈ−１
８）、５．２１（ｄｄ、Ｊ＝１０．７及び５．６ Ｈｚ
、Ｈ−１４）、５．１２（ｄ、Ｊ＝１０．０ Ｈｚ、
Ｈ−２３）、５．１１（ｄ、Ｊ＝９．６ Ｈｚ、Ｈ−８
）。2H, H-19 and H-20), 5.90 (d, J=1
5.5 Hz, H-6), 5.71 (d, J=15.4
Hz, H-2), 5.53 (ddd, J=5.0,9
．． 4 and 15.5Hz, H-11), 5.45 (dd,
J = 15.5 and 8.9 Hz, H-5), 5.43 (
dd, J=14.0 and 5. OH2,)I-21),5
．． 42 (dd, J=14.6 and 4.2 Hz, H-1
8), 5.21 (dd, J=10.7 and 5.6 Hz
, H-14), 5.12 (d, J=10.0 Hz,
H-23), 5.11 (d, J=9.6 Hz, H-8
).
４．５０（ｍ、Ｈ−３２）、４．１９（ｄｄ、Ｊ＝１０
及び２．６ Ｈｚ、）Ｉ−３５）。4.50 (m, H-32), 4.19 (dd, J=10
and 2.6 Hz, )I-35).
４．１４（ｄｄｄ、Ｊ＝２．７，９．６及び９．６ Ｈ
ｚ、Ｈ−９）、３．８９（ｄ、Ｊ＝５．９８２．Ｈ−２
９）、３．６５（１，Ｈ−３５）、３．３７（ＩＩＩ、
ＯＨ）、３．３３（ｎ＋。4.14 (ddd, J=2.7, 9.6 and 9.6 H
z, H-9), 3.89 (d, J=5.982.H-2
9), 3.65 (1, H-35), 3.37 (III,
OH), 3.33 (n+.
Ｈ−１７） 、３．２６（ｓ、 Ｈ−４１） 、３．０
４（ｓ 、 Ｈ−３９） 、２．９６（ｍ 、 Ｈ−４
） 。H-17), 3.26(s, H-41), 3.0
4 (s, H-39), 2.96 (m, H-4
).
２．６５（ｍ、Ｈ−１０）、２．５５（ｎ＋、２Ｈ，Ｈ
−１５及びＨ−２２）、２．３６（ｍ。2.65 (m, H-10), 2.55 (n+, 2H, H
-15 and H-22), 2.36 (m.
Ｈ−１０） 、２．０５（ｎ＋、ト１５） 、 １．８
０（ｓ、３Ｈ，Ｈ−４０） 、 １．７５（ｓ、３Ｈ。H-10), 2.05 (n+, 15), 1.8
0(s, 3H, H-40), 1.75(s, 3H.
Ｈ−３７）、１．６７（ｓ、６Ｈ，Ｈ−４２及びＨ−３
６）、１．６１（ｎ＋、Ｈ−１６）。H-37), 1.67(s, 6H, H-42 and H-3
6), 1.61 (n+, H-16).
１．３６（ｍ、Ｈ−１６）、１．１０（ｄ、Ｊ＝６．８
Ｈｚ、３Ｈ，Ｈ−４３）及び０．９３（ｄ、Ｃ６，８
Ｈｚ、ｔｌ−３８）＋３ＣＮＭＲ（ＣＤＣＩａ）６１７
０．６０（Ｓ、Ｃ−３１）、１６６．０９（ｓ。1.36 (m, H-16), 1.10 (d, J=6.8
Hz, 3H, H-43) and 0.93 (d, C6,8
Hz, tl-38) +3CNMR (CDCIa) 617
0.60 (S, C-31), 166.09 (s.
Ｃ−１） 、 １６１．６１（ｄ 、Ｃ−３４） 、
１５２．２４（ｄ 、Ｃ−３） 、 １３６．５４（ｓ
。C-1), 161.61(d, C-34),
152.24 (d, C-3), 136.54 (s
.
Ｃ−１３）、１３５．４７（ｄ、Ｃ−２１）、１３４．
５６（ｓ、Ｃ−２８）、１３３．７７（ｄ。C-13), 135.47 (d, C-21), 134.
56 (s, C-28), 133.77 (d.
Ｃ−６）、１３３．７２（Ｓ、Ｃ−７）、１３２．６８
（ｄ、Ｃ−１８）、１３１．９０（ｄ。C-6), 133.72 (S, C-7), 132.68
(d, C-18), 131.90 (d.
Ｃ−１９）、１３１．７５（ｄ、Ｃ−５）、１３１．０
０（ｓ、Ｃ−２５）、１３０．５１（ｄ。C-19), 131.75 (d, C-5), 131.0
0 (s, C-25), 130.51 (d.
Ｃ−８）、１２９．５４（ｄ、Ｃ−２０）、１２８．４
５（ｄ、Ｃ−１２）、１２８．４４（ｄ。C-8), 129.54 (d, C-20), 128.4
5 (d, C-12), 128.44 (d.
Ｃ−１４）、１２５．０４（ｄ、Ｃ−２６）、１２４．
５５（ｄ、Ｃ−１１）、１２１．１９（ｄ。C-14), 125.04 (d, C-26), 124.
55(d, C-11), 121.19(d.
Ｃ−２７）、１１８．９６（ｄ、Ｃ−２）、８２．６３
（ｄ、Ｃ−２３）、７９．６３（ｄ、Ｃ−１７）、７６
．６４（ｄ、Ｃ−９）、６２．２１（ｔ、Ｃ−３５）、
５６．１２（ｑ、Ｃ−３９）。C-27), 118.96 (d, C-2), 82.63
(d, C-23), 79.63 (d, C-17), 76
．． 64 (d, C-9), 62.21 (t, C-35),
56.12 (q, C-39).
５５．７１３（ｑ、Ｃ−４１）、５２．４１（ｄ、Ｃ−
３２）、４６．６４（ｔ、Ｃ−２９）。55.713 (q, C-41), 52.41 (d, C-
32), 46.64 (t, C-29).
４１．７３（ｄ、Ｃ−４）、４０．２０（ｄ、Ｃ−２２
）、３９．６９（ｔ、Ｃ’−１０）。41.73 (d, C-4), 40.20 (d, C-22
), 39.69 (t, C'-10).
３４．６７（ｔ、Ｃ−１６）、２２．７２（ｔ、Ｃ−１
５）、２１．２５（Ｑ、Ｃ−４３）。34.67 (t, C-16), 22.72 (t, C-1
5), 21.25 (Q, C-43).
２０．５７（ｑ、Ｃ−４０）、 １６．６０（ｑ、Ｃ−
３８）、 １４．９４（ｑ、Ｃ−４２）。20.57 (q, C-40), 16.60 (q, C-
38), 14.94 (q, C-42).
１２．９３（ｃ！、Ｃ−３６）及び１１．９７（Ｑ、Ｃ
−Ｃ−３７）ＦＡ８ ｖａ／ ｚ ７８４（Ｍ＋ジェ
タノールアミン＋■）令。12.93 (c!, C-36) and 11.97 (Q, C
-C-37) FA8 va/z 784 (M+getanolamine+■) order.
ｍ／ｚ ６７７（Ｍ−Ｈ）−；Ｍｒ ６７８化合物
２
融点二６９〜７１℃
［α１２３−１７．６’ （ＣＯ，１？、Ｃ）ＩＣｌ３
）＋Ｒ（ＣＤＣＩａ）νｓａｇ ３３５０．２９２５．
２８５０．１？１５，１６５０゜１５３０、１４５０．
１３８０．１２５０． ＋２２０．１１００．１０８０
．９９０及び９７０ ｃｍ＋−１
ＵＶ（（ＪＩｓＯＨ）λｓｅ＋＋ ２３５（ε２６００
０）ｎ１１＋１）Ｉ ＮＭＲ（ＣＤＣＩａ）δ８．２８
（ｓ、ｂｒ、Ｈ−３４）、６．８７（ｄ、Ｊ＝７．１
Ｈｚ、Ｈ−３３）、６．８０（ｔ、Ｊ＝５．９ Ｈｚ、
Ｈ−３０）、６．６２（ｄｄ、Ｊ＝１０．３及び１．４
）１ｚ、ト３）、６．４８（ｄ９．Ｉ”１５．７ ）
１ｚ、）ｌ−１２）。m/z 677(MH)-; Mr 678 Compound 2 Melting point 269-71°C [α123-17.6' (CO,1?, C)ICl3
)+R(CDCIa)vsag 3350.2925.
2850.1?15,1650°1530,1450.
1380.1250. +220.1100.1080
．． 990 and 970 cm+-1 UV ((JIsOH)λse++ 235(ε2600
0)n11+1)I NMR (CDCIa) δ8.28
(s, br, H-34), 6.87 (d, J=7.1
Hz, H-33), 6.80 (t, J=5.9 Hz,
H-30), 6.62 (dd, J=10.3 and 1.4
)1z, g3), 6.48 (d9.I"15.7)
1z,)l-12).
６．２８（ｄ、Ｊ＝１１．３ Ｈ２，ト２６）、６．１
３（ｄｄ、Ｊ＝１１．３及び０．９５ Ｈｚ、Ｈ−２７
）、６．０３（ｍ、２Ｈ，Ｊ＝１４．７及び１０．４
Ｈｚ、Ｈ−１９及びＨ−２０）、５．８６（ｄ、Ｊ＝１
５．５ Ｈｚ、Ｈ−６）、５．５１（ｄｄｄ、Ｊ＝４．
７，１０．５及び１５．７ Ｈｚ、Ｈ−１１）、５．５
６（ｄｄ、Ｊ＝１５．５．及び９．０ Ｈｚ、Ｈ−５）
、５．３９（ｄｄ、Ｊ＝１４．６及び４．２ Ｈｚ、Ｈ
−２１）、５．３８（ｄｄ、Ｊ＝１４．６及び５．５
Ｈｚ、Ｈ−１８）、５．１８（ｄｄ。6.28 (d, J=11.3 H2, g26), 6.1
3 (dd, J=11.3 and 0.95 Hz, H-27
), 6.03 (m, 2H, J = 14.7 and 10.4
Hz, H-19 and H-20), 5.86 (d, J=1
5.5 Hz, H-6), 5.51 (ddd, J=4.
7, 10.5 and 15.7 Hz, H-11), 5.5
6 (dd, J=15.5. and 9.0 Hz, H-5)
, 5.39 (dd, J=14.6 and 4.2 Hz, H
-21), 5.38 (dd, J=14.6 and 5.5
Hz, H-18), 5.18 (dd.
Ｊ＝ＩＯ，７及び５．６ Ｈｚ、Ｈ−１４）、５．１４
（ｄ、ＪＪｏ、ＯＨｚ、）Ｉ−２３）、５．０８（ｄ、
Ｊ＝９．３ Ｈｚ、Ｈ−８）、４．５１（ｍ、Ｈ−３
２）、４．２０（ｄｄ。J=IO, 7 and 5.6 Hz, H-14), 5.14
(d, JJo, OHz,)I-23), 5.08(d,
J = 9.3 Hz, H-8), 4.51 (m, H-3
2), 4.20 (dd.
Ｊ＝１１．４及び２．６ ）ＩＺ、Ｈ−３５）、４．１
２（ｄｄｄ、Ｊ＝２．６，９．３及び９．３ Ｈｚ、Ｈ
−９）、３．９０（ｄ、Ｊ＝５．５ Ｈｚ、Ｈ−２９）
、３．６５（ｍ。J=11.4 and 2.6) IZ, H-35), 4.1
2 (ddd, J=2.6, 9.3 and 9.3 Hz, H
-9), 3.90 (d, J=5.5 Hz, H-29)
, 3.65 (m.
、Ｈ−３５）、３．３７（ｍ、ＯＨ）、３．２７（爾、
Ｈ−１７）、３．２６（Ｓ、Ｈ−４１）。, H-35), 3.37 (m, OH), 3.27 (er,
H-17), 3.26 (S, H-41).
３．１５（ｍ、Ｈ−４）、２．９６（ｓ、Ｈ−３９）、
２．６８（ｍ、Ｈ−１０）、２．５５（ｗ＋。3.15 (m, H-4), 2.96 (s, H-39),
2.68 (m, H-10), 2.55 (w+.
ト２２及びＨ−１５）、２．３２（＋１．）ｌ、）ｌ−
１０）、１．９０（１，８−１５）。G22 and H-15), 2.32 (+1.)l, )l-
10), 1.90 (1,8-15).
１．８０（ｓ、Ｈ−４０）、１．７９（ｓ、Ｈ−４４）
、１．７７（ｓ、Ｈ−３７）、１．７５（Ｓ、Ｈ−３６
）、１．７４（ｓ、Ｈ−４２）、１．６２（１，Ｈ−１
６）、１．３２（１，Ｈ−１６）、１．０５（ｄ、Ｊ＝
６．８ Ｈ２，Ｈ−４３）及び０．９３（ｄ、Ｊ＝６．
８ Ｈｚ。1.80 (s, H-40), 1.79 (s, H-44)
, 1.77 (s, H-37), 1.75 (S, H-36
), 1.74 (s, H-42), 1.62 (1, H-1
6), 1.32 (1, H-16), 1.05 (d, J=
6.8 H2, H-43) and 0.93 (d, J=6.
8 Hz.
Ｈ−３８）
＋３ＣＮＭＲ（ＣＤＣＩａ）８１７０．２７（ｓ、Ｃ−
３１）、１６７．３９（ｓ。H-38) +3CNMR (CDCIa) 8170.27 (s, C-
31), 167.39 (s.
Ｃ−１）、１６１．５６（ｄ、Ｃ−３４）、１４５．４
１（ｄ、Ｃ−３）、１３６．７４（ｓ。C-1), 161.56 (d, C-34), 145.4
1 (d, C-3), 136.74 (s.
Ｃ−１３）、１３５．６９（ｄ、Ｃ−２１）、１３４．
５６（ｓ、Ｃ−２８）、１３３．１６（ｄ。C-13), 135.69 (d, C-21), 134.
56 (s, C-28), 133.16 (d.
Ｃ−６）、１３３．７２（ｓ、Ｃ−７）、１３２．９３
（ｄ、Ｃ−２５）、１３２．６７（ｄ。C-6), 133.72 (s, C-7), 132.93
(d, C-25), 132.67 (d.
Ｃ−１８）、１３０．７６（ｄ、Ｃ−２０）、１２９．
５２（ｄ、Ｃ−１２）、１２８．３７（ｄ。C-18), 130.76 (d, C-20), 129.
52(d, C-12), 128.37(d.
Ｃ−１４）、１２５．３３（ｓ、Ｃ−２）、１２４．９
９（ｄ、Ｃ−２６）、１２４．６１（ｄ。C-14), 125.33 (s, C-2), 124.9
9(d, C-26), 124.61(d.
Ｃ−１１）、１２１．２０（ｄ、Ｃ−２７）、８２．７
２（ｄ、Ｃ−２３）、す、５２（ｄ。C-11), 121.20 (d, C-27), 82.7
2 (d, C-23), Su, 52 (d.
Ｃ−１７） 、７ｓ、７ｏ（ｄ、Ｃ−９） 、６２．２
１（ｔ、Ｃ−３５） 、 ５６．９０（ｑ 、Ｃ−３９
）、５５．７４（Ｑ、Ｃ−４１）、５２．３９（ｄ、Ｃ
−３２）、４６．６５（ｔ、Ｃ・２９）、４０．６２（
ｄ、Ｃ−２２）、４０．４６（ｔ、Ｃ−１０）、３７．
８６（ｄ、Ｃ−４）。C-17), 7s, 7o(d, C-9), 62.2
1 (t, C-35), 56.90 (q, C-39
), 55.74 (Q, C-41), 52.39 (d, C
-32), 46.65 (t, C・29), 40.62 (
d, C-22), 40.46 (t, C-10), 37.
86 (d, C-4).
３４．７１（ｔ、Ｃ−１６）、２２．７６（ｔ、Ｃ−１
５）、２１．２６（ｑ、Ｃ−４３）。34.71 (t, C-16), 22.76 (t, C-1
5), 21.26 (q, C-43).
２０．５７（Ｑ、Ｃ−４０）、 １６．５７（Ｑ、Ｃ−
３８）、 １４．９３（Ｑ、Ｃ−３６）。20.57 (Q, C-40), 16.57 (Q, C-
38), 14.93 (Q, C-36).
１２．９２（ｑ 、Ｃ−４２） 、 １１．９７（Ｑ
、Ｃ−４４）及び１１．７７（Ｑ、Ｃ−Ｃ−４４）ＦＡ
Ｂ ｍ／ ｚ ７９Ｂ（Ｍ＋ジェタノールアミン＋■
）÷。12.92 (q, C-42), 11.97 (Q
, C-44) and 11.77 (Q, C-C-44)FA
B m/z 79B (M+jetanolamine+■
)÷.
ｍ／ ２６９１（Ｍ−Ｈ）−；Ｍｒ ６９２参考例１
［マウス白血病環１１細胞に対するインビトロでの細胞
毒性試験コ
ローズウェルパーク メモリアルインステイチュート培
地（Ｒｏｓｅｗｅｌｌ Ｐａｒｋ Ｍｅｍｏｒｉａｌ
ＩｎｓｔｉｔｕｔｅＭｅｄｉｕｍ）１６４０に、加熱失
活した牛胎児の血清を１０％濃度で、またカナマイシン
を５０μｇ／ａｌ１度で、夫々添加したものを細胞の培
養液として用いた。m/2691 (MH)-; Mr 692 Reference Example 1 [In vitro cytotoxicity test against mouse leukemia ring 11 cells Rosewell Park Memorial Institute medium (Rosewell Park Memorial
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/al, were used as a cell culture medium.
各種の濃度の実施例１で得た化合物１及び化合物２を含
む０．６％の［）ＭＳＯ（ジメチルスルホキシド）溶液
１１に、マウス白血病環！Ｉ纏胞Ｌ ５１７ＢＹを含む
上記の培養液（５Ｘ １０４ｃｅｌｌ／ｍｌ）を加え、
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。A mouse leukemia ring! Add the above culture solution (5X 104 cells/ml) containing I phthisis L 517BY,
The cells were cultured at 37° C. for 48 hours in a carbon dioxide gas incubator.
抗腫瘍活性は、ＩＣ５ｏ［細胞増殖の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。ＩＣ５ｏ、の値は、細胞の成長速度（コント
ロールの％）に対しする化合物１及び化合物２の濃度の
対数値をプロットすることにより得られた。Antitumor activity was determined by the value of IC5o [expressed as the concentration of analyte required to inhibit 50% of cell proliferation (μ8/1)]. IC5o values were obtained by plotting the logarithm of the concentrations of Compound 1 and Compound 2 against the cell growth rate (% of control).
その結果、マウス白血病環１１ｍ１Ｉａ Ｌ ５１７８
Ｙに対する化合物１及び化合物２のＩＣ５ｏ値は、夫々
２２ ｎｇ／＋ｓｌ及び１．０ ｎｇ／ｍｌであった。As a result, mouse leukemia ring 11m1Ia L 5178
The IC5o values of Compound 1 and Compound 2 against Y were 22 ng/+sl and 1.0 ng/ml, respectively.
Claims (1)
基を示す） で表わされる２４員環マクロライド化合物。(1) Formula [1] ▲There are mathematical formulas, chemical formulas, tables, etc.▼----[1] (In the formula, R represents a hydrogen atom or a methyl group, and Me represents a methyl group.) A 24-membered ring represented by Macrolide compounds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63190638A JPH0242075A (en) | 1988-08-01 | 1988-08-01 | 24-membered ring macrolide compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63190638A JPH0242075A (en) | 1988-08-01 | 1988-08-01 | 24-membered ring macrolide compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0242075A true JPH0242075A (en) | 1990-02-13 |
Family
ID=16261403
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63190638A Pending JPH0242075A (en) | 1988-08-01 | 1988-08-01 | 24-membered ring macrolide compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0242075A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0680958A1 (en) * | 1994-04-19 | 1995-11-08 | Arizona Board Of Regents | Isolation and structure of dictyostatin 1 and its use as anti-neoplastic agent |
| US6427300B2 (en) | 1999-07-23 | 2002-08-06 | Teijin Seiki Co., Ltd. | Yarn relaxation-heating method and apparatus therefor |
| WO2008113320A1 (en) * | 2007-03-22 | 2008-09-25 | Studiengesellschaft Kohle Mbh | Lejimalid analoga and uses thereof |
| US10106919B2 (en) | 2012-12-28 | 2018-10-23 | Kuraray Co., Ltd. | Drawing device and drawing method |
-
1988
- 1988-08-01 JP JP63190638A patent/JPH0242075A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0680958A1 (en) * | 1994-04-19 | 1995-11-08 | Arizona Board Of Regents | Isolation and structure of dictyostatin 1 and its use as anti-neoplastic agent |
| US6427300B2 (en) | 1999-07-23 | 2002-08-06 | Teijin Seiki Co., Ltd. | Yarn relaxation-heating method and apparatus therefor |
| WO2008113320A1 (en) * | 2007-03-22 | 2008-09-25 | Studiengesellschaft Kohle Mbh | Lejimalid analoga and uses thereof |
| US20100056616A1 (en) * | 2007-03-22 | 2010-03-04 | Studiengesellschaft Kohle Mbh | Iejimalid analoga and uses thereof |
| US8431724B2 (en) | 2007-03-22 | 2013-04-30 | Studiengesellschaft Kohle Mbh | Iejimalid analoga and uses thereof |
| US10106919B2 (en) | 2012-12-28 | 2018-10-23 | Kuraray Co., Ltd. | Drawing device and drawing method |
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