Pyridoacridine alkaloids from deep-water marine organisms

29 Pages·2016·9.88 MB·English

BulletinofFacultyofPharmacy,CairoUniversity(2016)54,107–135
Cairo University
Bulletin of Faculty of Pharmacy, Cairo University
www.elsevier.com/locate/bfopcu
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REVIEW PAPER
Pyridoacridine alkaloids from deep-water marine
organisms: Structural elucidation
Sabrin R.M. Ibrahima,b,*, Gamal A. Mohamedc,d
aDepartment ofPharmacognosy andPharmaceutical Chemistry, Collegeof Pharmacy,TaibahUniversity, Al Madinah
AlMunawwarah 30078,Saudi Arabia
bDepartmentof Pharmacognosy,Facultyof Pharmacy,Assiut University, Assiut 71526,Egypt
cDepartmentof NaturalProductsandAlternative Medicine, FacultyofPharmacy,King AbdulazizUniversity, Jeddah21589,
SaudiArabia
dDepartmentof Pharmacognosy,Facultyof Pharmacy,Al-Azhar University, Assiut Branch,Assiut 71524,Egypt
Received 22June 2016; revised24August 2016; accepted31August 2016
Available online22September 2016
KEYWORDS Abstract Pyridoacridine alkaloids are unique marine nitrogenous compounds that represent a
largefamilyofalkaloids.Theyhavebeenreportedfromdifferentmarine organismslikesponges,
Alkaloids;
Pyridoacridine; ascidians, anemones, prosobranch mollusk, and tunicates. Attention to pyridoacridines has risen
Marineorganisms; because of their significant biological activities. The present review emphasizes mainly on pyri-
NMRspectraldata doacridines isolated marine organisms over the last years. Thus, the synthetic ones were not dis-
cussed. Herein, 95 pyridoacridine alkaloids isolated from marine organisms have been retrieved,
in addition to their classification, isolation, sources, structures, molecular weight, physical, and
(UV,IR,1Hand13CNMR)spectraldata.
(cid:1)2016PublishingservicesprovidedbyElsevierB.V.onbehalfofFacultyofPharmacy,CairoUniversity.
ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-
nd/4.0/).
Contents
1. Introduction.. . .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. . .. .. .. .. .. .. .. . . 108
2. Isolation andstructural characterizationof pyridoacridines.. .. .. .. .. .. . .. .. .. .. .. .. . .. .. .. .. .. .. .. . . 129
2.1. Ultraviolet visiblespectroscopy (UV) . .. .. .. .. .. .. .. . .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. 129
2.2. Infraredspectroscopy (IR).. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. 130
2.3. NMRspectroscopy. .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. 130
2.4. Massspectroscopy (MS) . .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. 133
* Corresponding author at: Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al
MadinahAlMunawwarah30078,SaudiArabia.Fax:[phone].
E-mailaddress:[email protected](S.R.M.Ibrahim).
PeerreviewunderresponsibilityofFacultyofPharmacy,CairoUniversity.
http://dx.doi.org/10.1016/j.bfopcu.2016.08.003
1110-0931(cid:1)2016PublishingservicesprovidedbyElsevierB.V.onbehalfofFacultyofPharmacy,CairoUniversity.
ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
108 S.R.M. Ibrahim, G.A.Mohamed
2.5. Stereochemistry determination. .. .. .. .. .. .. . .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. 133
Conflict ofinterest. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. 134
References. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. .. .. .. . .. .. .. .. 134
1. Introduction tant metabolites with significant bioactivities. Marine organ-
isms yield various toxic metabolites in order to prevent
Secondary metabolites from natural sources still provide parasitismandpredationaswellastomediatespatialcompe-
potentialdrugcandidateswithuniqueskeletonsthatareinter- tition.1,2 Among these toxic metabolites are pyridoacridines.
estingformanysyntheticapproaches.Chemistryresearchesof They are the largest group of alkaloids isolated from marine
marinenaturalproductshaveyieldedgreatnumbersofimpor- organisms. They have been reported from sponges, ascidians,
anemones,tunicates,andprosobranchmollusk,whicharedec-
oratedwithbrightcolors.3,4Theyhavedifferentcolors:yellow,
deepred,orange,blue,orpurple.Theircolorswereattributed
2 2
to the presence of pyridoacridines. Pyridoacridines colors
1 3 1 A 3
A changeaccordingtothepH.So,theymaybeusedasanindi-
1111a 4 1111a 4 cator.Thispropertyisduetothepresenceofbasicnitrogenin
HN N
B 4a B 4a thepyridinering thatassociatedwithachromophore. Gener-
10a 10b 4b 10a 10b 4b ally, pyridoacridines are crystalline compounds with melting
10 C D 5 10 C D 5 points >300(cid:3)C. They were isolated as salts of hydrochloric
acid. The optical activity of some pyridoacridines is due to
9 7a N 6 9 7a N 6 the additional asymmetric side chain. They are planar poly-
8
8 1a 7 O 1b 7 cyclic heteroaromatic compounds, having 11H-pyrido[4,3,2,
mn]acridine (1) or 8H-pyrido[4,3,2-nm]acridone (2) skeletons
(Fig. 1), usually possessing different alkylamine side chains
Figure1 Basicskeletonsofpyridoacridinealkaloids.
Table1 Tetracyclicpyridoacridinealkaloids.
Pantherinine(1)
2 Br
3
1 Purplepowder;IR(KBr)m :3810(br),3720(br),1665(w),1630(s)cm(cid:1)1;UV(MeOH)k (e):
max max
11N11a 4a 4 2H5-41)(,176.,91610()d,d3,16J(=3985.08),,14.782H(bzr,,H16-22)0,)8n.9m9;(1dH,JN=MR1.8(DHMz,SHO--4d)6,,83.0907M(dH,Jz)=:dH5.75.H87z,(dH,-J5=),98..178H(dz,,
10 10a 10b 4b 5 J=5.5Hz,H-6),6.58(s,H-10),6.60,8.46(NH);1HNMR(CDCl3/CD3OD,300MHz):dH7.82(d,
J=8.7Hz,H-1),7.89(dd,J=8.7,2.1Hz,H-2),8.72(d,J=2.1Hz,H-4),8.69(d,J=5.7Hz,H-
6
H2N 9 8 7a N 5),9.10(d,J=5.7Hz,H-6),6.64(s,H-10);SouthAustraliaascidianAplidiumpantherinum34
7
O
Pantherinineacetate(2)
2 Br Redglass:UV(MeOH)k (e):255(5794),293(2811),432(1369)nm;IR(KBr)m :3340,1700
3 max max
1 (w),1655(s),1521(s)cm(cid:1)1;1HNMR(CDCl,500MHz):d 8.12(d,J=8.5Hz,H-1),7.98(dd,
3 H
11a
11N 4 J=8.5,2.0Hz,H-2),8.66(d,J=2.0Hz,H-4),8.55(d,J=5.5Hz,H-5),9.29(d,J=5.5Hz,H-6),
4a 8.82(s,H-10),8.50(NH),2.38(CH);13CNMR(CDCl,125MHz):d 132.21(C-1),135.17(C-2),
O 10 10a 10b 4b 5 122.31(C-3),125.91(C-4),123.37(C3-4a),136.01(C-4b),3120.75(C-5),1C50.03(C-6),144.79(C-7a),
178.32(C-8),151.34(C-9),121.78(C-10),137.06(C-10a),116.33(C-10b),144.91(C-10c),170.38(Ac);
NH 9 O8 7a N7 6 LARplMidiSumm/pzan(%the):ri3n6u9m(3245),367(24),327(96),325(100),300(63),298(67);SouthAustraliaascidian
CystodytinA(3)
2 Yellowcrystals;mp181–183(cid:3)C;UV(MeOH)k (e):225(35,000),272(25,000),380(11,400)nm;
max
1 3 IR(KBr)m :3290,2925,2850,1660,1640,1590,1520,1330,1300,1180,860,760cm(cid:1)1;1HNMR
max
1111a 4a 4 (CDCl/CDOD(2:1),400MHz):d 8.07(dd,J=8.2,1.4Hz,H-1),7.76(ddd,J=8.2,8.1,1.3Hz,
14 N 3 3 H
H H-2),7.64(ddd,J=8.1,8.1,1.4Hz,H-3),8.30(dd,J=8.1,1.3Hz,H-4),8.22(d,J=5.5Hz,H-5),
18 17 16 N 12 1010a 10b 4b 8.81(d,J=5.5Hz,H-6),3.08(t,J=6.4Hz,H-12),3.59(t,J=6.4Hz,H-13),6.01(brs,H-14),5.50
19 O15 133 9 87a N 56 ((CqqD,CJl=3/C1D.43,O1D.3(H2:z1,)H,1-0106)M,1H.6z5):(ddC,J13=1.61.(4CH-1z),,H13-11.87),(C1.-923),(1d2,9J.8=(C1-.33),H1z2,2H.8-1(C9)-;41)3,C12N1.M3(RC-4a),
O 7 136.9(C-4b),119.4(C-5),149.0(C-6),145.8(C-7a),183.2(C-8),132.0(C-9),152.4(C-10),149.8(C-
10a),117.5(C-10b),145.0(C-11a),31.3(C-12),38.4(C-13),167.8(C-15),118.1(C-16),150.8(C-17),
26.7(C-18),19.4(C-19);EIMSm/z:359[M+2]+,357[M]+,328,273,260,247;HRFABMSm/z:
360.1707[M+H+2H]+(calcdforC H ON 360.1712);OkinawantunicateCystodytes
22 22 2 3
dellechiajei20
Pyridoacridine alkaloids from deep-water marineorganisms 109
Table1(continued)
CystodytinB(4)
2` Yellowcrystals;mp181–183(cid:3)C;UV(MeOH)k (e):225(35,000),272(25,000),380(11,400)nm;
max
1` 3` IR(KBr)m :3290,2925,2850,1660,1640,1590,1520,1330,1300,1180,860,760cm(cid:1)1;1HNMR
18` 1H4` 1N1` 11a`4a` 4` (HC-D20C),l73/.6C4Dm(3daOxdDd,(J2=:1),84.10,08M.1,H1z.7):HdHz,8H.0-730()d,d8,.3J4=(d8d.,2J,1=.78H.1z,,1H.3-1H0)z,,7H.7-64(0)d,d8d.3,3J(=d,8J.2=,85.1.5,1H.3z,HHz-,
19` 17` 16`O15`N413` 12`91`0` 108a``170ab``N4b` 56`` 56130.)C1,98N(.q8M9q,R(Jd,(=CJD=6.C95l,3.1/5C.5HDHz3,OzH,DH-6-(012),7:160)).,,6117.06(0s0,M(HdHq-9,z0J)),:=3d.C1111.53(,t1,1.3J.2(=CH-z61,.04)H,H-113z81,0.)H8,1-(1.C52-102),(0)d3,q.16,20J9(.=t8,(J6C.=9-3,061),..421H2H2zz.,,8HH(C--11-493000))),;,
O 7` 121.4(C-40a),137.0(C-40b),119.5(C-50),149.1(C-60),183.2(C-80),145.9(C-70a),132.0(C-90),152.5
(C-100),149.9(C-100a),117.5(C-100b),145.0(C-110a),30.9(C-120),39.3(C-130),170.3(C-150),130.3
(C-160),130.0(C-170),11.9(C-180),13.4(C-190);EIMSm/z:359[M+2]+,357[M]+,328,273,260,
247;HRFABMSm/z:360.1707[M+H+2H]+(calcdforC H ON 360.1712);Okinawantunicate
22 22 2 3
Cystodytesdellechiajei20
CystodytinC(5)
2 Lightyellowcrystals;mp257–259(cid:3)C;UV(MeOH)k (e):228(29,900),272(29,100),380(11,800)
max
1 3 nm;IR(KBr)m :3400,2930,2850,1660,1640,1580,760cm(cid:1)1;1HNMR(CDCl/CDOD(2:1),
max 3 3
1111a 4a 4 400MHz):d 8.25(d,J=8.2Hz,H-1),7.90(dd,J=8.2,8.0Hz,H-2),7.81(dd,J=8.0,8.0Hz,H-
14 N H
H 3),8.50(d,J=8.0Hz,H-4),8.44(d,J=5.5Hz,H-5),9.04(d,J=5.5Hz,H-6),6.86(s,H-9),3.25
18 17 16 N 12 1010a 10b 4b (t,J=6.4Hz,H-12),3.75(t,J=6.4Hz,H-13),2.29(s,H-16),1.19(s,H-18,19);13CNMR(CDCl/
19 OH O15 135 9 87a N 56 C(CD-53)O,D14(92.:51)(,C1-060),M14H5.z3):(dCC-71,3111.7a)(,C1-18,3.25),(1C2-98.)8;(1C32-3.4),(1C2-29.9),1(C53-.42),(1C2-11.01),(C14-49a.9),(1C3-71.02a()C,-141b7).,011(C9.-35
O 7 10b),31.4(C-12),38.6(C-13),172.7(C-15),47.6(C-16),65.0(C-17),28.9(C-18),28.9(C-19);EIMS
m/z:377[M+2H]+,375[M]+,373,328,315,273,259,247;OkinawantunicateCystodytes
dellechiajei20
CystodytinD(6)
2 Brown-coloredamorphoussolids;[a]30 (cid:1)160(c0.3,CHCl);UV(MeOH)k (e):214(37,000),274
D 3 max
1 3 (30,000),384(11,000)nm;IR(KBr)m :3400,2930,2850,1650cm(cid:1)1;1HNMR(DMSO-d,400
max 6
18 16 1HN4 OH 1N1 11a 44ba 4 M(s,HHz-)9:)d,H5.85.62(4m(d,,HH-1-12)),,47..1964((mdd,,HH--123)A,7),.634.9(6dd(m,H,H-3-)1,38B.9)4,6(.d0,7H(m-4,),H8-.1349)(,d5,.6H2-(5b),rs9,.1H0-1(d6,),H1-.664),(7b.r2s0,
17 15 13 12 10 10a 10b 5 H-18),2.16(m,H-19);13CNMR(DMSO-d6,100MHz):dC131.7(C-1),131.9(C-2),129.9(C-3),
O 6 9 6 123.0(C-4),121.8(C-4a),137.1(C-4b),119.2(C-5),150.1(C-6),144.9(C-7a),183.5(C-8),131.2(C-
19 8 7a N7 9),150.0(C-10),146.7(C-10a),117.4(C-10b),144.9(C-11a),71.2(C-12),41.6(C-13),169.3(C-15),
O 117.4(C-16),153.4(C-17),27.3(C-18),20.0(C-19);FABMSm/z:376[M+2H]+,358[M-HO
2
+2H]+;HRFABMSm/z:376.1669[M+2H]+(calcdforC H NO 376.1661);Okinawanmarine
22 22 3 3
tunicateCystodytesdellecbiajei12
CystodytinE(7)
2
1 3
Brown-coloredamorphoussolids;[a]30 (cid:1)160(c0.3,CHCl);UV(MeOH)k (e):214(37,000),274
18 1H4 OH 1N1 4a 4 (30,000),384(11,000)nm;IR(KBr)mmDax:3400,2930,28503,1650cm(cid:1)1;1HmNaxMR(DMSO-d6,400
19 N 4b MHz):d 6.36(m,H-14),6.48(m,H-17),1.82(brs,H-18),1.73(dd,J=6.9,1.1Hz,H-19);FABMS
15 10 10b H
17 16 13 12 10a 5 m/z:376[M+2H]+,358[M-H2O+2H]+;HRFABMSm/z:376.1669[M+2H]+(calcdfor
O 7 9 6 C H NO 376.1661);OkinawanmarinetunicateCystodytesdellecbiajei12
8 7a N 22 22 3 3
7
O
CystodytinF(8)
2 Yellow-coloredamorphoussolids;[a]30(cid:1)133(c0.3,CHCl);UV(EtOH)k (e):225(30,000),272
D 3 max
1 3 (23,000),380(11,000)nm;IR(KBr)m :3330,2940,2850,1660,1590,1175,1110cm(cid:1)1;1HNMR
max
1H4 OCH3 1N1 4a 4 (JC=DC8.l13,,410.80HMz,HHz)-:4d),H87.5.982(d(d,tJ,=J=5.47.H3,z1,.H0H-5z),,9H.2-25),(d7,.8J2=(d5t,.4JH=z,8H.3-,61),.07H.1z2,(Hs,-H3)-,98).,559.4(0dd(,t,
18 16 N 4b
17 15 13 12 10 10a 10b 5 J=4.9Hz,H-12),3.99(ddd,J=14.0,5.4,3.9Hz,H-13A),3.82(ddd,J=14.0,6.4,5.4Hz,H-
19 O 8 9 8 7a N 6 1O3CBH),5);.8163C(mN,MH-R14()C,5D.5C7l(,b1rs0,0HM-1H6)z,)2:.d001(d3,0J.1=(Cl-.10)H,1z3,2H.2-1(8C),-21).,8112(9d.,9J(C=-32).,01H22z.,0H(C-1-94)a,)3,.15307(.s4,
7 3 3 C
O (C-4b),119.5(C-5),151.2(C-6),146.8(C-7a),183.8(C-8),131.7(C-9),150.1(C-10),149.7(C-10a),
118.2(C-10b),145.4(C-11a),76.72(C-12),43.25(C-13),167.0(C-15),118.4(C-16),150.8(C-17),
27.09(C-18),19.77(C-19),57.75(OCH);EIMSm/z:389[M+2H]+,357,328,302,277,262,247;
3
HREIMSm/z:389.1749[M+2H]+(calcdforC H ON 389.1740);Okinawanmarinetunicate
23 23 3 3
Cystodytesdellecbiajei12
(continuedonnextpage)
110 S.R.M. Ibrahim, G.A.Mohamed
Table1(continued)
CystodytinG(9)
2
Yellow-coloredamorphoussolids;[a]30(cid:1)133(c0.3,CHCl);UV(EtOH)k (e):225(30,000),272
1 3 D 3 max
(23,000),380(11,000)nm;IR(KBr)m :3330,2940,2850,1660,1590,1175,1110cm(cid:1)1;1HNMR
18 1H4 OCH3 N11 4a 4 (CDCl3,400MHz):dH6.37(dd,J=m6a.8x,1.5Hz,H-14),6.24(t,J=4.9Hz,H-17),1.78(t,
19 17 16 15 N 13 12 10 10a 10b 4b 5 dJC=1310.2.8H(Cz,-1H7-)1,81)2,.416.7(2C(-d1d8,),J1=3.962.8(,C1-1.29)H,z5,7H.82-1(9O),C3H.532);(Es,IOMCSHm3/)z;:133C89N[MM+R2(HC]D+C,l335,71,0302M8,H30z2):,
O 9 9 8 7a N7 6 277,262,247;HREIMSm/z:389.1749[M+2H]+(calcdforC23H23O3N3389.1740);Okinawan
marinetunicateCystodytesdellecbiajei12
O
CystodytinsH(10)andI(11)
2
O
1 3
18` 11 4
18 716 HN7 O N 44ba Yellow-coloredamorphoussolids;[a]30D(cid:1)29.1(c0.3,CHCl3);UV(EtOH)kmax(e):225(37,000),273
17 15 14 13 12 10 10a 10b 5 (25,000),382(10,000)nm;IR(neat)mmax:3320,2910,2840,1730,1650,1590,1540,1250,1190cm(cid:1)1;
O 10 9 6 1HNMR(CDCl3,400MHz):dH8.32(brd,J=8.3Hz,H-l),7.93(dt,J=7.8,l.5Hz,H-2),7.83(brt,
19 8 7a N J=7.3Hz,H-3),8.58(dd,J=8.1,1.8Hz,H-4),8.57(d,J=5.4Hz,H-5),9.24(d,J=5.4Hz,H-
7
O 6),6.99(s,H-9),6.85(t,J=3.4Hz,H-12),4.14(m,H-13A),3.94(m,H-13B),5.71(m,H-14),5.53
O 2 (brs,H-16),5.35(2H,m,ACH‚CHA),2.83(2H,m,ACH‚CHACH),2.50(2H,t,J=6.3Hz,H-
1 3 20),2.04(2H,m,ACH‚CHACH),1.79(d,J=1.5Hz,H-18),0.88(2t,J=6.3Hz,H-180),1.97(d,
1189` 177161815 1HN47 13 O12 10 11N01a 10b 44ba 45 J+=2H1-.C51H8Hz,33HO-21+9)H,1]+.7,03(528H,,2m74,,C22H632,),2519.2;5O(k2i2nHaw,man,CmHar2i)n;eFtAunBiMcaStemC/yzs:t6o4d0yt[eMsd+el2leHcb]+ia,je3i7124[M
O 11 9 6
8 7a N
7
CystodytinJ(12)
2 Yellowsolid;1HNMR(CDCl,500MHz):d 8.29(d,J=8.1Hz,H-1),7.94(ddd,J=8.1,7.1,
3 H
1 3 1.4Hz,H-2),7.83(ddd,J=8.1,7.1,1.4Hz,H-3),8.42(d,J=8.1Hz,H-4),8.18(d,J=5.5Hz,H-
1N1 11a 4 5),8.94(d,J=5.5Hz,H-6),6.85(s,H-9),3.25(t,J=6.4Hz,H-12),3.79(dt,J=6.4,5.9Hz,H-
1H4 4a 13),6.59(s,H-14),2.02(s,H-16);13CNMR(CDCl,125MHz):d 131.87(C-1),131.87(C-2),129.83
16 N 4b 3 C
15 12 10 10a 10b 5 (C-3),122.84(C-4),121.78(C-4a),136.92(C-4b),118.99(C-5),149.76(C-6),146.48(C-7a),183.31(C-
13
O 12 9 6 8),132.82(C-9),152.17(C-10),150.33(C-10a),117.84(C-10b),145.32(C-11a),31.72(C-12),39.28
8 7a N (C-13),170.43(C-15),23.30(C-16);FABMS(3-nitrobenzylalcohol)m/z:318[M+H]+,247;
7
O FABMS(glycerol)m/z:320[(M+2)+H]+,247;HRFABMS(glycerol)m/z:320.1390[(M+2)+H]+
(calcdforC H NO 320.1399);FijianascidianCystodytessp.35
19 18 3 2
CystodytinK(13)
N7 6 Yellowsolid;[a]D(cid:1)292(c0.065,MeOH);UV–vis(MeOH/TFA)kmax(loge):207(4.57),272(4.17),
5 382(3.67)nm;UV-Vis(MeOH/KOH)k (loge):204(4.46),270(4.17),380(3.71)nm;IRm :
O 87a 10b 4b 4a 4 3 3303,2926,1655,1587,1465,1112,1022mcaxm(cid:1)1;1HNMR(DMSO-d6,300MHz):dH8.25(d, max
J=8.3Hz,H-1),8.03(t,J=8.3Hz,H-2),8.02(t,obsc,H-3),8.96(d,J=7.9Hz,H-4),9.06(d,
9 101210a N11 11a 1 2 J7.=945(o.4bHscz,,HH-1-54)),,91..2678((ds,,JH=-205),.53H.42z,(Hs,-O6)C,6H.834);(1s3,CHN-9M),5R.2(8D(Mt,JSO=-d46.,37H5zM,HH-z1)2:)d,C3.15341(.m0,(CH--11)3,),
H3CO 13 131.9(C-2),129.7(C-3),124.1(C-4),121.6(C-4a),137.3(C-4b),120.3(C-5),149.9(C-6),146.0(C-
13 HN14 1` 2` 7a),132.0(C-9),150.5(C-10),146.2(C-10a),117.7(C-10b),144.5(C-11a),76.1(C-12),42.4(C-13),
169.3(C-10),22.3(C-20),56.8(OCH);FABMSm/z:350[M+2H+H]+;HRFABMSm/z:350.1507
O 3
[M+H]+(calcdforC H NO 350.1505);ZealandascidianLissoclinumnotti36
20 20 3 3
Iminoquinone(14)
6 Brownsolid;UV(MeOH-TFA)k (loge):226(3.97),272(3.95),387(3.49)nm;UV(MeOH-KOH)
N7 5 k (loge):268(3.97),376(3.49)nmmax;IRm (film):3072,1678,1202,1131cm(cid:1)1;1HNMR(DMSO-
max max
O 87a 10b 4b 4a 4 3 d6,500MHz):dH8.23(d,J=7.5Hz,H-1),8.03(dd,J=7.5,7.5Hz,H-2),7.94(m,H-3),8.95(d,
J=8.0Hz,H-4),9.05(d,J=5.0Hz,H-5),9.26(d,J=5.0Hz,H-6),7.11(s,H-9),5.67(brm,H-
195 10 1210a N11 11a 1 2 M12H),z3).:5d0C(m13,0H.7-1(3CA-1)),,31.1382.0(m(C,H-2-)1,31B3)0,.07.(9C7-3(m),,1H24-1.14)(,C6-.44)0,1(b21rs.7,H(C-1-45a);),131C36N.7M(CR-4(bD),M1S20O.4-d(6C,1-52)5,
HO 13 150.0(C-6),146.3(C-7a),183.0(C-8),130.9(C-9),149.3(C-10),151.7(C-10a),117.8(C-10b),144.3
14 NH3O2CCF3 (C-11a),64.2(C-12),44.3(C-13);HRFABMS(glycerol)m/z:294.1245[M+2H]+(calcdfor
14 C H NO 294.1243);FABMS(3-nitrobenzylalcohol)m/z(rel.int.):292[M+H]+(100);
17 16 3 2
IndonesianascidianEusynstyelalatericius37
Pyridoacridine alkaloids from deep-water marineorganisms 111
Table1(continued)
StyelsamineA(15)
CF3CO2H 1 2 Purplesolid;UV(MeOH-TFA)kmax(loge):222(sh)(3.86),244(3.71),276(3.93),294(3.96),386
N 3 (3.17),554(3.02)nm;UV(MeOH-KOH)k (loge):272(3.85),378(3.39)nm;IR(KBr)m :3102,
H12O11 11a 11b 3a 3b 4 5 2942,1678,1584,1443,1202,1143cm(cid:1)1;1mHaxNMR(DMSO-d6,500MHz):dH13.70(brs,Hma-x1),8.33
(d,J=6.0Hz,H-2),7.65(d,J=6.0Hz,H-3),8.24(d,J=8.5Hz,H-4),7.24(dd,J=8.0,8.0Hz,
10 913 8a NH8 7a 7 6 H(b-r5s),,H7.-6192)(,d5d.,6J2=(br8d.0,,J8=.0H7.z0,HHz-,6)H,7-1.939),(3d.,0J7=(m8,.H5H-1z4,AH),-72).,8191(.m13,(Hbr-s1,4HB)-,8)8,.178.79(b(rss,,HH-1-105),),160..4978
HO 14 (brs,H-16);13CNMR(DMSO-d,125MHz):d 143.6(C-2),105.5(C-3),149.1(C-3a),113.9(C-3b),
16 6 C
15 NH3O2CCF3 125.4(C-4),122.6(C-5),134.8(C-6),117.9(C-7),140.9(C-7a),126.6(C-8a),118.3(C-9),117.4(C-
15 10),137.3(C-11),127.0(C-11a),120.3(C-11b),64.3(C-13),44.0(C-14);HRFABMS(3-nitrobenzyl
alcohol)m/z:294.1226[M+H]+(calcdforC H NO294.1243);FABMS(3-nitrobenzylalcohol)
17 16 3
(rel.int.)m/z:294[M+H]+;IndonesianascidianEusynstyelalatericius37
StyelsamineB(16)
CF3CO2H N1 2 3 3P.u5r7p)l,e3s8o8li(d3;.7U0V),(5M72eO(3H.7-2T)FnAm);kUmaVx((lMogeOe)H:2-2K2O(Hsh),k4.43),(l2o4g4e()4:.22682),(247.838()4,.5357)8,2(39.497(4).n6m0);,3IR72m(sh,
H12O1111a 11b 3a 3b 4 5 (film):3072,1678,1660,1619,1581,1367,1199,1128mcamx(cid:1)1;1HNMR(DMSO-d6,500MHz):dHmax
13.47(brs,H-1),8.24(d,J=6.5Hz,H-2),7.54(d,J=6.5Hz,H-3),8.20(d,J=8.5Hz,H-4),7.22
10 9138a NH8 7a 7 6 (1d2d),,2J.9=6(7t.,5J,7=.56H.5z,HHz,-5H),-173.7)0,3(.m24,H(d-t6,)J,7=.677.(5m,,6H.5-H7)z,,1H1.-5104)(,b8rs.5,0H(-t8,)J,7=.435.(5s,HHz-,1H0)-,1150),.718.9(1br(ss,,HH--
16 14 17);13CNMR(DMSO-d,125MHz):d 143.3(C-2),104.9(C-3),149.2(C-3a),113.9(C-3b),125.4
6 C
HN 16 17 (C-4),122.0(C-5),135.0(C-6),117.6(C-7),141.0(C-7a),128.3(C-8a),116.2(C-9),121.6(C-10),
15 136.6(C-11),125.9(C-11a),120.3(C-11b),30.3(C-13),37.7(C-14),171.4(C-16),22.4(C-17);
O HRFABMS(3-nitrobenzylalcohol)m/z:320.1397[M+H]+(calcdforC H NO 320.1399);
19 18 3 2
FABMS(3-nitrobenzylalcohol)m/z(rel.int.):320[M+H]+(100),247(15);Indonesianascidian
Eusynstyelalatericius37
StyelsamineC(17)
CF3CO2H 2 Orangesolid;UV(CHCl3)kmax(loge):248(4.90),284(4.82),334(4.22),350(4.27),418(4.75),480
1N 3 (4.41)nm;UV(CHCl-TFA)k (loge):282(4.85),304(4.89),422(4.69),510(4.33)nm;IRm
3 max max
H12O11 11a 11b 3a 3b 4 5 (film):3283,1650,1630,1515,1242cm(cid:1)1;1HNMR(DMSO-d6,500MHz):dH8.80(d,J=5.5Hz,
H-2),7.93(d,J=5.5Hz,H-3),8.33(d,J=8.0Hz,H-4),7.28(m,H-5),7.61(m,H-6),7.61(m,H-
10 913 8a NH8 7a 7 6 M7),H1z2).:1d3C(b1r5s1,.6H(-C8)-,27),.31809(b.3rs(,CH-3-)1,01),409..915(C(b-3rsa,),H1-1162.)7,(9C.9-33b()s,,1H2-41.34);(C13-C4),N1M23R.0((DC-M5)S,O13-d26.6,1(2C5-6),
O H 117.9(C-7),137.1(C-7a),134.6(C-8a),108.4(C-9),113.6(C-10),139.0(C-11),142.8(C-11a),117.9
17
(C-11b),191.8(C-13);HRFABMS(3-nitrobenzylalcohol)263.0814[M+H]+(calcdforC H NO
16 11 2 2
263.0821);FABMS(glycerol)m/z(rel.int.):263[M+H]+(100);IndonesianascidianEusynstyela
latericius37
StyelsamineD(18)
CF3CO2H N1 2 3 3P7u2rp(l3e.5s4o)l,id3;8U6V(3(.6M0)e,O5H60-T(F3.A43))knmmax;(UloVge()M:2e2O2H(4-K.3O0)H,2)3k8(4.1(l7o)g,2e7):62(740.3(74).,2269),43(746.38(3),.9352)0n(m3.;8I0R),
max
H12O1111a 11b 3a 3b 4 5 mmax(film):3072,1672,1584,1202,1131cm(cid:1)1;1HNMR(DMSO-d6,500MHz):dH13.61(brs,H-1),
8.30(d,J=6.5Hz,H-2),7.60(d,J=6.5Hz,H-3),8.23(d,J=8.5Hz,H-4),7.23(m,H-5),7.69
10189 138a NH8 7a 7 6 (1m3),,H3.-160),(b7r.6m9,(Hm-,1H4)-,77).,9150(.b84rs(,bHrs-,15H);-81)3,C7.N47M(Rs,(HD-M10S),O1-0d.69,81(2b5rsM,HH-z1)2:)d,C31.2403.(3br(Ct,-J2)=,1075.0.1H(zC,-H3)-,
14 148.9(C-3a),113.8(C-3b),125.2(C-4),122.4(C-5),134.7(C-6),117.6(C-7),141.0(C-7a),128.3(C-
NH3O2CCF3 8a),113.8(C-9),121.8(C-10),137.2(C-11),126.7(C-11a),120.4(C-11b),28.2(C-13),37.9(C-14);
15 HRFABMS(3-nitrobenzylalcohol)m/z:278.1280[M+H]+(calcdforC H NO278.1293);
17 16 3
FABMS(3-nitrobenzylalcohol)m/z(rel.int.):278[M+H]+(100),261(20),247(15);Indonesian
ascidianEusynstyelalatericius37
Diplamine(19)
6 Burntorangesolid;mp202–204(cid:3)C(dec.);UV(MeOH))k (e):377(5984),300(14,722).263
N7 5 (24,874)nm;IR(neat)m :3323,3066,2984,2923,1651,m1a6x00,1533cm(cid:1)1;1HNMR(CDCl,200
O 87a 10b 4b 4a 4 3 MHz):dH8.46(dd,J=m8a.x0,1.4Hz,H-1),7.92(ddd,J=8.0,8.0,1.2Hz,H-2),7.80(ddd,J=3 8.0,
H31C4S 9 111002a N11 11a 1 2 5860.)0,,M31.7H.43zH()b:zrd,sC,HH1-32-1)2,2.78),6.23(7.C7(3-d1d()b,,r1Js2,=9H.6-813.30(),C,16-.22.4),H51z(3H,1H-.19-434)),(,C18.-.9331)5,((1Hd1,-81J.69=)4,(25C.6.-624H)(,sz,1,2SH1C.-2H58)3,)(;9C1.-034C6a()Nd,,1MJ36R=.5(9D5.(M6CH-S4Ozb,-)Hd,6-,
19 13 131.75(C-5),149.71(C-6),146.39(C-7a),179.43(C-8),143.39(C-9),149.51(C-10),151.70(C-10a),
H1N4 15 16 F11A6B.9M0(SCm-1/0zb:)3,61845[M.49+(C2H-1+1aH),]3+0,.03266(C[M-12+),H39]+.7;5H(CR-F13A)B,1M70S.5m6/(zC:-31656).,12237.932[M(C+-1H6)],+17(.c8a6lc(dSCfoHr3);
O
C H NOS);FijiIslandstunicateDiplosomrasp.29
20 19 3 2
(continuedonnextpage)
112 S.R.M. Ibrahim, G.A.Mohamed
Table1(continued)
Isodiplamine(20)
N7 6 SCH3 Greensolid;mp208–210(cid:3)C;UV–vis(MeOH/TFA)kmax(loge):215(4.68),274(4.16),320(4.01),406
5 (4.00)nm;UV-Vis(MeOH/KOH))k (loge):205(4.57),273(4.20),320(4.03),406(4.04)nm;IR
O 87a 10b 4b 4a 4 3 mmax3297,2923,1652,1566,1525,14m3a0x,1192cm(cid:1)1;1HNMR(DMSO-d6,300MHz):dH8.32(d,
J=7.8Hz,H-1),8.05(t,J=7.1Hz,H-2),8.02(obsc,H-3),9.35(d,J=8.1Hz,H-4),9.13(s,H-6),
9 101210a 1N1 11a 1 2 S6.C8H5(3s);,H13C-9)N,3M.1R7((tD,MJ=SO6-.d46,H7z5,MH-H12z)),:3d.C5213(o1.b7sc(,CH-1-)1,31)3,17..195(C(o-2b)s,c1,2H9.-514()C,-13.)7,41(2s7,.H5(-C20-)4,)2,.91721(.s8,
20 13 (C-4a),132.8(C-4b),138.2(C-5),145.9(C-6),141.7(C-7a),182.6(C-8),131.8(C-9),151.1(C-10),
HN 1` 2` 150.1(C-10a),129.3(C-10b),145.1(C-11a),31.2(C-12),37.8(C-13),169.1(C-10),22.5(C-20),16.4
14 (SCH);FABMSm/z:366[M+2H+H]+,364[M+H]+;HRFABMSm/z:364.1126[M+H]+(calcd
O 3
forC H NOS364.1120);NewZealandascidianLissoclinumnotti36
20 18 3 2
DiplamineB(21)
N7 6 5 2D9a2r4k,2o8r5a3n,g1e6fi7l5m,;12U0V2,(1M13e1O,H72)3kcmmax(cid:1)(1l;o1gHeN):M20R8((4C.3D9)O,2D6,55(030.7M0)H,3z7):9d(3.80.53)4n(dm,;JI=R(8n.e0aHt)zm,mHax-1:),
O 87a 10b 4b 4a 4 3 7.99(t,J=7.7Hz,H-2),7.90(t,J=7.7Hz,H-3),8.803(d,J=7.5Hz,HH-4),8.90(d,J=5.0Hz,H-
H31C4S 9 1100a N 1 2 153)C,9N.1M4(Rd,(CJD=3O4.D4,H1z2,5HM-6H),z3):.8d9C(1t,32J.6=7(7C.4-1H),z1,3H3.-3122)(,C3-.23)7,1(3t,1J.3=9(C7.-23)H,z1,2H4.9-133()C,2-4.6),81(2s3,.H10-1(4C)-;
21 12 4a),139.08(C-4b),122.01(C-5),150.89(C-6),147.71(C-7a),181.05(C-8),144.73(C-9),150.21(C-
13 10),150.72(C-10a),118.76(C-10b),147.07(C-11a),29.09(C-12),40.17(C-13),17.87(C-14);
NH2 HRESITOFMSm/z:322.1005[M+H]+(calcdforC18H16N3OS322.1014);PapuaNewGuinea
ascidianLissoclinumcf.badium38
Nor-segoline(22)
2 UV(MeOH)k (e):440(1200),400(2800),367(1500),340(3000),264(12,700),225(17,300)nm;
N1 3 UV(MeOH,Hm+ax)k (e):515(850),402(2300),385(2300),366(1500),295(10,900),264(12,000),
max
H3CO 11 11a 3a3b 4 5 225(18,900)nm;IR(CHCl3)mmax:2940,1670,1620,1520,1310,1130,1070cm(cid:1)1;1HNMR(CDCl3,
11b 360MHz):d 8.86(d,J=4.8Hz,H-2),7.61(d,J=4.8Hz,H-3),7.18(dd,J=7.9,1.2Hz,H-4),
10 9 8a N8 7a 6 7.48(dt,J=H7.9,1.2Hz,H-5),7.17(dt,J=7.9,1.2Hz,H-6),8.03(d,J=7.9Hz,H-7),11.66(brs,
22 COOCHH39 7 8-NH),7.51(s,H-10),4.00(s,11-OCH3),3.99(s,12-OCH3);13CNMR(CDCl3,90MHz):dC151.9
(C-2),108.7(C-3),145.2(C-3a),116.5(C-3b),130.8(C-4),123.9(C-5),132.3(C-6),122.3(C-7),137.9
(C-7a),137.3(C-8a),117.1(C-9),109.1(C-10),141.1(C-11),123.5(C-11a),119.3(C-11b),168.8(C-
12),56.2(11-OCH),51.9(12-OCH);CIMS(CH)m/z(re1.int.):307[M+H]+(C H NO,100);
3 3 4 18 15 2 3
RedSeatunicateEudistomasp.39,40
Tintamine(23)
2
H1N 3
O
12 12a 3a3b 4 5 OH
11 12b Yellowpowder;IR(KBr)m :3492,3436,3270cm(cid:1)1;1HNMR(CDCl/CDOD(4:1),500MHz):
14 S 10 9 8a N8 7a 7 6 dH3.75(t,J=7.5Hz,H-2)m,a2x.66(t,J=7.5Hz,H-3),6.65(d,J=1.9H3z,H3-4),6.72(dd,J=8.5,
17 1.9Hz,H-6),8.12(d,J=8.5Hz,H-7),6.78(d,J=1.9Hz,H-9),7.18(brs,H-11),3.08(m,H-14),
(H3C)2N 15 13 3.19(m,H-15),2.76(s,H-17);13CNMR(CDCl/CDOD(4:1),125MHz):d 47.4(C-2),26.3(C-3),
3 3 C
1 2 136.1(C-3a),119.1(C-3b),114.3(C-4),160.0(C-5),113.5(C-6),130.6(C-7),140.7(C-7a),151.6(C-
HO N 3 8a),111.8(C-9),137.2(C-10),112.3(C-11),167.0(C-12),159.6(C-12a),142.4(C-12b),31.3(C-14),
12 12a 3a 4 OH 59.0(C-15),43.1(C-17);HRFABMSm/z:368.1390[M+H]+(calcdforC H NOS368.1432);
3b 20 22 3 2
12b 5 IndianOceantunicateCystodytesviolatinctus41
11
8a N 7a 6
14 S 10 9 8 7
17
(H3C)2N 13 23
15
Tintaminediacetate(24)
AcO N1 2 3 A(lomgoer)p:h28o0us(3p.5o2w)d,3er4;0U(3V.5(8M),e3O71H()3.k6m5a)xn(mlo;gIRe):(n2e6a5t)(3m.68):,3350080,(31.76672),n1m02;1UcVm(cid:1)(M1;1eHOHNM+RH(+C)DkCmlax,
max 3
12 12a 12b3a3b 4 5 OAc 500MHz):dH3.95(t,J=7.5Hz,H-2),2.75(d,J=7.5Hz,H-3),7.04(d,J=1.9Hz,H-4),7.09
11 (dd,J=8.5,1.9Hz,H-6),8.55(d,J=8.5Hz,H-7),7.14(d,J=1.9Hz,H-9),7.72(d,J=1.9Hz,
6
8a N 7a H-11),3.25(brt,H-14),3.38(brt,H-15),2.84(s,H-17),2.34(COCH),2.43(COCH);13CNMR
(H137C)2N 14 S1310 924 8 7 (CDCl3,125MHz):dC47.7(C-2),26.1(C-3),119.3(C-4),119.4(C-6),3130.3(C-7),1193.6(C-9),119.7
15 (C-11),31.2(C-14),59.2(C-15),43.3(C-17),20.1(COCH),20.8(COCH),169.1(COCH3);Indian
3 3
OceantunicateCystodytesviolatinctus41
Pyridoacridine alkaloids from deep-water marineorganisms 113
Table1(continued)
VaramineA(25)
2 UV(MeOH)k (e):232(31,500),275(25,800),292(sh),324(sh),382(3530),464(51,701),494(sh);
1617 15 1HN4 13 H1N1 111a 4a 34 (cU2mV0(cid:1),41(0M;01)He,O3NH59M,(HR4m5+a(2xC)0kD),mC3ax7l6(,e(5)4:060242M04),H(52z24)7,:4d(0506)77,.028)27,85(d5(sd2h,()Js,h2=)4;0I8R.(4s,h(C1),.H22C6H3lz3,()sHmhm)-,1ax)2:,8730.405(4s0h,()d3,d22,89J01,=(332180,.014,0,011)6.,3530H3,9z1,6H15-
O 12 10 10a10b4b 5 2),7.43(td,J=8.4,1.32Hz,H-3),7.5H1(d,J=8.4Hz,H-4),7.30(d,J=5.2Hz,H-5),8.67(d,
J=5.2Hz,H-6),10.2(brs,H-11),3.30(m,H-12),3.30(m,H-13),6.22(brs,H-14),2.38(q,
H3CS 9 87a N 6 J=6.5Hz,H-16),1.29(t,J=6.5Hz,H-17),4.05(s,OCH3),2.53(s,S-CH3);1HNMR(CD3OD/
25 OCH3 TFA-d,500MHz):dH8.09(d,J=8.2Hz,H-1),7.27(dd,J=8.2,7.3Hz,H-2),7.66(dd,J=8.3,
7.3Hz,H-3),7.77(d,J=8.3Hz,H-4),7.52(d,J=6.5Hz,H-5),8.21(d,J=6.5Hz,H-6),3.23(m,
H-12),3.33(m,H-13),2.35(q,J=7.6Hz,H-16),1.24(t,J=7.6Hz,H-17),4.00(s,OCH),2.66(s,
3
S-CH);13CNMR(CDOD/TFA-d,125MHz):d 126.2(C-1),124.8(C-2),136.5(C-3),119.5(C-4),
3 3 C
116.0(C-4a),132.6(C-4b),106.4(C-5),143.8(C-6),150.5(C-7a),140.9(C-8),140.5(C-9),119.3(C-
10),134.0(C-10a),120.6(C-10b),142.2(C-11a),29.3(C-12),38.8(C-13),178.8(C-15),30.0(C-16),
10.4(C-17),60.4(OCH),18.7(S-CH);FABMSm/z(re1.int.):394[M+H]+(100),293[M-
3 3
CH NO]+(43);HRMSm/z:394.1592[M+H]+(calcdforC H NOS394.1589);FijiIsland
5 10 22 24 3 2
tunicateLissoclinumvareau9
VaramineB(26)
2 UV(MeOH)k (e):234nm(25,900),274(21,400),292(sh),324(sh),382(3040),462(4320),491
max
16 15 1HN4 13 H1N1 111a 34 3(s6h2);(sUhV),3(M79e(O41H9,0H),+52)9km(4a7x2(0e)):,525223((42203,507)0;)I,R23(C8H(sCh)l,3)2m6m6a(xs:h3)4,5208,23(2s8h0),,3229040(,2176,45000,)1,631171c(m17(cid:1),13;010H),
4a NMR(CDOD/TFA-d,500MHz):d 8.09(d,J=8.2Hz,H-1),7.27(dd,J=8.2,7.3Hz,H-2),
O 12 10 10a10b4b 5 7.66(dd,J3=8.3,7.3Hz,H-3),7.77(Hd,J=8.3Hz,H-4),7.52(d,J=6.5Hz,H-5),8.21(d,
J=6.5Hz,H-6),3.23(m,H-12),3.33(m,H-13),2.08(s,H-16),4.00(s,OCH),2.66(s,S-CH);13C
H3CS 9 87a N 6 NMR(CD3OD/TFA-d,125MHz):dC126.2(C-1),124.8(C-2),136.5(C-3),1193.5(C-4),116.0(3C-4a),
26 OCH3 132.6(C-4b),106.4(C-5),143.8(C-6),150.5(C-7a),140.9(C-8),140.5(C-9),119.3(C-10),134.0(C-
10a),120.6(C-10b),142.2(C-11a),29.3(C-12),38.8(C-13),175.2(C-15),22.5(C-16),60.4(OCH),
3
18.7(S-CH);FABMSm/z:380[M+H]+(100);HRMSm/z:380.1420[M+H]+(calcdfor
3
C H NOS380.1433);FijiIslandtunicateLissoclinumvareau9
21 22 3 2
Table2 Pentacyclicpyridoacridinealkaloids.
KuanoniamineA(27)
2 Yellowneedles;mp255–258(cid:3)C(dec);UV(MeOH)k (loge):214(4.26),224(4.28),250
max
N 3 (4.20),258(4.19),295(3.80),354(3.76),394(3.61)nm;UV(MeOH,H+)k (loge):208
max
N 12a 12b 3a3b 4 5 (4.21),226(4.25),244(sh,4.17),292(4.17),382(3.71)nm;IR(CHCl3)mmax:3020,1680,
11 12c 1590,1290,1240,1220,1050,800,750cm(cid:1)1;1HNMR(DMSO-d6,300MHz):dH8.69(d,
S 9a 9 8a N 7a 7 6 J=6.0Hz,H-2),8.45(d,J=6.0Hz,H-3),8.58(d,J=8.1Hz,H-4),7.60(dd,J=8.1,
O 27 7.6Hz,H-5),7.66(dd,J=7.8,7.6Hz,H-6),8.01(d,J=7.8Hz,H-7),9.28(s,H-11);
13CNMR(DMSO-d,75MHz):d 149.04(C-2),117.28(C-3),137.21(C-3a),123.07(C-
6 C
3b),124.08(C-4),131.02(C-5),132.02(C-6),132.02(C-7),144.87(C-7a),147.27(C-8a),
176.17(C-9),135.21(C-9a),162.72(C-11),157.84(C-12a),147.12(C-12b),116.45(C-
12c);HREIMSm/z:289.0307(calcdforC HN0S289.0305),261.0352(Calcdfor
16 7 3
C HNS261.0344),234.0249(calcdforC HNS234.0246);EIMSm/z(rel.int.):261
15 7 3 14 6 2
(42),234(14),190(16),117(13),69(18),58(100);Micronesiantunicateanditspredator,
aprosobranchmolluskChelynotussemperi28
KuanoniamineB(28)
2 Yellowamorphouspowder;mp>300(cid:3)C;UV(MeOH)k (loge):204(4.24),240
N1 3 (4.32),264(4.18),294(sh,3.89),344(3.87),360(3.87),450m(3a.x44)nm;UV(MeOH+)k
2 max
N 12a 12b 3a3b 4 5 (loge):204(4.17),238(4.21),270(4.08),306(4.27),344(3.65),360(3.73),530(3.41)nm;
11 S 9a 9 8a12cNH8 7a 7 6 MIRH(zC)H:dCHl38).6m9ma(xd:,3J6=20,5.1064H0z,,1H45-20),,172.7220,(d1,1J10=,150.400Hczm,(cid:1)H1-;31)H,8.N09M(dR,J(D=M7S.O8-Hd6z,,H30-04),
28 13 7.05(ddd,J=7.8,7.2,0.6Hz,H-5),7.51(dd,J=8.1,7.2Hz,H-6),7.45(dd,J=8.1,
14 0.6Hz,H-7),10.25(s,H-8),9.09(s,H-11),3.10(t,J=7.2Hz,H-13),3.34(td,J=7.2,
HN1516 17 18 19 5.2Hz,H-14),8.40(t,J=5.2Hz,H-15),2.00(m,H-17),2.00(m,H-18),0.83(d,
J=7.0Hz,H-19,20);13CNMR(DMSO-d,75MHz):d 150.70(C-2),108.26(C-3),
O 6 C
139.13(C-3a),115.61(C-3b),123.66(C-4),120.80(C-5),131.57(C-6),116.14(C-7),
20
139.17(C-7a),133.39(C-8a),104.37(C-9),139.70(C-9a),148.50(C-11),140.59(C-12a),
143.42(C-12b),117.58(C-12c),30.94(C-13),36.39(C-14),172.91(C-16),44.44(C-17),
25.17(C-18),22.01(C-19,20);HREIMSm/z:402.1520(calcdforC H NOS402.1526);
23 22 4
EIMSm/z(rel.int.):402(19),314(20),301(21),289(72),261(78),234(23),190(22);
Micronesiantunicateanditspredator,aprosobranchmolluskChelynotussemperi28
(continuedonnextpage)
114 S.R.M. Ibrahim, G.A.Mohamed
Table2(continued)
DehydrokuanoniamineB(29)
N1 2 3 4O5r2an(6g0e4s7o)lindm;U;UVV(M(MeOeHOH)k,mTaFxA(e)):k237((5e0):,926777),(24631,6(4300),1226071,(32404,7(2106),,41330)6,(34509,3(3136),9,5335)9,
max
N 12a 12b 3a3b 4 5 (11,447),527(5940)nm;IR(film)mmax:3284,3186,3151,3129,3071,3058,3036,3026,
11 S 9a 9 8a12cNH8 7a 7 6 (2d9,2J1,=2865.15,1H6z4,1H,1-623),27,.185767(d,,14J5=2c6m.5(cid:1)Hl;1zH,HN-M3),R8.(2D7M(dS,OJ-d=6-T8.F2AH-zd,,5H0-04)M,7H.2z7):(ddHdd8.,46
29 13 J=8.2,5.3,2.1Hz,H-5),7.72(m,H-6),7.72(m,H-7),11.71(brs,H-8),9.43(s,H-11),
14 3.12(t,J=7.3Hz,H-13),3.31(td,J=7.3,5.3Hz,H-14),8.35(t,J=5.3Hz,H-15),
HN1516 17 18 19 5.63(septet,J=1.1Hz,H-17),2.15(d,J=1.1Hz,H-19),1.79(d,J=1.1Hz,H-20);
13CNMR(DMSO-d-TFA-d,125MHz):d 142.72(C-2),107.57(C-3),148.50(C-3a),
O 6 C
20 114.13(C-3b),125.53(C-4),122.98(C-5),135.30(C-6),117.5(C-7),140.48(C-7a),132.80
(C-8a),108.44(C-9),143.15(C-9a),153.83(C-11),132.74(C-12a),131.80(C-12b),118.25
(C-12c),30.98(C-13),36.19(C-14),167.84(C-16),118.08(C-17),150.30(C-18),19.50(C-
19),26.84(C-20);FABMS(glycerol)m/z:401[M+H]+,302,288;HRFABMS(glycerol)
m/z:401.1429[M+H]+(calcdforC H NOS401.1436);FijianascidianCystodytes
23 21 4
sp.35
KuanoniamineC(30)
1 2 Yellowamorphouspowder;mp>300(cid:3)C;UV(MeOH)kmax(loge):206(4.24),240
N 3 (4.32),264(4.20),294(sh,3.90),344(3.88),359(3.86),450(3.30)nm;UV(MeOH,H+)
N 12a 12b 3a3b 4 5 kmax(loge):206(4.16),240(4.22),270(4.07),306(4.27),360(3.75),526(3.40)nm;IR
11 S 9a 9 8a12cNH8 7a 7 6 M(CHHzC):l3d)Hmm8a.6x:83(5d8,0J,=31550.0,1H6z4,5H,1-25)9,07,.71137(0d,,1J3=10,5.101H40z,cHm-(cid:1)31);,18H.08N(Md,RJ=(DM7.7SOH-zd,6H,3-40)0,
30 13 7.05(dt,J=7.7,4.0Hz,H-5),7.43(d,J=4.0Hz,H-6),7.43(d,J=4.0Hz,H-7),10.10
14 (s,H-8),9.07(s,H-11),3.08(t,J=7.2Hz,H-13),3.30(td,J=7.2,5.2,H-14),8.27(t,
HN1516 17 J=5.2Hz,H-15),2.06(q,J=7.2Hz,H-17),0.96(t,J=7.2Hz,H-18);13CNMR
18 (DMSO-d,100MHz,):d 143.0(C-2),108.2(C-3),139.4(C-3a),114.3(C-3b),125.4(C-
O 6 C
4),122.8(C-5),135.0(C-6),117.6(C-7),140.4(C-7a),133.5(C-8a),107.7(C-9),140.2(C-
9a),153.2(C-11),140.7(C-12a),143.5(C-12b),118.3(C-12c),36.3(C-13),30.9(C-14),
174.6(C-15),28.4(C-16),9.7(C-17);HREIMSm/z:374.1270(calcdforC H NOS
21 18 4
374.1339),289.0311(calcdforC HNOS289.0313);EIMSm/z(re.int.):374(5%),370
16 7 3
(10),313(15),299(46),289(52),278(47),261(61),234(11),190(13),169(12),149(49),
86(77),69(100);Micronesiantunicateanditspredator,aprosobranchmollusk
ChelynotussemperiandIndonesianspongeOceanapiasp.21,23,42
KuanoniamineD(31)
2 Yellowamorphouspowder;mp>300(cid:3)C;UV(MeOH)k (loge):206(4.24),240
N 3 (4.32),264(4.20),344(3.88),358(3.87),452(3.38)nm;UVm(aMxeOH,H+)k (loge):206
max
N 12a 12b 3a3b 4 5 (4.15),240(4.22),270(4.07),306(4.27),360(3.75),526(3.39);IR(CHCl3)mmax:3610,
11 12c 3000,2940,2840,1640,1590,1460,1240,1210,1100,1060,1000cm(cid:1)1;1HNMR
S 9a 9 8a NH 7a 7 6 (DMSO-d6,300MHz):dH8.70(d,J=5.1Hz,H-2),7.73(d,J=5.1Hz,H-3),8.11(d,
31 13 J=8.1Hz,H-4),7.06(dt,J=8.1,3.9Hz,H-5),7.45(d,J=3.9Hz,H-6),7.45(d,
14 J=3.9Hz,H-7),10.15(s,H-8),9.09(s,H-11),3.07(t,J=7.2Hz,H-13),3.27(td,
HN1516 17 J=7.2,5.2,H-14),8.39(t,J=5.2Hz,H-15),1.87(s,H-17);13CNMR(DMSO-d6,75
MHz):d 151.01(C-2),108.57(C-3),139.33(C-3a),115.78(C-3b),124.01(C-4),121.07
O C
(C-5),131.92(C-6),116.34(C-7),139.33(C-7a),133.49(C-8a),104.56(C-9),139.59(C-
9a),149.01(C-11),139.86(C-12a),143.56(C-12b),117.74(C-12c),31.08(C-13),36.74(C-
14),170.96(C-16),22.52(C-17);HREIMSm/z:360.1007(calcdforC H NOS
20 16 4
360.1045),288.0590(calcdforC H NS288.0595);EIMSm/z:360(40),356(18),314
17 10 3
(26),301(31),299(30),288(100);Micronesiantunicateanditspredator,aprosobranch
molluskChelynotussemperi28
N-DeacetylkuanoniamineC(32)
2 Orangeamorphouspowder;UV(MeOH)k (loge):201(4.14),239(4.33),264(4.11),
N 3 295(4.08),304(4.05),342(3.82),355(3.85)nmmax;1HNMR(DMSO,300MHz):d 8.67(d,
H
11 N 12a 12b12c 3a3b 4 5 J7.=405(m.1,HHz-,6H,7-)2,),9.70.868(s(,dH,J-1=1),53..10H8(zb,rH,H-3-)1,38).,026.9(d5,(Jbr=,H7-.194H);z1,3CH-N4)M,7R.02(D(mM,SHO-,54)0,0
S 93a29 138a NH 7a 7 6 M13H1.8z):(Cd-C6)1,5101.96.(3C(-C2)-,7)1,0183.49.(6C(-C3-)7,a1)3,91.433(.C8-(3Ca-)8,a1)1,51.806(.C0-(3Cb-)9,)1,2134.09.0(C(-C4-)9,a1)2,01.488(.C9-(5C),-
14 11),140.7(C-12a),143.5(C-12b),117.9(C-12c),34.6(C-13),39.6(C-14);ESIMSm/z:319
NH2 [M+H]+;ESIMS/MSm/z:302[319-NH3]+;HREIMSm/z:318.0930(calcdfor
C H NS318.0939);TheMicronesianspongeOceanapiasp.23
18 14 4
Pyridoacridine alkaloids from deep-water marineorganisms 115
Table2(continued)
KuanoniamineF(33)
N1 2 3 2Y6e2ll(o4w.2g9u),m2;9[6a](Dsh+,31.9085)(,c304.618(4,.C04H),3O36H3)(;4U.0V5)(,M45e5O(H3.)3k8m)anxm(l;oIgRe)(:K2B06r)(m4.26:),3224721,(42.94696),,
max
N 12a 12b 3a3b 4 5 1647,1573,1469,1413,1260,831,758cm(cid:1)1;1HNMR(CDCl3,500MHz):dH8.81(d,
11 12c J=4.7Hz,H-2),7.50(d,J=4.7Hz,H-3),7.93(d,J=8.0Hz,H-4),7.05(t,
S 9a 9 8a NH8 7a 7 6 J=7.5Hz,H-5),7.42(t,J=7.5Hz,H-6),7.50(brd,J=6.6Hz,H-7),10.20(brs,H-8),
33 13 18 8.77(s,H-11),3.13(dd,J=6.8,5.2Hz,H-13),3.42(dd,J=6.8,5.2Hz,H-14),6.22
14 (brs,H-15),2.26(dd,J=13.8,6.9Hz,H-17),1.24(d,J=6.9Hz,H-18),1.78(dd,
HN1516 20 J=13.8,7.4Hz,H-19),1.56(dd,J=13.8,7.4Hz,H-19),0.98(t,J=7.4Hz,H-20);1H
17 19 NMR(DMSO-d,500MHz):d 8.70(d,J=4.8Hz,H-2),7.72(d,J=4.8Hz,H-3),
O 6 H
8.10(d,J=7.9Hz,H-4),7.06(brt,J=5.2Hz,H-5),7.46(brt,J=5.2Hz,H-6),7.49
(brt,J=5.2Hz,H-7),10.24(brs,H-8),9.11(s,H-11),3.36(t,J=7.2Hz,H-14),3.09
(brt,J=7.2Hz,H-13),8.38(brs,H-15),2.16(ddd,J=13.8,6.9Hz,H-17),0.99(d,
J=6.9Hz,H-18),1.52(dd,J=7.4,6.9Hz,H-19),1.31(dd,J=7.4,6.9Hz,H-19),
0.76(t,J=7.4Hz,H-20);13CNMR(DMSO-d,125MHz):d 150.6(C-2),108.2(C-3),
6 H
139.3(C-3a),115.7(C-3b),123.7(C-4),120.7(C-5),131.5(C-6),116.0(C-7),139.7(C-7a),
133.3(C-8a),104.5(C-9),139.3(C-9a),148.6(C-11),140.5(C-12a),143.4(C-12b),117.6
(C-12c),30.9(C-13),36.2(C-14),176.8(C-16),41.1(C-17),17.1(C-18),26.5(C-19),11.5
(C-20);(+)-ESIMSm/z:403[M+H]+,401[M-H]+;(+)-HRESIMSm/z:403.1598
(calcdforC H NOS403.1593);Singaporeanascidian43
23 23 4
DehydrokuanoniamineF(34)
1 2 N3 (P4u.3rp),le52o8il;(3U.2V)n(mM;eIORH(,RHB+r))mkma:x3(3lo1g0,e3):023209,2(942.01),,1266583,(31.492)4,3c0m7(cid:1)(14;.12H),N31M7.7R((4D.3M),S3O58-
10 11 11a 11b11c3a 4 N3` d6,400MHz):dH7.85(m,H-1m)a,x8.55(m,H-2),11.24(brs,H-7),7.68(m,H-8),7.68(m,
2` H-9),7.23(m,H-10),8.26(d,J=8.4Hz,H-11),3.15(t,J=7.1Hz,H-12),3.39(H-13),
9 7a N7 6a 5 S 8.30(t,J=5.1Hz,H-14),6.38(q,J=6.2Hz,H-17),1.68(d,J=6.2Hz,H-18),1.72(s,
8 H 6 H-19),9.35(s,H-20);13CNMR(DMSO-d,100MHz):d 107.9(C-1),144.8(C-2),135.3
34 12 6 C
13 (C-4),144.0(C-5),107.4(C-6),133.0(C-6a),140.3(C-7a),117.3(C-8),134.4(C-9),122.5
HN 15 O (C-10),127.1(C-11),114.6(C-11a),152.4(C-11b),118.2(C-11c),31.0(C-12),36.8(C-13),
14 169.6(C-15),131.0(C-16),130.7(C-17),13.7(C-18),12.4(C-19),151.0(C-20);ESIMSm/
16 18 z:401[M+H]+;HRESIMSm/z:401.1448[M+H]+(calcdforC H NOS,401.1436);
19 17 South-PacificOceanascidianCystodytesviolatinctus42 23 20 4
Sagitol(35)
N 2 3 Orangeresidue;UV(MeOH)kmax:264,340nm;1HNMR(DMSO-d6,400MHz):dH8.87
N 12a 12b 3a3b 4 (d,J=5.8Hz,H-2),8.49(d,J=5.8Hz,H-3),8.72(d,J=7.8Hz,H-4),7.81(t,
12c 5 J=7.5Hz,H-5),7.97(t,J=7.8Hz,H-6),8.27(d,J=7.8Hz,H-7),9.29(s,H-11),2.90
11 SH9Oa 9 8a N 7a 7 6 (1m6),,H0.-7193A(t),,J2.=496(.m9,HHz-,1H3B-1)7,)2;.9133C(mN,MHR-14(DA)M,2S.O75-d(6m,,1H00-1M4BH)z,)1:.7d1C(1q5,0J.5=(C7-.23)H,1z1,6H.2-
13 (C-3),140.1(C-3a),122.3(C-3b),123.5(C-4),128.5(C-5),132.5(C-6),129.8(C-7),146.5
14
35 (C-7a),162.5(C-8a),72.8(C-9),146.1(C-9a),155.6(C-11),151.5(C-12b),115.1(C-12c),
HN 16
15 46.5(C-13),35.4(C-14),174.2(C-15),28.2(C-16),9.5(C-17);ESIMSm/z:391[M+H]+;
O 17 IndonesianspongeOceanapiasp.21
SagitolC(36)
2 Orangeresidue;UV(MeOH)k :254,366nm;1HNMR(DMSO-d,400MHz):d 9.15
N 3 max 6 H
(d,J=5.4Hz,H-2),8.92(d,J=5.4Hz,H-3),9.05(dd,J=8.2,1.3Hz,H-4),8.06(dt,
N 12a 12b 3a3b 4 5 J=8.2,1.3Hz,H-5),8.11(dt,J=8.2,1.3Hz,H-6),8.47(dd,J=8.2,1.3Hz,H-7),
12c
11 9.72(s,H-11),3.20(m,H-13),2.78(m,H-14),2.61(m,H-16),1.25(d,J=6.9Hz,H-17),
SHO9a 9 8a N 7a 7 6 1.25(d,J=6.9Hz,H-18);13CNMR(DMSO-d6,100MHz):dC149.1(C-2),117.2(C-3),
13 140.5(C-3a),122.5(C-3b),124.0(C-4),131.6(C-5),131.8(C-6),132.0(C-7),146.5(C-7a),
36 14 18 162.7(C-8a),72.5(C-9),146.3(C-9a),162.1(C-11),149.0(C-12a),152.0(C-12b),115.5
HN 15 16 (C-12c),47.2(C-13),41.5(C-14),174.3(C-15),39.9(C-16),26.3(C-17),26.3(C-18);
17 HRESIMSm/z405.1464[M+H]+(calcdforC H NOS,405.1463);Indonesian
O 22 21 4 2
spongeOceanapiasp.21
(continuedonnextpage)
116 S.R.M. Ibrahim, G.A.Mohamed
Table2(continued)
Petrosamine(37)
Br Darkblueneedles;mp330(cid:3)C;UV(MeOH)k (e):286(36,418),346(11,732),369
max
2 (11,183),414(6161)nm;IR(film)mmax:3056,1644,1583,1531,1494,1422,924,
1 3 838cm(cid:1)1;1HNMR(DMSO-d ,300MHz):d 8.37(d,J=2.0Hz,H-1),7.92(dd,
6 H
Keto-form 4 J=9.2,2.0Hz,H-3),9.16(d,J=9.2Hz,H-4),4.75(s,H-6),9.88(s,H-9),9.17(d,
N
4a J=5.3Hz,H-11),9.29(d,J=5.3Hz,H-12),4.60(s,H-14),3.83(s,H-15,16);13C
11 12 12a 12b 12c4b5 O NMR(DMSO-d6,75MHz):dC131.8(C-1),122.9(C-2),135.1(C-3),126.3(C-4),120.0
H3C N 8a 8 7a N 6 (1C45-4.6a)(,C1-298),.814(C2.-54b()C,-11817),.212(C1.-75)(,C6-91.28),(C13-61).5,1(1C4-.122(aC),-71a4)1,.416(1C.-31(2Cb-)8,)1,1143.39.(9C(-C1-28ca),),
14 9 OH3C CH3 142.1(C-13a),48.3(C-14),53.1(C-15,16);HRFABMSm/z:422.0505[M+H]+(calcd
Br forC H O N Br422.0504);ThaimarinespongePetrosian.sp.44
37 2 21 17 2 3
1 3
Enol-form N 4
4a
11 12 12a 12b 12c4b5 OH
N
H134C 9 8a O8 H73aCN CH63
Debromopetrosaminetrifluoroacetatesalt(38)
2 Purple-blueamorphoussolid;UV(MeOH)k (loge):216(4.49),282(4.74),374(3.38),
max
1 3 592(3.15)nm;IR(film)m :3063,1682,1648,1588,1498,1206,1129,801,722cm(cid:1)1;1H
max
1N313a 4 NMR(DMSO-d6,500MHz):dH8.19(d,J=9.0Hz,H-1),7.73(dd,J=9.0,7.5Hz,H-
11 12 12a 12b 44ab5 O 28).7,57.(8d4,(Jd=d,J6.=5H8z.0,,H7-.151H),z9,.3H9-3(d),,9J.2=7(6d.5,JH=z,H8.-01H2)z,,4H.5-34()s,,4H.4-114(s),,H3.8-64),(s9,.7H2-1(s5,),H3-.98)4,
12c
H3C N 9 8a 8 7a N 6 ((Cs,-H4)-,1162);51.23C(CN-4Ma)R,1(D15M.8S(OC--4db6,),121587M.2H(Cz)-:5d),C7114.34.0(C(C-6-)1,)1,1152.81.4(C(C-7-a2)),,116313..05((CC--83)),,113225..71
14 38 OH3C CH3 (C-8a),145.9(C-9),142.0(C-11),122.9(C-12),143.5(C-12a),139.5(C-12b),129.9(C-
16 15
12c),143.1(C-13a),49.0(C-14),54.1(C-15),54.1(C-16);HRESIMSm/z344.1415[M
+H]+(calcdforC H NO 344.1399);SpongeXestospongiacf.carbonaria45
21 18 3 2
EcionineA(39)
O Lightbrownsolid;UV(MeOH)k (loge):215(4.23),228(4.26),284(4.00),319(3.70),
max
O NH 376(3.80),443(3.28)nm;IR(KBr)m :1666,1462,1201,1136cm(cid:1)1;1HNMR(DMSO-
10 9 8a 8 7a HNO 6 CF3 dJ6=,5070.8,M7H.2zH):zd,HH8-3.4)1,9(.d0,7J(d=,J7.=8H7mz.a8,xHH-z1,)H,8-4.1)7,9(.d1d6,(Jd,=J7=.8,5.74.2HHz,z,HH-5-)2,),9.82.809(d(d,d,
11 12a 12b 5 J=5.4Hz,H-6),10.83(s,H-7),11.12(s,8-NH),2.92(t,J=7.8Hz,H-10),4.11(dd,
NH 12c 4b J=7.8,7.2Hz,H-11),11.57(brs,H-12);13CNMR(DMSO-d,125MHz):d 131.1(C-
12 N 13a 4a 4 1),132.9(C-2),131.6(C-3),124.7(C-4),122.8(C-4a),136.8(C-46b),121.3(C-5)C,149.5(C-
39
6),142.5(C-7a),157.7(C-8),99.0(C-8a),193.2(C-9),34.6(C-10),40.5(C-11),157.9(C-
1 3
2 12a),142.0(C-12b),116.2(C-12c),144.1(C-13a);(+)-LRESIMSm/z(rel.int.):301
[M(cid:1)CFCOO(cid:1)]+(100);(+)-HRESIMSm/z:301.1079[M-CFCOO(cid:1)]+(calcdfor
3 3
C H NO301.1084);AustralianmarinespongeEcionemiageodides16
18 13 4
EcionineB(40)
O Lightbrownsolid;UV(MeOH)k (loge):211(3.66),235(3.74),286(3.48),321(3.20),
max
O NH HO CF3 3(38.240()3,.2306)6,(434.078()3,.40301);(U2.V97)(,M5e4O1H(2.+77)KnOmH;)IRkm(aKxB(lro)gme)::231421(03,.9176)7,42,41154(73,.7134)3,22,913203,
9 8 N max
10 8a 7a 6 1135,1025,994cm(cid:1)1;1HNMR(DMSO-d6,500MHz):dH10.61(s,1-OH),7.51(d,
11 NH12a 12b 12c 4b 5 JJ==75..84HHzz,,HH--25)),,79..9266((ddd,,JJ==5.84.4H,z7,.8HH-6z),,H10-3.8)6,8(.s4,6H(-d7,),J1=1.180.4(sH,z8,-NHH-4)),,29..9058((td,,
12 N 13a 4a J=7.8Hz,H-10),4.20(dt,J=7.8,7.8Hz,H-11),11.61(s,H-12);13CNMR(DMSO-
40 4 d,125MHz):d 155.8(C-1),115.1(C-2),133.2(C-3),114.6(C-4),123.6(C-4a),136.9
1 3 6 C
HO (C-4b),121.6(C-5),149.4(C-6),142.6(C-7a),157.6(C-8),98.9(C-8a),193.4(C-9),34.5
2
(C-10),39.9(C-11),157.7(C-12a),139.2(C-12b),116.4(C-12c),133.5(C-13a);(+)-
LRESIMSm/z(rel.int.):317[M(cid:1)CFCOO(cid:1)]+(100);(+)-HRESIMSm/z:317.1039
3
[M(cid:1)CFCOO(cid:1)]+(calcdforC H NO 317.1033);AustralianmarinespongeEcionemia
3 18 13 4 2
geodides16