JPH08109182A - Compound rp-1551s - Google Patents
Compound rp-1551sInfo
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- JPH08109182A JPH08109182A JP7208649A JP20864995A JPH08109182A JP H08109182 A JPH08109182 A JP H08109182A JP 7208649 A JP7208649 A JP 7208649A JP 20864995 A JP20864995 A JP 20864995A JP H08109182 A JPH08109182 A JP H08109182A
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pyrane Compounds (AREA)
Abstract
Description
【0001】[0001]
【発明の属する技術分野】本発明は、ペニシリウム(Pen
icillium) 属に属する微生物により生産され、抗菌作用
を有する化合物RP−1551類に関する。TECHNICAL FIELD The present invention relates to penicillium (Pen
icillium ), which is produced by a microorganism belonging to the genus icillium and has an antibacterial action.
【0002】[0002]
【従来の技術】後述するRP−1551類に類似した構
造を有する物質としては、式(VI)または式(VI
I)2. Description of the Related Art Substances having a structure similar to those of RP-1551s described later are represented by the formula (VI) or the formula (VI).
I)
【0003】[0003]
【化6】 [Chemical 6]
【0004】でそれぞれ表されるイソクロモフィロンI
(Isochromophilone I)またはイソクロモフィロンII
(Isochromophilone II )が、ジャーナル・オブ・アン
チビオチックス[(Journal of Antibiotics), 46, 1908
-1911 (1993)]に、ヒト免疫不全症ウイルス(HIV)
のエンベロープ蛋白であるgp120 と表面抗原CD4 との結
合を阻害する物質として報告されている。Isochromophyllon I represented by
(Isochromophilone I) or Isochromophilone II
(Isochromophilone II) [Journal of Antibiotics], 46 , 1908
-1911 (1993)], human immunodeficiency virus (HIV)
It has been reported as a substance that inhibits the binding between the surface antigen CD4 and the envelope protein gp120.
【0005】式(VIII)または式(IX)Formula (VIII) or Formula (IX)
【0006】[0006]
【化7】 [Chemical 7]
【0007】でそれぞれ表されるケトビリジンB(Chae
toviridin B )またはケトビリジンC(Chaetoviridin
C )がケミカル・ファーマシューティカル・ブレチン
[(Chemical & Pharmaceutical Bulletin), 38, 625-62
8 (1990)]に色素として報告されている。式(X)[0007] Ketoviridin B (Chae
toviridin B) or ketoviridin C (Chaetoviridin
C) refers to Chemical Pharmaceutical Bulletin [(Chemical & Pharmaceutical Bulletin), 38 , 625-62
8 (1990)] as a dye. Formula (X)
【0008】[0008]
【化8】 Embedded image
【0009】で表されるTL−3およびTL−4が第35
回天然有機化合物討論会(1993年10月11〜13日、京都;
講演要旨集 pp290〜297 )において色素として報告され
ている。上記化合物のうち、TL−3およびTL−4は
R1 およびR2 が一体となって式(II)を表す化合物
(RP−1551−1)と同一の平面構造を有するが、
8 位に対する 2' 位および5'位の相対立体配置に関し両
者は異なっている。TL-3 and TL-4 represented by
Annual Meeting of Natural Organic Compounds (October 11-13, 1993, Kyoto;
It is reported as a pigment in the abstracts of the lectures pp290-297). Of the above compounds, TL-3 and TL-4 have the same planar structure as the compound (RP-1551-1) in which R 1 and R 2 are united to represent the formula (II),
The two are different with respect to the relative configuration at the 2'and 5'positions with respect to the 8th position.
【0010】[0010]
【発明が解決しようとする課題】本発明の目的は、抗菌
活性を有する新規生理活性物質を提供することにある。An object of the present invention is to provide a novel bioactive substance having antibacterial activity.
【0011】[0011]
【課題を解決するための手段】本発明は、式(I)The present invention provides a compound of formula (I)
【0012】[0012]
【化9】 [Chemical 9]
【0013】{式中、R1 およびR2 は、(1)一体と
なって式(II){In the formula, R 1 and R 2 are (1) integrated into formula (II)
【0014】[0014]
【化10】 [Chemical 10]
【0015】(式中、2’位水素および5’位水素は8
位水素とそれぞれanti配置の関係にある)を表す
か、(2)R1 が水素を表し、R2 が式(III)(In the formula, 2'-position hydrogen and 5'-position hydrogen are 8
Position hydrogen and each have an anti-configuration) or (2) R 1 represents hydrogen and R 2 is of the formula (III)
【0016】[0016]
【化11】 [Chemical 11]
【0017】を表すか、(3)一体となって式(IV)Or (3) together form the formula (IV)
【0018】[0018]
【化12】 [Chemical 12]
【0019】を表すか、または(4)一体となって式
(V)Or (4) together represents the formula (V)
【0020】[0020]
【化13】 [Chemical 13]
【0021】を表す}で表される化合物RP−1551
類に関する。該化合物はペニシリウム属に属する微生物
を培養することにより得ることができる。Compound RP-1551
Regarding kind. The compound can be obtained by culturing a microorganism belonging to the genus Penicillium.
【0022】[0022]
【発明の実施の形態】式(I)で表される化合物のう
ち、R1 およびR2 が一体となって式(II)を表す化
合物をRP−1551−1、R1 が水素を表し、R2 が
式(III)を表す化合物をRP−1551−2、R1
およびR2 が一体となって式(IV)を表す化合物をR
P−1551−3、R1 およびR2 が一体となって式
(V)を表す化合物をRP−1551−4とそれぞれ称
する。また、これらの化合物をRP−1551類と総称
する。BEST MODE FOR CARRYING OUT THE INVENTION Among the compounds represented by the formula (I), compounds in which R 1 and R 2 are united to represent the formula (II) are RP-1551-1, R 1 represents hydrogen, Compounds in which R 2 represents formula (III) are RP-1551-2, R 1
And R 2 together form a compound of formula (IV)
The compound in which P-1551-3, R 1 and R 2 are united and represents the formula (V) is referred to as RP-1551-4. In addition, these compounds are collectively referred to as RP-1551s.
【0023】RP−1551類は全て、側鎖の三置換オ
レフィンの立体配置に関する2種の幾何異性体(E体お
よびZ体)の平衡混合物である。その平衡は速やかであ
り、両異性体を純粋な形で単離することはできない。同
様の平衡は上述の類似構造を有する化合物イソクロモフ
ィロン類についても報告されている。RP−1551〜
4のいずれの化合物においても通常E体が主成分、Z体
がマイナー成分であるが、両者の相対的比率は生産法、
単離精製法や保存条件によって変化し一定ではない。RP-1551s are all equilibrium mixtures of two geometric isomers (E-form and Z-form) with respect to the configuration of side-chain trisubstituted olefins. The equilibrium is rapid and both isomers cannot be isolated in pure form. Similar equilibria have been reported for compounds isochromophylones having similar structures as described above. RP-1551
In any of the compounds of 4, the E form is usually the main component and the Z form is the minor component.
It varies depending on the isolation and purification method and storage conditions, and is not constant.
【0024】以下にRP−1551類の理化学的性質を
示すが、これらは全て後述の実施例に示す方法により取
得された E体および Z体の混合物サンプルに関するもの
である。なお、13C および 1H-NMR スペクトルに限り、
E 体、Z 体のシグナルを区別して観測、帰属することが
可能であったので、それぞれを区別して記す。化合物R
P−1551類の理化学的性質を以下に示す。The physicochemical properties of RP-1551s are shown below, and all of them relate to the E and Z isomer mixture samples obtained by the methods described in the examples below. In addition, only for 13 C and 1 H-NMR spectra,
Since it was possible to observe and attribute the signals of the E-form and the Z-form separately, they are described separately. Compound R
The physicochemical properties of P-1551s are shown below.
【0025】RP−1551−1の物理化学的データ
(E 体:Z 体=約 3.5:1 ) 性状:黄色粉末 融点:124.0 〜128.0 ℃ 比旋光度:[α]D 25 = -135 °(c=0.12, CH3OH ) 分子式:C25H29O6Cl FAB マススペクトル:m/z 461 (M+H)+ 高分解能FAB マススペクトル:m/z 461.1738 (M+H)+ 紫外部吸収スペクトル:λmax (CH3OH) nm ( ε) 458
(sh 8,700), 430 (22,300), 409 (28,300), 391 (sh 2
4,900), 355 (22,300), 341 (sh 20,400), 251 (18,90
0) 赤外部吸収スペクトル:νmax (KBr) cm-1 3425, 173
4, 1628, 1558, 1522, 1236, 1111, 84313 C-NMR スペクトル(100MHz, CDCl3 ):δ ppm(多重
度) 1) E異性体 189.17(s), 172.44(s), 158.42(s), 147.83(d), 147.02
(d), 142.21(d), 140.83(s), 131.93(s), 116.43(d), 1
15.35(s), 109.78(s), 105.38(d), 102.53(s), 84.12
(s), 73.49(d), 57.21(d), 47.41(d), 44.88(t), 35.05
(d), 30.10(t),24.11(q), 20.59(q), 20.24(q), 12.38
(q), 11.92(q) 2) Z異性体 189.25(s), 172.44(s), 158.15(s), 147.02(d), 145.36
(d), 140.68(s), 133.86(d), 129.92(s), 118.81(d), 1
15.35(s), 110.1(s), 106.06(d), 102.53(s), 84.12
(s), 73.49(d), 57.15(d), 47.47(d), 44.88(t), 34.09
(d), 30.29(t),24.06(q), 20.97(q), 20.59(q), 20.07
(q), 11.97(q)1 H-NMRスペクトル(400MHz, CDCl3 ):δ ppm(積分,
多重度, 結合定数 J(Hz)) 1) E異性体 7.71(1H,s), 7.06(1H,d,15.8), 6.58(1H,s), 6.07(1H,
d,15.8), 5.66(1H,d,10.0), 4.62(1H,m), 3.36(1H,d,9.
0), 2.99(1H,d,9.0), 2.47(1H,m), 2.39(1H,d,14.3),
1.87(1H,dd,14.3,11.5), 1.84(3H,d,1.0), 1.45(1H,m),
1.42(3H,d,6.4), 1.41(3H,s), 1.34(1H,m), 1.01(3H,
d,6.6), 0.86(3H,t,7.4) 2) Z異性体 7.75(1H,s), 7.45(1H,d,15.6), 6.60(1H,s), 6.16(1H,
d,15.6), 5.51(1H,d,10.0), 4.62(1H,m), 3.37(1H,d,9.
0), 3.00(1H,d,9.0), 2.64(1H,m), 2.39(1H,d,14.3),
1.91(3H,d,1.2), 1.87(1H,dd,14.3,11.5), 1.45(1H,m),
1.42(3H,d,6.4), 1.41(3H,s), 1.34(1H,m), 1.01(3H,
d,6.6), 0.86(3H,t,7.4) Physicochemical data of RP-1551-1
(E form: Z form = approx. 3.5: 1) Property: Yellow powder Melting point: 124.0 to 128.0 ° C Specific rotation: [α] D 25 = -135 ° (c = 0.12, CH 3 OH) Molecular formula: C 25 H 29 O 6 Cl FAB Mass spectrum: m / z 461 (M + H) + High resolution FAB mass spectrum: m / z 461.1738 (M + H) + UV absorption spectrum: λ max (CH 3 OH) nm (ε) 458
(sh 8,700), 430 (22,300), 409 (28,300), 391 (sh 2
4,900), 355 (22,300), 341 (sh 20,400), 251 (18,90)
0) Red external absorption spectrum: ν max (KBr) cm -1 3425, 173
4, 1628, 1558, 1522, 1236, 1111, 843 13 C-NMR spectrum (100MHz, CDCl 3 ): δ ppm (multiplicity) 1) E isomer 189.17 (s), 172.44 (s), 158.42 (s) , 147.83 (d), 147.02
(d), 142.21 (d), 140.83 (s), 131.93 (s), 116.43 (d), 1
15.35 (s), 109.78 (s), 105.38 (d), 102.53 (s), 84.12
(s), 73.49 (d), 57.21 (d), 47.41 (d), 44.88 (t), 35.05
(d), 30.10 (t), 24.11 (q), 20.59 (q), 20.24 (q), 12.38
(q), 11.92 (q) 2) Z isomer 189.25 (s), 172.44 (s), 158.15 (s), 147.02 (d), 145.36
(d), 140.68 (s), 133.86 (d), 129.92 (s), 118.81 (d), 1
15.35 (s), 110.1 (s), 106.06 (d), 102.53 (s), 84.12
(s), 73.49 (d), 57.15 (d), 47.47 (d), 44.88 (t), 34.09
(d), 30.29 (t), 24.06 (q), 20.97 (q), 20.59 (q), 20.07
(q), 11.97 (q) 1 H-NMR spectrum (400MHz, CDCl 3 ): δ ppm (integral,
Multiplicity, coupling constant J (Hz)) 1) E isomer 7.71 (1H, s), 7.06 (1H, d, 15.8), 6.58 (1H, s), 6.07 (1H,
d, 15.8), 5.66 (1H, d, 10.0), 4.62 (1H, m), 3.36 (1H, d, 9.
0), 2.99 (1H, d, 9.0), 2.47 (1H, m), 2.39 (1H, d, 14.3),
1.87 (1H, dd, 14.3,11.5), 1.84 (3H, d, 1.0), 1.45 (1H, m),
1.42 (3H, d, 6.4), 1.41 (3H, s), 1.34 (1H, m), 1.01 (3H,
d, 6.6), 0.86 (3H, t, 7.4) 2) Z isomer 7.75 (1H, s), 7.45 (1H, d, 15.6), 6.60 (1H, s), 6.16 (1H,
d, 15.6), 5.51 (1H, d, 10.0), 4.62 (1H, m), 3.37 (1H, d, 9.
0), 3.00 (1H, d, 9.0), 2.64 (1H, m), 2.39 (1H, d, 14.3),
1.91 (3H, d, 1.2), 1.87 (1H, dd, 14.3,11.5), 1.45 (1H, m),
1.42 (3H, d, 6.4), 1.41 (3H, s), 1.34 (1H, m), 1.01 (3H,
d, 6.6), 0.86 (3H, t, 7.4)
【0026】RP−1551−2の物理化学的データ
(E 体:Z 体=約 3.3:1 ) 性状:黄色粉末 融点:54.0〜55.0℃ 比旋光度:[α]D 29= +24.5 °(c=0.50, CH3OH ) 分子式:C24H31O5Cl FAB マススペクトル:m/z 435 (M+H)+ 高分解能FAB マススペクトル:m/z 435.1909 (M+H)+ 紫外部吸収スペクトル:λmax (CH3OH) nm ( ε) 460
(sh 10,400), 432 (sh26,500), 409 (33,100), 391 (s
h 28,600), 356 (25,500), 340 (sh 22,600), 319 (sh
15,600), 250 (22,300) 赤外部吸収スペクトル:νmax (KBr) cm-1 3431, 170
9, 1624, 1558, 1520, 1213, 964, 85013 C-NMR スペクトル(100MHz, CDCl3 ):δ ppm(多重
度) 1) E異性体 209.84(s), 191.45(s), 158.25(s), 147.89(d), 145.30
(d), 142.28(d), 141.58(s), 131.96(s), 119.22(s), 1
16.40(d), 106.57(s), 105.02(d), 74.11(s), 63.82
(d), 51.20(t), 41.64(t), 40.26(d), 35.06(d), 30.12
(t), 26.75(q),22.43(q), 20.26(q), 12.39(q), 11.93
(q) 2) Z異性体 209.87(s), 191.45(s), 157.97(s), 145.41(d), 145.34
(d), 141.43(s), 133.86(d), 129.89(s), 118.83(d), 1
10.47(s), 106.88(s), 105.71(d), 74.11(s), 63.82
(d), 51.17(t), 41.58(t), 40.26(d), 34.11(d), 30.30
(t), 26.73(q),22.43(q), 20.98(q), 20.10(q), 11.99
(q)1 H-NMRスペクトル(400MHz, CDCl3 ):δ ppm(積分,
多重度, 結合定数 J(Hz)) 1) E異性体 7.41(1H,s), 7.03(1H,d,15.6), 6.50(1H,s), 6.04(1H,
d,15.6), 5.65(1H,d,9.5), 4.17(1H,m), 3.43(1H,dd,9.
5,3.5), 3.09(1H,dd,18.1,3.5), 2.48(1H,m),2.46(1H,
m), 2.45(1H,m), 2.34(1H,dd,18.1,9.5), 1.82(3H,d,1.
2), 1.42(1H,m), 1.31(3H,s), 1.26(1H,m), 1.15(3H,d,
6.4), 1.00(3H,d,6.5), 0.85(3H,t,7.5) 2) Z異性体 7.45(1H,s), 7.42(1H,d,15.6), 6.52(1H,s), 6.13(1H,
d,15.6), 5.50(1H,d,10.7), 4.17(1H,m), 3.44(1H,dd,
9.5,3.4), 3.10(1H,dd,18.1,3.4), 2.63(1H,m), 2.48(1
H,m), 2.46(1H,m), 2.35(1H,dd,18.1,9.5), 1.90(3H,d,
1.2), 1.42(1H,m), 1.31(3H,s), 1.26(1H,m), 1.16(3H,
d,6.3), 1.01(3H,d,6.8), 0.86(3H,t,7.5) Physicochemical data of RP-1551-2
(E form: Z form = approx. 3.3: 1) Property: Yellow powder Melting point: 54.0-55.0 ° C Specific rotation: [α] D 29 = + 24.5 ° (c = 0.50, CH 3 OH) Molecular formula: C 24 H 31 O 5 Cl FAB Mass spectrum: m / z 435 (M + H) + High resolution FAB mass spectrum: m / z 435.1909 (M + H) + UV absorption spectrum: λ max (CH 3 OH) nm (ε) 460
(sh 10,400), 432 (sh26,500), 409 (33,100), 391 (s
h 28,600), 356 (25,500), 340 (sh 22,600), 319 (sh
15,600), 250 (22,300) Red External absorption spectrum: ν max (KBr) cm -1 3431, 170
9, 1624, 1558, 1520, 1213, 964, 850 13 C-NMR spectrum (100MHz, CDCl 3 ): δ ppm (multiplicity) 1) E isomer 209.84 (s), 191.45 (s), 158.25 (s) , 147.89 (d), 145.30
(d), 142.28 (d), 141.58 (s), 131.96 (s), 119.22 (s), 1
16.40 (d), 106.57 (s), 105.02 (d), 74.11 (s), 63.82
(d), 51.20 (t), 41.64 (t), 40.26 (d), 35.06 (d), 30.12
(t), 26.75 (q), 22.43 (q), 20.26 (q), 12.39 (q), 11.93
(q) 2) Z isomer 209.87 (s), 191.45 (s), 157.97 (s), 145.41 (d), 145.34
(d), 141.43 (s), 133.86 (d), 129.89 (s), 118.83 (d), 1
10.47 (s), 106.88 (s), 105.71 (d), 74.11 (s), 63.82
(d), 51.17 (t), 41.58 (t), 40.26 (d), 34.11 (d), 30.30
(t), 26.73 (q), 22.43 (q), 20.98 (q), 20.10 (q), 11.99
(q) 1 H-NMR spectrum (400MHz, CDCl 3 ): δ ppm (integral,
Multiplicity, coupling constant J (Hz)) 1) E isomer 7.41 (1H, s), 7.03 (1H, d, 15.6), 6.50 (1H, s), 6.04 (1H,
d, 15.6), 5.65 (1H, d, 9.5), 4.17 (1H, m), 3.43 (1H, dd, 9.
5,3.5), 3.09 (1H, dd, 18.1,3.5), 2.48 (1H, m), 2.46 (1H,
m), 2.45 (1H, m), 2.34 (1H, dd, 18.1,9.5), 1.82 (3H, d, 1.
2), 1.42 (1H, m), 1.31 (3H, s), 1.26 (1H, m), 1.15 (3H, d,
6.4), 1.00 (3H, d, 6.5), 0.85 (3H, t, 7.5) 2) Z isomer 7.45 (1H, s), 7.42 (1H, d, 15.6), 6.52 (1H, s), 6.13 ( 1H,
d, 15.6), 5.50 (1H, d, 10.7), 4.17 (1H, m), 3.44 (1H, dd,
9.5,3.4), 3.10 (1H, dd, 18.1,3.4), 2.63 (1H, m), 2.48 (1
H, m), 2.46 (1H, m), 2.35 (1H, dd, 18.1,9.5), 1.90 (3H, d,
1.2), 1.42 (1H, m), 1.31 (3H, s), 1.26 (1H, m), 1.16 (3H,
d, 6.3), 1.01 (3H, d, 6.8), 0.86 (3H, t, 7.5)
【0027】RP−1551−3の物理化学的データ
(E 体:Z 体=約 2.8:1 ) 性状:黄色粉末 融点:91.0〜93.0℃ 比旋光度:[α]D 30 = -335 °(c=0.066, CH3OH) 分子式:C25H27O5Cl FAB マススペクトル:m/z 443 (M+H)+ 高分解能FAB マススペクトル:m/z 443.1612 (M+H)+ 紫外部吸収スペクトル:λmax (CH3OH) nm ( ε) 462
(sh 11,100), 433 (27,100), 412 (31,800), 391 (sh
25,800), 360 (21,700), 342 (sh 19,400), 241(22,30
0) 赤外部吸収スペクトル:νmax (KBr) cm-1 3444, 178
4, 1693, 1668, 1631,1558, 1520, 1431, 1242, 1090,
962, 84713 C-NMR スペクトル(100MHz, CDCl3 ):δ ppm(多重
度) 1) E異性体 90.06(s), 184.31(s), 168.38(s), 158.79(s), 148.44
(d), 147.89(d), 146.22(d), 142.78(d), 140.65(s), 1
31.94(s), 130.44(d), 116.14(d), 113.51(s), 109.31
(s), 105.11(d), 83.58(s), 54.56(d), 42.71(d), 35.1
0(d), 30.09(t), 23.38(q), 20.22(q), 18.73(q), 12.3
9(q), 11.92(q) 2) Z異性体 190.01(s), 184.31(s), 168.35(s), 158.51(s), 147.89
(d), 146.22(d), 145.89(d), 140.51(s), 134.34(d), 1
30.40(t), 129.89(s), 118.54(d), 113.51(s), 109.60
(s), 105.79(d), 83.55(s), 54.56(d), 42.71(d), 35.1
0(d), 30.27(t), 23.38(q), 20.95(q), 20.05(q), 18.7
3(q), 11.99(q)1 H-NMRスペクトル(400MHz, CDCl3 ):δ ppm(積分,
多重度, 結合定数 J(Hz)) 1) E異性体 7.41(1H,s), 7.03(1H,d,15.6), 7.01(1H,dq,15.7,6.9),
6.55(1H,s), 6.43(1H,dq,15.7,1.7), 6.05(1H,d,15.
6), 5.66(1H,d,9.8), 4.01(1H,s), 4.00(1H,s), 2.47(1
H,m), 1.97(3H,dd,6.9,1.7), 1.83(3H,d,1.2), 1.63(3
H,s), 1.42(1H,m), 1.3(1H,m), 1.01(3H,d,6.6), 0.86
(3H,t,7.5) 2) Z異性体 7.46(1H,s), 7.43(1H,d,15.6), 7.01(1H,dq,15.7,6.9),
6.52(1H,s), 6.43(1H,dq,15.7,1.7), 6.14(1H,d,15.
6), 5.52(1H,d,10.0), 4.01(1H,s), 4.01(1H,s), 2.62
(1H,m), 1.97(3H,dd,6.9,1.7), 1.90(3H,d,1.2), 1.63
(3H,s), 1.42(1H,m), 1.30(1H,m), 1.00(3H,d,6.6), 0.
85(3H,t,7.5) Physicochemical data of RP-1551-3
(E form: Z form = about 2.8: 1) Property: Yellow powder Melting point: 91.0-93.0 ℃ Specific rotation: [α] D 30 = -335 ° (c = 0.066, CH 3 OH) Molecular formula: C 25 H 27 O 5 Cl FAB Mass spectrum: m / z 443 (M + H) + High resolution FAB mass spectrum: m / z 443.1612 (M + H) + UV absorption spectrum: λ max (CH 3 OH) nm (ε) 462
(sh 11,100), 433 (27,100), 412 (31,800), 391 (sh
25,800), 360 (21,700), 342 (sh 19,400), 241 (22,30
0) Red external absorption spectrum: ν max (KBr) cm -1 3444, 178
4, 1693, 1668, 1631, 1558, 1520, 1431, 1242, 1090,
962, 847 13 C-NMR spectrum (100MHz, CDCl 3 ): δ ppm (multiplicity) 1) E isomer 90.06 (s), 184.31 (s), 168.38 (s), 158.79 (s), 148.44
(d), 147.89 (d), 146.22 (d), 142.78 (d), 140.65 (s), 1
31.94 (s), 130.44 (d), 116.14 (d), 113.51 (s), 109.31
(s), 105.11 (d), 83.58 (s), 54.56 (d), 42.71 (d), 35.1
0 (d), 30.09 (t), 23.38 (q), 20.22 (q), 18.73 (q), 12.3
9 (q), 11.92 (q) 2) Z isomer 190.01 (s), 184.31 (s), 168.35 (s), 158.51 (s), 147.89
(d), 146.22 (d), 145.89 (d), 140.51 (s), 134.34 (d), 1
30.40 (t), 129.89 (s), 118.54 (d), 113.51 (s), 109.60
(s), 105.79 (d), 83.55 (s), 54.56 (d), 42.71 (d), 35.1
0 (d), 30.27 (t), 23.38 (q), 20.95 (q), 20.05 (q), 18.7
3 (q), 11.99 (q) 1 H-NMR spectrum (400MHz, CDCl 3 ): δ ppm (integral,
Multiplicity, coupling constant J (Hz)) 1) E isomer 7.41 (1H, s), 7.03 (1H, d, 15.6), 7.01 (1H, dq, 15.7,6.9),
6.55 (1H, s), 6.43 (1H, dq, 15.7,1.7), 6.05 (1H, d, 15.
6), 5.66 (1H, d, 9.8), 4.01 (1H, s), 4.00 (1H, s), 2.47 (1
H, m), 1.97 (3H, dd, 6.9,1.7), 1.83 (3H, d, 1.2), 1.63 (3
H, s), 1.42 (1H, m), 1.3 (1H, m), 1.01 (3H, d, 6.6), 0.86
(3H, t, 7.5) 2) Z isomer 7.46 (1H, s), 7.43 (1H, d, 15.6), 7.01 (1H, dq, 15.7,6.9),
6.52 (1H, s), 6.43 (1H, dq, 15.7,1.7), 6.14 (1H, d, 15.
6), 5.52 (1H, d, 10.0), 4.01 (1H, s), 4.01 (1H, s), 2.62
(1H, m), 1.97 (3H, dd, 6.9,1.7), 1.90 (3H, d, 1.2), 1.63
(3H, s), 1.42 (1H, m), 1.30 (1H, m), 1.00 (3H, d, 6.6), 0.
85 (3H, t, 7.5)
【0028】RP−1551−4の物理化学的データ
(E 体:Z 体=約 2.4:1 ) 性状:黄色粉末 融点:82.0〜84.0℃ 比旋光度:[α]D 24 = -306 °(c=0.20, CH3OH ) 分子式:C25H29O6Cl FAB マススペクトル:m/z 461 (M+H)+ 高分解能FAB マススペクトル:m/z 461.1717 (M+H)+ 紫外部吸収スペクトル:λmax (CH3OH) nm ( ε) 461
(sh 26,100), 433 (59,300), 413 (70,700), 392 (sh
57,900), 359 (48,700), 342 (sh 42,000), 253(28,00
0) 赤外部吸収スペクトル:νmax (KBr) cm-1 3444, 177
8, 1716, 1626, 1556, 1516, 1433, 1244, 1093, 849,
68113 C-NMR スペクトル(100MHz, CDCl3 ):δ ppm(多重
度) 1) E異性体 202.19(s), 183.97(s), 168.22(s), 158.79(s), 148.58
(d), 146.45(d), 142.93(d), 140.66(s), 131.95(s), 1
16.10(d), 113.28(s), 109.30(s), 105.14(d), 83.62
(s), 64.13(d), 56.95(d), 50.81(t), 42.46(d), 35.13
(d), 30.11(t),23.40(q), 22.96(q), 20.23(q), 12.39
(q), 11.93(q) 2) Z異性体 202.19(s), 184.07(s), 168.20(s), 158.51(s), 146.48
(d), 146.01(d), 140.51(s), 134.47(d), 129.89(s), 1
18.51(d), 113.28(s), 109.58(s), 105.82(d), 83.62
(s), 64.13(d), 56.91(d), 50.76(t), 42.46(d), 34.20
(d), 30.28(t),23.40(q), 22.96(q), 20.97(q), 20.07
(q), 12.00(q)1 H-NMRスペクトル(400MHz, CDCl3 ):δ ppm(積分,
多重度, 結合定数 J(Hz)) 1) E異性体 7.44(1H,s), 7.05(1H,d,15.7), 6.55(1H,s), 6.06(1H,
d,15.7), 5.68(1H,d,9.8), 4.28(1H,m), 3.888(2H,s),
3.115(1H,dd,17.4,8.6), 2.80(1H,dd,17.4,3.2), 2.47
(1H,m), 1.83(3H,d,1.0), 1.62(3H,s), 1.42(1H,m), 1.
30(1H,m), 1.24(3H,d,6.1), 1.01(3H,d,6.6), 0.855(3
H,t,7.5) 2) Z異性体 7.480(1H,s), 7.45(1H,d,15.6), 6.570(1H,s), 6.15(1
H,d,15.6), 5.53(1H,d,9.8), 4.28(1H,m), 3.892(2H,
s), 3.121(1H,dd,17.4,8.6), 2.81(1H,dd,17.4,3.2),
2.62(1H,m), 1.91(3H,d,1.2), 1.62(3H,s), 1.42(1H,
m), 1.30(1H,m), 1.25(3H,d,6.4), 1.01(3H,d,6.6), 0.
860(3H,t,7.5) 上記化合物のうち、RP−1551−1はTL−3およ
びTL−4と同一の平面構造を有するが、8 位に対する
2' 位および5'位の相対立体配置に関し両者は異なって
いる。TL−3およびTL−4に関しては 7位メチル基
と 8位水素、8位水素と 2' 位水素、2'位水素と 5' 位
水素がいずれも synの配置である。これに対しRP−1
551−1では7 位メチル基と 8位水素、および 2' 位
水素と 5' 位水素はいずれも同様に synの配置である
が、8 位水素と 2' 位水素は antiの配置である。この
ことは、NMR スペクトルにおけるNOESY 実験および差 N
OE実験で、7 位メチル基と 8位水素、および2'位水素と
5' 位水素の間にはそれぞれNOEが観測されるのに対
し、8 位水素と2'位水素の間にはNOE が観測されないこ
とから決定された。従って、RP−1551−1がTL
−3またはTL−4と異なる物質であることは明らかで
ある。 Physicochemical data of RP-1551-4
(E form: Z form = about 2.4: 1) Property: Yellow powder Melting point: 82.0 ~ 84.0 ° C Specific rotation: [α] D 24 = -306 ° (c = 0.20, CH 3 OH) Molecular formula: C 25 H 29 O 6 Cl FAB Mass spectrum: m / z 461 (M + H) + High resolution FAB mass spectrum: m / z 461.1717 (M + H) + UV absorption spectrum: λ max (CH 3 OH) nm (ε) 461
(sh 26,100), 433 (59,300), 413 (70,700), 392 (sh
57,900), 359 (48,700), 342 (sh 42,000), 253 (28,00
0) Red external absorption spectrum: ν max (KBr) cm -1 3444, 177
8, 1716, 1626, 1556, 1516, 1433, 1244, 1093, 849,
681 13 C-NMR spectrum (100MHz, CDCl 3 ): δ ppm (multiplicity) 1) E isomer 202.19 (s), 183.97 (s), 168.22 (s), 158.79 (s), 148.58
(d), 146.45 (d), 142.93 (d), 140.66 (s), 131.95 (s), 1
16.10 (d), 113.28 (s), 109.30 (s), 105.14 (d), 83.62
(s), 64.13 (d), 56.95 (d), 50.81 (t), 42.46 (d), 35.13
(d), 30.11 (t), 23.40 (q), 22.96 (q), 20.23 (q), 12.39
(q), 11.93 (q) 2) Z isomer 202.19 (s), 184.07 (s), 168.20 (s), 158.51 (s), 146.48
(d), 146.01 (d), 140.51 (s), 134.47 (d), 129.89 (s), 1
18.51 (d), 113.28 (s), 109.58 (s), 105.82 (d), 83.62
(s), 64.13 (d), 56.91 (d), 50.76 (t), 42.46 (d), 34.20
(d), 30.28 (t), 23.40 (q), 22.96 (q), 20.97 (q), 20.07
(q), 12.00 (q) 1 H-NMR spectrum (400MHz, CDCl 3 ): δ ppm (integral,
Multiplicity, coupling constant J (Hz)) 1) E isomer 7.44 (1H, s), 7.05 (1H, d, 15.7), 6.55 (1H, s), 6.06 (1H,
d, 15.7), 5.68 (1H, d, 9.8), 4.28 (1H, m), 3.888 (2H, s),
3.115 (1H, dd, 17.4,8.6), 2.80 (1H, dd, 17.4,3.2), 2.47
(1H, m), 1.83 (3H, d, 1.0), 1.62 (3H, s), 1.42 (1H, m), 1.
30 (1H, m), 1.24 (3H, d, 6.1), 1.01 (3H, d, 6.6), 0.855 (3
H, t, 7.5) 2) Z isomer 7.480 (1H, s), 7.45 (1H, d, 15.6), 6.570 (1H, s), 6.15 (1
H, d, 15.6), 5.53 (1H, d, 9.8), 4.28 (1H, m), 3.892 (2H,
s), 3.121 (1H, dd, 17.4,8.6), 2.81 (1H, dd, 17.4,3.2),
2.62 (1H, m), 1.91 (3H, d, 1.2), 1.62 (3H, s), 1.42 (1H,
m), 1.30 (1H, m), 1.25 (3H, d, 6.4), 1.01 (3H, d, 6.6), 0.
860 (3H, t, 7.5) Of the above compounds, RP-1551-1 has the same planar structure as TL-3 and TL-4, but for the 8-position
Both differ in the relative configuration at the 2'and 5'positions. Regarding TL-3 and TL-4, the 7-position methyl group and 8-position hydrogen, the 8-position hydrogen and 2'-position hydrogen, and the 2'-position hydrogen and 5'-position hydrogen are all in syn configuration. On the other hand, RP-1
In 551-1, the 7-position methyl group and 8-position hydrogen, and the 2'-position hydrogen and the 5'-position hydrogen all have the syn configuration, but the 8-position hydrogen and the 2'-position hydrogen have the anti configuration. This is due to the NOESY experiment and the difference N in the NMR spectrum.
In the OE experiment, the 7-position methyl group and the 8-position hydrogen, and the 2'-position hydrogen
It was determined that NOE was observed between the 5'-position hydrogen and NOE was not observed between the 8-position hydrogen and the 2'-position hydrogen. Therefore, RP-1551-1 is TL
-3 or TL-4 is clearly a different substance.
【0029】以上のデータより化合物RP−1551類
は新規化合物であることが判明した。各種細菌に対する
化合物RP−1551類の生物活性を以下に示す。From the above data, it was found that the compounds RP-1551s are novel compounds. The biological activity of compounds RP-1551s against various bacteria is shown below.
【0030】試験例1 各種細菌に対する抗菌活性 抗菌活性は、バクトトリプトン(Difco 社製)3g/L、肉
エキス3g/L、酵母エキス 1g/L 、グルコース1g/L、寒天
16g/L の組成からなる培地(pH7.0)を用いて寒天希釈法
により測定した。各種細菌に対する最小生育阻止濃度(M
IC) を第1表に示す。Test Example 1 Antibacterial activity against various bacteria Antibacterial activity was 3 g / L bactotryptone (manufactured by Difco), 3 g / L meat extract, 1 g / L yeast extract, 1 g / L glucose, agar
It was measured by an agar dilution method using a medium (pH 7.0) having a composition of 16 g / L. Minimum growth inhibitory concentration (M
IC) is shown in Table 1.
【0031】[0031]
【表1】 [Table 1]
【0032】化合物RP−1551類は、ペニシリウム
属に属し、化合物RP−1551類生産能を有する微生
物を培地に培養し、培養物中に化合物RP−1551類
を生成蓄積させ、該培養物から化合物RP−1551類
を採取することによって製造される。化合物RP−15
51類生産能を有する微生物としては、ペニシリウム属
に属し、化合物RP−1551類生産能を有する菌株で
あればいずれの菌株でも用いることができる。また、こ
れらの菌株を人工的変異方法、たとえば紫外線照射、X
線照射、変異誘発剤処理などによって変異させた変異株
あるいは自然的に変異した変異株などでも化合物RP−
1551類生産能を有していれば本発明に用いることが
できる。The compound RP-1551s are compounds belonging to the genus Penicillium and having the ability to produce the compound RP-1551s are cultured in a medium to produce and accumulate the compounds RP-1551s in the culture. It is produced by collecting RP-1551s. Compound RP-15
As the microorganism capable of producing 51s, any strain can be used as long as it is a strain belonging to the genus Penicillium and capable of producing the compound RP-1551s. In addition, these strains can be artificially mutagenized, for example, by ultraviolet irradiation, X
The compound RP-can also be a mutant strain mutated by irradiation with radiation, treatment with a mutagen or the like, or a mutant strain naturally mutated.
It can be used in the present invention as long as it has the ability to produce 1551s.
【0033】具体的に好適な例としては、ペニシリウム
・エスピー( Penicillium sp.)SPC−21609株が
あげられる。ペニシリウム・エスピー( Penicillium s
p.)SPC−21609株の菌学的性質は次のとおりで
ある。 肉眼的観察 麦芽エキス寒天培地を用いて、24℃で培養したとき、
集落の直径は培養7日目で23〜24mm、培養14日
目で約43mmに達する。培養7日目の集落中央部はオ
レンジ色で、周囲は白色を呈し、その裏面は、暗オレン
ジ色を呈し、黄色の可溶性色素を培地中に出す。A particularly preferred example is Penicillium sp. SPC-21609 strain. Penicillium s
p.) SPC-21609 strain has the following mycological properties. Macroscopic observation When cultured at 24 ° C using malt extract agar medium,
The diameter of the colony reaches 23 to 24 mm on the 7th day of culture and reaches about 43 mm on the 14th day of culture. On the 7th day of culture, the central part of the colony is orange, the periphery is white, the back side is dark orange, and yellow soluble pigment is put out in the medium.
【0034】バレイショ・ブドウ糖寒天培地を用いて、
25℃で培養したとき、集落の直径は培養7日目で約2
4mm、培養14日目で約40mmに達する。培養7日
目の集落の様子は麦芽エキス寒天培地上と同様である。
本菌株の至適生育温度は15〜36℃であり、28℃前
後で最も良好に生育する。生育し得るpHは2〜8で、至
適生育pHは5〜6である。 光学顕微鏡的観察 麦芽エキス寒天培地上で培養したときの本菌株の光学顕
微鏡による観察結果は以下のとおりである。Using potato-glucose agar medium,
When cultivated at 25 ° C, the diameter of the colony was about 2 on the 7th day of culturing.
4 mm, reaching about 40 mm on day 14 of culture. The appearance of the colony on the 7th day of culture is the same as that on the malt extract agar medium.
The optimum growth temperature of this strain is 15 to 36 ° C, and it grows best at around 28 ° C. The pH that can grow is 2 to 8, and the optimum growth pH is 5 to 6. Observation with an optical microscope The following are the results of observation with an optical microscope of this strain when cultured on a malt extract agar medium.
【0035】菌糸は隔壁を有し、無色から黄褐色あるい
は赤褐色を呈し、平滑でよく分岐する。分生子柄は束状
になることはなく、菌糸から単生して立ち上がる。分生
子柄は、平滑、無色から淡黄褐色を呈し、長さ約200
μmに達し、幅約3μmである。分生子柄の先端に3〜
5本のメトレが形成され、そのメトレの先端に3〜5個
のフィアライドが形成される。また、分生子柄とメトレ
の間にラミーを形成する場合もある。メトレは円筒形
で、長さ6〜14μm、幅1.5〜3.5μmを呈す
る。フィアライドはトックリ形を呈し、長さ9〜12μ
m、幅は最も広い部位において2〜3.5μmを呈す
る。ラミーは円筒形で、長さ約20μm、幅約2μmを
呈する。分生子の個体発生様式は内生出芽型のフィアロ
型であり、分生子はフィアライド先端より形成し、連鎖
状となる。フィアロ型分生子は、単細胞、無色、楕円形
あるいは亜球形で、長さ2〜3μm、幅1.5〜2μ
m、表面は平滑を呈する。本菌株は、上述したアナモル
フ(anamorph)のみ観察され、テレオモルフ(teleomor
ph)は観察されない。The hypha has a partition wall and exhibits colorless to yellowish brown or reddish brown, and is smooth and well branched. The conidia peduncle does not form a bundle, but stands alone from the hyphae. Conidia peduncle is smooth, colorless to pale yellowish brown, and has a length of about 200.
The width is about 3 μm. 3 to the tip of the conidia handle
Five metres are formed, and 3-5 phialides are formed at the tip of the metres. In addition, a ramie may be formed between the conidia peduncle and the metre. The metre is cylindrical and has a length of 6 to 14 μm and a width of 1.5 to 3.5 μm. Fear ride has a tongue-like shape and a length of 9-12μ
m, the width is 2 to 3.5 μm in the widest part. The ramie is cylindrical and has a length of about 20 μm and a width of about 2 μm. The ontogeny of conidia is of the endophytic type, which is the fiaro type. Conidia are formed from the tip of the phialide and form a chain. Phialoconidia are unicellular, colorless, elliptical or subspherical, with a length of 2-3 μm and a width of 1.5-2 μm.
m, the surface is smooth. In this strain, only the above-mentioned anamorph was observed, and there was a teleomorph.
ph) is not observed.
【0036】以上の菌学的性質から、本菌の分類学上の
位置を「ザ・ジェネラ・オブ・ファンジャイ・スポルレ
イティング・イン・ピュア・カルチャー第2版(The Ge
neraof Fungi Sporulating in Pure Culture, 2nd ed.
Cramer, Vaduz, J. A. vonArx, 1974 )」に従って検索
した結果、本菌株は、ペニシリウム (Penicillium) 属
に属すると同定された。From the above-mentioned mycological properties, the taxonomic position of this bacterium is determined as "The Genera of Fanjayi Poring in Pure Culture 2nd Edition (The Ge
neraof Fungi Sporulating in Pure Culture, 2nd ed.
Cramer, Vaduz, JA vonArx, 1974) ”, the strain was identified as belonging to the genus Penicillium .
【0037】本菌株は、ペニシリウム・スピーシーズ
(Penicillium sp.)SPC−21609と命名され、ブ
ダペスト条約に基づいて平成6年8月4日付けで、工業
技術院生命工学工業技術研究所にFERM BP-4768として寄
託してある。本発明の化合物RP−1551−1生産菌
の培養に際しては、糸状菌の培養に用いられる通常の培
養方法が適用される。用いられる培地は、菌の資化し得
る炭素源、窒素源、無機物などを程よく含有する培地で
あれば天然培地、合成培地いずれでも用いられる。This strain is Penicillium species
It is named ( Penicillium sp.) SPC-21609, and has been deposited as FERM BP-4768 at the Institute of Biotechnology, Institute of Industrial Science, Agency of Industrial Science and Technology, on August 4, 1994, based on the Budapest Treaty. In culturing the compound RP-1551-1 producing bacterium of the present invention, a usual culturing method used for culturing a filamentous fungus is applied. The medium to be used may be either a natural medium or a synthetic medium as long as it contains a carbon source, a nitrogen source, an inorganic substance and the like that can be assimilated by the bacterium.
【0038】炭素源としては、グルコース、シュークロ
ース、澱粉、デキストリン、マンノース、マルトース、
糖蜜、マッシュポテトの素などの炭水化物、クエン酸、
リンゴ酸、酢酸、フマール酸などの有機酸、メタノー
ル、エタノールなどのアルコール、メタン、エタン、プ
ロパン、n−パラフィンなどの炭化水素、グルタミン酸
などのアミノ酸あるいはグリセロールなどが用いられ
る。As carbon sources, glucose, sucrose, starch, dextrin, mannose, maltose,
Molasses, mashed potatoes and other carbohydrates, citric acid,
Organic acids such as malic acid, acetic acid and fumaric acid, alcohols such as methanol and ethanol, hydrocarbons such as methane, ethane, propane and n-paraffin, amino acids such as glutamic acid and glycerol are used.
【0039】窒素源としては、塩化アンモニウム、硫酸
アンモニウム、硝酸アンモニウム、リン酸アンモニウム
などのアンモニウム塩、アスパラギン酸、グルタミン、
シスチン、アラニンなどのアミノ酸、尿素、ペプトン、
肉エキス、酵母エキス、乾燥酵母、麦芽エキス、コーン
・スチープ・リカー、大豆粉、ソルブル・ベジタブル・
プロテイン、綿実粕、大豆カゼイン、カザミノ酸、ファ
ーマメディア、野菜ジュースなどが用いられる。As the nitrogen source, ammonium salts such as ammonium chloride, ammonium sulfate, ammonium nitrate and ammonium phosphate, aspartic acid, glutamine,
Amino acids such as cystine and alanine, urea, peptone,
Meat extract, yeast extract, dry yeast, malt extract, corn steep liquor, soybean powder, soluble vegetable
Protein, cottonseed meal, soybean casein, casamino acid, pharmaceutical media, vegetable juice, etc. are used.
【0040】無機物としては、リン酸一水素カリウム、
リン酸二水素カリウム、リン酸二水素ナトリウム、リン
酸マグネシウム、硫酸マグネシウム、硫酸第一鉄、硫酸
マンガン、硫酸銅、硫酸コバルト、硫酸亜鉛、パントテ
ン酸カルシウム、モリブデン酸アンモニウム、硫酸アル
ミニウムカリウム、炭酸バリウム、炭酸カルシウム、塩
化コバルト、食塩などが用いられる。As the inorganic substance, potassium monohydrogen phosphate,
Potassium dihydrogen phosphate, sodium dihydrogen phosphate, magnesium phosphate, magnesium sulfate, ferrous sulfate, manganese sulfate, copper sulfate, cobalt sulfate, zinc sulfate, calcium pantothenate, ammonium molybdate, potassium aluminum sulfate, barium carbonate. , Calcium carbonate, cobalt chloride, salt and the like are used.
【0041】その他必要に応じて、培地にビタミン、サ
イアミンなど菌体の増殖あるいは化合物RP−1551
類の生産を促進する物質を加える。また、用いる微生物
が特定の物質を要求する場合は、該物質を加える。培養
は振盪培養法、通気撹拌培養法などにより、15〜35
℃の温度で、中性付近のpHで行われる。通常3〜15日
の培養によって、化合物RP−1551類の蓄積は最大
に達する。In addition, if necessary, the growth of bacterial cells such as vitamins and thiamine or the compound RP-1551 is added to the medium.
Add substances that promote the production of varieties. When the microorganism used requires a specific substance, the substance is added. Culture is performed by shaking culture, aeration stirring culture, or the like for 15 to 35
It is carried out at a temperature of ° C and a pH near neutral. Usually, after 3 to 15 days of culture, the maximum accumulation of compound RP-1551s is reached.
【0042】培養液中に蓄積した化合物RP−1551
類を培養液から単離採取するに際しては、培養液から生
理活性物質を採取する通常の方法が適用される。すなわ
ち、アセトン、メタノールなどの有機溶媒による菌体成
分の抽出、ろ過、遠心分離などによる菌体除去、吸着樹
脂、シリカゲル、シラナイズドシリカゲル、逆相シリカ
ゲル、酸化アルミニウム、セルロース、ケイ藻土、ケイ
酸マグネシウム、ゲルろ過剤、イオン交換樹脂などを用
いるカラムクロマトグラフィーもしくは薄層クロマトグ
ラフィーによる活性物質の吸脱着処理もしくは、適当な
溶媒系による分配などによって化合物RP−1551類
は単離される。Compound RP-1551 accumulated in the culture medium
When isolating and collecting the species from the culture medium, a usual method for collecting a physiologically active substance from the culture medium is applied. That is, extraction of cell components with an organic solvent such as acetone or methanol, filtration, cell removal by centrifugation, adsorption resin, silica gel, silanized silica gel, reverse phase silica gel, aluminum oxide, cellulose, diatomaceous earth, silicic acid. Compounds RP-1551s are isolated by adsorption / desorption treatment of the active substance by column chromatography or thin layer chromatography using magnesium, gel filtration agent, ion exchange resin or the like, or partitioning with an appropriate solvent system.
【0043】上記精製工程中の化合物RP−1551類
の検出は、蛍光剤入りシリカゲル(キーゼルゲルF254
、メルク社製)を用いた薄層クロマトグラフィーに付
し、ヨウ素反応または253.7nmの紫外線照射法によ
り行うことができる。以下に本発明の実施例を示す。The compounds RP-1551s in the above purification step were detected by a fluorescent agent-containing silica gel (Kieselgel F254).
, Manufactured by Merck & Co., Inc.) and subjected to iodine reaction or 253.7 nm ultraviolet irradiation method. Examples of the present invention will be shown below.
【0044】[0044]
【0045】実施例1 種菌として、ペニシリウム・エスピー(Penicillium s
p.)SPC−21609株(FERM BP-4768)を用い、第一
種培地としてマッシュポテトの素(雪印乳業社製)3g
/dL、グルコース10g /dL、酵母エキス0.5g /dL
(pH6.5)の組成からなる培地を用いた。種菌一白
金耳を太型試験管に入れた上記第一種培地10mLに植菌
し、25℃で5日間振盪培養した(第一種培養)。[0045] As Example 1 seed, Penicillium sp. (Penicillium s
p.) SPC-21609 strain (FERM BP-4768) was used, and 3 g of mashed potato broth (Snow Brand Milk Products Co., Ltd.) was used as the first type medium.
/ DL, glucose 10g / dL, yeast extract 0.5g / dL
A medium having a composition of (pH 6.5) was used. The inoculum 1 platinum loop was inoculated into 10 mL of the above-mentioned type 1 medium contained in a thick test tube, and cultured with shaking at 25 ° C for 5 days (type 1 culture).
【0046】第一種培養により得られた培養液(第一種
培養液)10mLを300mL三角フラスコに入った50mL
の第二種培地に植菌した。第二種培地の組成は第一種培
地の組成と同じである。第二種培養は28℃で2日間行
った。得られた第二種培養液10mLを300mL三角フラ
スコに入った50mLの主発酵培地に植菌した。主発酵培
地として、シュークロース3g /dL、可溶性澱粉2g/d
L、乾燥酵母(アサヒビール社製)0.5g /dL、麦芽
エキス1g /dL、コーン・スチープ・リカー0.5g /
dL、野菜ジュース(Campbell社製)20mL/dL、炭酸カ
ルシウム1.5g /dL(pH6.5)の組成からなる培地
を用いた。主発酵培養は25℃で7日間振盪培養するこ
とにより行った。50 mL of a culture solution (first culture solution) obtained by the first culture was placed in a 300 mL Erlenmeyer flask.
Was inoculated into the second type medium. The composition of the second type medium is the same as that of the first type medium. The second seed culture was performed at 28 ° C. for 2 days. 10 mL of the obtained second seed culture was inoculated into 50 mL of the main fermentation medium contained in a 300 mL Erlenmeyer flask. Main fermentation medium: sucrose 3g / dL, soluble starch 2g / d
L, dry yeast (Asahi Breweries) 0.5 g / dL, malt extract 1 g / dL, corn steep liquor 0.5 g /
A medium having a composition of dL, vegetable juice (Campbell) 20 mL / dL, and calcium carbonate 1.5 g / dL (pH 6.5) was used. The main fermentation culture was performed by shaking culture at 25 ° C. for 7 days.
【0047】得られた発酵培養液800mLをろ過し、分
別した菌体に800mLのメタノールを加え撹拌後ろ過し
た。ろ液に800mLの脱イオン水を添加し、脱イオン水
を用いて充填した80mLのダイヤイオンHP−20ss
(三菱化成社製:登録商標)カラムに通塔した。カラム
を50%メタノール水溶液300mLで洗浄後、300mL
のメタノール/アセトン混合溶媒(7:3)で溶出し
た。溶出液を減圧下で濃縮して、794mgの黄色油状物
質を得た。この物質を少量の10%の2−ブタノンを含
むクロロホルム溶液に溶解し、同じ組成の溶媒を用いて
充填した100mLのシリカゲル(メルク社製、Art.773
4)カラムの上端にのせ、同じ組成の溶媒を用いて活性
物質を溶出した。溶出液を20mLずつ分取すると、化合
物RP−1551−1は画分番号16〜32に溶出され
た。これらの画分を集めた後、減圧下で濃縮乾固して1
34mgの黄色固体を得た。この物質を少量の70%アセ
トニトリル水溶液に溶解し、同じ組成の溶媒を用いて充
填した150mLの逆相シリカゲル(YMC社製、ODS
−AQS50)カラムの上端にのせ、同じ組成の溶媒で
溶出した。溶出液を20mLずつ分取すると、化合物RP
−1551−1は画分番号29〜32に溶出された。こ
れらの画分を集めた後、減圧下で濃縮乾固し、化合物R
P−1551−1を52mg得た。800 mL of the obtained fermentation culture solution was filtered, 800 mL of methanol was added to the separated cells, and the mixture was stirred and filtered. 800 mL of deionized water was added to the filtrate, and 80 mL of Diaion HP-20ss filled with deionized water was added.
It was passed through a column (registered trademark manufactured by Mitsubishi Kasei). After washing the column with 300 mL of 50% aqueous methanol, 300 mL
Was eluted with a mixed solvent of methanol / acetone (7: 3). The eluate was concentrated under reduced pressure to give 794 mg of a yellow oil. This substance was dissolved in a chloroform solution containing a small amount of 10% 2-butanone, and 100 mL of silica gel (Merck, Art.773 manufactured by Merck Co., Ltd.) was filled with a solvent having the same composition.
4) It was placed on the top of the column and the active substance was eluted using the solvent of the same composition. When 20 mL of the eluate was collected, compound RP-1551-1 was eluted in fraction numbers 16 to 32. These fractions were collected and concentrated to dryness under reduced pressure to 1
34 mg of yellow solid was obtained. This material was dissolved in a small amount of 70% acetonitrile aqueous solution, and 150 mL of reverse-phase silica gel (YMC, ODS) filled with a solvent having the same composition was used.
-AQS50) was placed on the upper end of the column and eluted with a solvent of the same composition. If 20 mL of the eluate is collected, the compound RP
-1551-1 was eluted in fraction numbers 29-32. After collecting these fractions, they were concentrated to dryness under reduced pressure to give compound R
52 mg of P-1551-1 was obtained.
【0048】実施例2 種菌として、ペニシリウム・エスピー(Penicillium s
p.)SPC−21609株(FERM BP-4768)を用い、第一
種培地としてマッシュポテトの素(雪印乳業社製)3g
/dL、グルコース10g /dL、酵母エキス0.5g /dL
(pH6.5)の組成からなる培地を用いた。種菌一白
金耳を太型試験管に入れた上記第一種培地10mLに植菌
し、25℃で7日間振盪培養した(第一種培養)。[0048] As Example 2 seed, Penicillium sp. (Penicillium s
p.) SPC-21609 strain (FERM BP-4768) was used, and 3 g of mashed potato broth (Snow Brand Milk Products Co., Ltd.) was used as the first type medium.
/ DL, glucose 10g / dL, yeast extract 0.5g / dL
A medium having a composition of (pH 6.5) was used. The inoculum 1 platinum loop was inoculated into 10 mL of the above-mentioned type 1 medium contained in a thick test tube, and cultured by shaking at 25 ° C for 7 days (type 1 culture).
【0049】第一種培養により得られた培養液(第一種
培養液)5mLを300mL三角フラスコに入った50mLの
第二種培地に植菌した。第二種培地の組成は第一種培地
の組成と同じである。第二種培養は25℃で3日間行っ
た。得られた第二種培養液50mLを2L 三角フラスコに
入った400mLの主発酵培地に植菌した。主発酵培地と
して、シュークロース3g /dL、可溶性澱粉2g /dL、
乾燥酵母(アサヒビール社製)0.5g /dL、麦芽エキ
ス1g /dL、コーン・スチープ・リカー0.5g /dL、
野菜ジュース(Campbell社製)20mL/dL 、炭酸カルシ
ウム1.5g /dL(pH6.5)の組成からなる培地を用
いた。主発酵培養は25℃で7日間振盪培養することに
より行った。5 mL of the culture solution (first culture solution) obtained by the first culture was inoculated into 50 mL of the second culture medium contained in a 300 mL Erlenmeyer flask. The composition of the second type medium is the same as that of the first type medium. The second seed culture was carried out at 25 ° C. for 3 days. 50 mL of the obtained second seed culture was inoculated into 400 mL of the main fermentation medium contained in a 2 L Erlenmeyer flask. As main fermentation medium, sucrose 3 g / dL, soluble starch 2 g / dL,
Dry yeast (Asahi Breweries) 0.5 g / dL, malt extract 1 g / dL, corn steep liquor 0.5 g / dL,
A medium having a composition of 20 mL / dL of vegetable juice (Campbell) and 1.5 g / dL of calcium carbonate (pH 6.5) was used. The main fermentation culture was performed by shaking culture at 25 ° C. for 7 days.
【0050】得られた発酵培養液8L をろ過し、分別し
た菌体に8L のメタノールを加え撹拌後ろ過した。ろ液
に8L の脱イオン水を添加し、脱イオン水を用いて充填
した3L のダイヤイオンHP−20ss(三菱化成社製:
登録商標)カラムに通塔した。カラムを50%メタノー
ル水溶液9L で洗浄後、9L のメタノール/アセトン混
合溶媒(7:3)で溶出した。溶出液を減圧下で濃縮し
て、8.3g の黄色油状物質を得た。この物質を少量の
クロロホルム溶液に溶解し、同じ組成の溶媒を用いて充
填した1L のシリカゲル(メルク社製、Art.7734)カラ
ムの上端にのせ、3L のクロロホルム、3L の10%の
2−ブタノンを含むクロロホルム、9Lの20%の2−
ブタノンを含むクロロホルムおよび3L のメタノールで
順次溶出し、溶出液を1L ずつ分取した。画分番号4お
よび画分番号7〜15をそれぞれ減圧下で乾固し、黄色
油状物質をそれぞれ382mgおよび1.8g 得た。画分
番号4より得られた油状物質を少量のクロロホルムに溶
解し、シリカゲル(メルク社製、Lichroprep Si60 )カ
ラムの上端にのせ、クロロホルムで溶出した。溶出容量
180mL〜370mLの間にRP−1551−3が溶出さ
れた。溶出液を減圧下で乾固し、RP−1551−3の
粗精製標品を66mg得た。得られた粗精製標品を85%
メタノール水溶液に溶解し、同じ組成の溶媒で平衡化し
たカラム(YMC社製、D−ODS−5AQ、2cmφ
×25cm)の上端にのせ、85%メタノール水溶液を
毎分10mLの流速で流すことによりRP−1551−3
を溶出した。RP−1551−3は保持時間23分に溶
出され、溶出液を集め減圧下で乾固することにより、R
P−1551−3の粉末を22mg得た。8 L of the obtained fermentation culture broth was filtered, 8 L of methanol was added to the separated cells, and the mixture was stirred and filtered. 8 L of deionized water was added to the filtrate, and 3 L of Diaion HP-20ss (manufactured by Mitsubishi Kasei: filled with deionized water:
It was passed through a (registered trademark) column. The column was washed with 9 L of 50% methanol aqueous solution and then eluted with 9 L of a methanol / acetone mixed solvent (7: 3). The eluate was concentrated under reduced pressure to obtain 8.3 g of a yellow oily substance. This substance was dissolved in a small amount of chloroform solution and placed on the top of a 1 L silica gel (Merck, Art.7734) column packed with a solvent of the same composition, 3 L chloroform, 3 L 10% 2-butanone. Chloroform containing 9 L of 20% 2-
Chloroform containing butanone and 3 L of methanol were sequentially eluted, and 1 L of the eluate was collected. Fraction No. 4 and Fraction Nos. 7 to 15 were dried under reduced pressure to obtain 382 mg and 1.8 g of yellow oily substances, respectively. The oily substance obtained from Fraction No. 4 was dissolved in a small amount of chloroform, placed on the upper end of a silica gel (Lichroprep Si60 manufactured by Merck & Co.) column, and eluted with chloroform. RP-1551-3 was eluted between the elution volumes of 180 mL and 370 mL. The eluate was dried under reduced pressure to obtain 66 mg of a crudely purified sample of RP-1551-3. 85% of the obtained crude purified sample
A column dissolved in an aqueous solution of methanol and equilibrated with a solvent having the same composition (Y-MC, D-ODS-5AQ, 2 cmφ).
RP-1551-3 by placing it on the upper end of (25 cm) and flowing an 85% aqueous methanol solution at a flow rate of 10 mL / min.
Was eluted. RP-1551-3 was eluted at a retention time of 23 minutes, and the eluate was collected and dried under reduced pressure to give R
22 mg of powder of P-1551-3 was obtained.
【0051】前述の画分番号7〜15を濃縮乾固して得
られた油状物質を少量の85%メタノール水溶液に溶解
し、同じ組成の溶媒で平衡化した逆相シリカゲル(YM
C社製、ODS AQ−S50)カラム150mLの上端
にのせ、同じ組成の溶媒を用いて溶出した。溶出液を1
4mLずつ分画するとRP−1551−4は画分番号19
〜22に、RP−1551−2は画分番号23〜27
に、RP−1551−1は画分番号29〜34に溶出さ
れた。各画分をそれぞれまとめて減圧下で濃縮乾固し、
RP−1551−4の粗精製標品を111mg、RP−1
551−2の粗精製標品を169mg、RP−1551−
1を787mg得た。RP−1551−4の粗精製標品を
少量の85%メタノール水溶液に溶解し、HPLCカラ
ム(YMC社製、D−ODS−5AQ、2cmφ×25
cm)に通塔した。カラムを85%メタノール水溶液を
用いて、10mL/分の流速で溶出すると、RP−155
1−4は保持時間16〜18分に溶出された。溶出液を
まとめ、減圧下で濃縮乾固しRP−1551−4を37
mg得た。The oily substance obtained by concentrating and drying the above-mentioned fractions Nos. 7 to 15 was dissolved in a small amount of 85% aqueous methanol solution and equilibrated with a solvent having the same composition as reversed phase silica gel (YM.
C, ODS AQ-S50) column (150 mL) was placed on the upper end of the column and eluted with a solvent having the same composition. Eluate 1
Fractionation by 4 mL yields RP-1551-4 with fraction number 19
~ 22, RP-1551-2 is fraction number 23-27
In addition, RP-1551-1 was eluted in fraction numbers 29 to 34. Concentrate each fraction together under reduced pressure to dryness,
111 mg of the crude purified sample of RP-1551-4, RP-1
169 mg of the crude purified sample of 551-2, RP-1551-
787 mg of 1 was obtained. A crude purified sample of RP-1551-4 was dissolved in a small amount of 85% methanol aqueous solution, and an HPLC column (YMC, D-ODS-5AQ, 2 cmφ × 25) was used.
cm). The column was eluted with 85% aqueous methanol solution at a flow rate of 10 mL / min to give RP-155.
1-4 were eluted at a retention time of 16-18 minutes. The eluates were combined, concentrated to dryness under reduced pressure, and RP-1551-4 was added to 37%.
mg was obtained.
【0052】RP−1551−2の粗精製標品を少量の
85%メタノール水溶液に溶解し、RP−1551−4
の精製過程と同条件での分画を行った。RP−1551
−2は保持時間18.5〜20.5分に溶出され、溶出
液を集めて減圧下で濃縮乾固することにより、RP−1
551−2を47mg得た。A crudely purified sample of RP-1551-2 was dissolved in a small amount of 85% aqueous methanol solution to prepare RP-1554-1.
Fractionation was performed under the same conditions as in the purification process of. RP-1551
-2 was eluted at a retention time of 18.5 to 20.5 minutes, and the eluate was collected and concentrated to dryness under reduced pressure to give RP-1.
47 mg of 551-2 was obtained.
【0053】[0053]
【発明の効果】本発明によれば、抗菌活性を有する化合
物RP−1551類を提供することができる。INDUSTRIAL APPLICABILITY According to the present invention, compounds RP-1551s having antibacterial activity can be provided.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 FI 技術表示箇所 C12P 17/06 7432−4B 17/18 D 7432−4B (C12P 17/06 C12R 1:80) (C12P 17/18 C12R 1:80) (72)発明者 安藤 勝彦 東京都町田市旭町1−17−8 (72)発明者 松田 譲 東京都小金井市貫井南町1−22−7 (72)発明者 北 克則 静岡県駿東郡長泉町竹原255−7 (72)発明者 鈴木 保博 静岡県沼津市下香貫浜田2978−18 (72)発明者 見原 明 東京都町田市木曽町1079−22─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 6 Identification code Internal reference number FI Technical display location C12P 17/06 7432-4B 17/18 D 7432-4B (C12P 17/06 C12R 1:80) ( (C12P 17/18 C12R 1:80) (72) Inventor Katsuhiko Ando 1-17-8 Asahi-cho, Machida-shi, Tokyo (72) Inventor Yuzuru Matsuda 1-22-7 Nunui-cho, Koganei-shi, Tokyo (72) Inventor Katsunori Kita 255-7 Takehara, Nagaizumi-cho, Sunto-gun, Shizuoka (72) Inventor Yasuhiro Suzuki 2978-18 Shimokanuki Hamada, Numazu-shi, Shizuoka (72) Inventor Akira Mihara 1079-22 Kiso-cho, Machida-shi, Tokyo
Claims (5)
I) 【化2】 (式中、2’位水素および5’位水素は8位水素とそれ
ぞれanti配置の関係にある)を表すか、(2)R1
が水素を表し、R2 が式(III) 【化3】 を表すか、(3)一体となって式(IV) 【化4】 を表すか、または(4)一体となって式(V) 【化5】 を表す}で表される化合物RP−1551類。1. Formula (I): {In the formula, R 1 and R 2 are integrated by (1) into the formula (I
I) [Chemical formula 2] (Wherein the 2'-position hydrogen and the 5'-position hydrogen have an anti-configuration relationship with the 8-position hydrogen, respectively) or (2) R 1
Represents hydrogen and R 2 is of the formula (III): Or (3) taken together as a formula (IV) Or (4) together form the formula (V) The compound RP-1551s represented by.
I)を表す請求項1記載の化合物。2. R 1 and R 2 together form the formula (I
A compound according to claim 1 which represents I).
を表す請求項1記載の化合物。3. R 1 represents hydrogen and R 2 is of the formula (III)
The compound according to claim 1, which represents
V)を表す請求項1記載の化合物。4. R 1 and R 2 together form the formula (I
A compound according to claim 1 which represents V).
を表す請求項1記載の化合物。5. R 1 and R 2 together form the formula (V)
The compound according to claim 1, which represents
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP7208649A JPH08109182A (en) | 1994-08-18 | 1995-08-16 | Compound rp-1551s |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP19415194 | 1994-08-18 | ||
JP6-194151 | 1994-08-18 | ||
JP7208649A JPH08109182A (en) | 1994-08-18 | 1995-08-16 | Compound rp-1551s |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH08109182A true JPH08109182A (en) | 1996-04-30 |
Family
ID=26508341
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP7208649A Withdrawn JPH08109182A (en) | 1994-08-18 | 1995-08-16 | Compound rp-1551s |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH08109182A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103910708A (en) * | 2014-02-28 | 2014-07-09 | 中山大学 | Marine fungus-derived Azaphilones compound, and preparation method and application thereof |
-
1995
- 1995-08-16 JP JP7208649A patent/JPH08109182A/en not_active Withdrawn
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103910708A (en) * | 2014-02-28 | 2014-07-09 | 中山大学 | Marine fungus-derived Azaphilones compound, and preparation method and application thereof |
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