Transformation of tricyclic makaluvamines from the marine sponge Zyzzya fuliginosa into damirones

Article abstract of DOI:10.1023/A:1022489508349

Makaluvamines H and C isolated from the marine sponge Zyzzya fuliginosa were transformed into damirones A and B, respectively, by alkaline hydrolysis. The crystal structure of damirone A was established by X-ray diffraction analysis.

Full text of DOI:10.1023/A:1022489508349

258
Russian Chemical Bulletin, International Edition, Vol. 52, No. 1, pp. 258—260, January, 2003
Transformation of tricyclic makaluvamines
from the marine sponge Zyzzya fuliginosa into damirones
N. K. Utkina,aꢀ A. V. Gerasimenko, and D. Yu. Popovb
b
aPacific Institute of Bioorganic Chemistry of the FarꢀEastern Branch of the Russian Academy of Sciences,
1
59 prosp. 100ꢀletiya Vladivostoka, 690022 Vladivostok, Russian Federation.
Fax: +7 (423 2) 31 4050. Eꢀmail: utkinan@mail.ru
b
Institute of Chemistry of the FarꢀEastern Branch of the Russian Academy of Sciences,
59 prosp. 100ꢀletya Vladivostoka, 690022 Vladivostok, Russian Federation
1
Makaluvamines H and C isolated from the marine sponge Zyzzya fuliginosa were transꢀ
formed into damirones A and B, respectively, by alkaline hydrolysis. The crystal structure of
damirone A was established by Xꢀray diffraction analysis.
Key words: marine sponge, Zyzzya fuliginosa; marine alkaloids; makaluvamines; damirones;
alkaline hydrolysis; crystal and molecular structure, Xꢀray diffraction analysis.
A
series of alkaloids based on the pyrroꢀ
lo[4,3,2ꢀde]quinoline ring system were isolated from difꢀ
ferent marine sponges. This series of metabolites includes
1
—6
7,8
batzellines,9 isoꢀ
discorhabdins,
prianosins,
1
0
11—13
damirones,13,14
batzellines,
makaluvamines,
veiutamine,1 and epinardins. Makaluvamines A—M
5
16
and damirones A—C were isolated from sponges of the
1
7
genus Zyzzya (order Poecilosclerida, family Iophonidae).
Tricyclic makaluvamines A—C, H, and I and damirones
A—C are the simplest of this alkaloid series. When studyꢀ
ing aromatic marine sponge metabolites, we isolated
makaluvamines C, E, G, and H and damirones A and B
from the Australian marine sponge Zyzzya fuliginosa
yield. It should be noted that the replacement of the amino
group in isobatzelline A (5) by the oxygen atom proceeds
through the diazonium salt to give batzelline A (6) in low
10
yield. The mass spectrum and melting point of comꢀ
(
Carter, 1879).18 A comparison of the compositions of
pound 3 are identical with those of natural damirone A.
ethanolic extracts of fresh and lyophilized sponges reꢀ
vealed that makaluvamines H (1) and C (2) prevailed in
extracts from the fresh sponge, whereas damirones A (3)
and B (4) were dominant in extracts from the lyophilized
sponges. In our opinion, makaluvamines 1 and 2 were
transformed into damirones 3 and 4, respectively. In the
present study, we demonstrated for the first time that this
transformation proceeds readily under alkaline conditions.
1
Since the H NMR spectra of compound 3 and natural
damirone A measured in MeOHꢀd differ only slightly,
4
compound 3 was recrystallized to obtain crystals suitable
for Xꢀray study. Xꢀray diffraction analysis confirmed the
structure of semisynthetic damirone A (3) and revealed
that the tricyclic system of 3 is virtually planar and is
similar to the tricyclic system of batzelline A (6).9
Compound 2 was also treated with an aqueous alkali,
which gave rise to compound 4. The spectral and physiꢀ
cochemical characteristics of this compound are identical
with those of natural damirone B. No melting point deꢀ
pression was observed for a mixed sample of both comꢀ
pounds.
Under the conditions of alkaline hydrolysis, comꢀ
pounds 1 and 2, apparently, lose one proton to form
оꢀiminoquinones, which are readily hydrolyzed to give
оꢀquinones 3 and 4, respectively. The transformation of
the pꢀiminoquinoid system of makaluvamines 1 and 2
into the oꢀquinoid system of compounds 3 and 4, respecꢀ
tively, leads to a considerable decrease in cytotoxicity
R = Me (1, 3), H (2, 4)
Treatment of compound 1 with an aqueous solution of
NaOH at room temperature afforded compound 3 in high
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 246—248, January, 2003.
066ꢀ5285/03/5201ꢀ258 $25.00 © 2003 Plenum Publishing Corporation
1

Transformation of makaluvamines into damirones
O(1)
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
259
Synthesis of damirone A (3) from makaluvamine H (1). A
mixture of compound 1 (10 mg), CHCl (5 mL), and 0.5 M
3
C(12)
aqueous NaOH (2 mL) was kept at ∼ 20 °C for 10 min. Then the
reaction mixture was extracted with CHCl3 (2×15 mL). The
combined organic extracts were washed with water (2×5 mL)
and dried with Na SO . After evaporation of the solvent, the
O(2)
C(6)
N(2)
C(5)
2
4
residue was chromatographed on Sephadex LHꢀ20 using the
C(7)
CHCl —MeOH solvent system (4 : 1). Damirone 3 was obꢀ
3
C(4)
tained in a yield of 7.4 mg (86%), m.p. 240—242 °C (CHCl )
3
1
4
1
(
cf. lit. data : 240—242 °C). H NMR (MeOHꢀd ), δ: 2.78 (t,
4
C(10)
C(8)
2
H, H(3), J = 7.0 Hz); 3.07 (s, 3 H, N(5)Me); 3.59 (t, 2 H,
H(4), J = 7.0 Hz); 3.90 (s, 3 H, N(1)Me); 5.29 (s, 1 H, H(6));
C(3)
C(2)
1
6
7
3
.62 (s, 1 H, H(2)). H NMR (CDCl ), δ: 2.85 (t, 2 H, H(3), J =
.0 Hz); 3.06 (s, 3 H, N(5)Me); 3.57 (t, 2 H, H(4), J = 7.0 Hz);
3
C(9)
N(1)
.93 (s, 3 H, N(1)Me); 5.29 (s, 1 H, H(6)); 6.62 (s, 1 H, H(2)).
+
MS, m/z: 216 [M ].
Synthesis of damirone B (4) from makaluvamine C (2). Analoꢀ
gous treatment of compound 2 (5 mg) afforded compound 4
1
4
C(1)
(3.5 mg, 70%), m.p. >250 °C (MeOH) (cf. lit. data : m.p.
250 °C). The melting point of a mixed sample with natural
C(11)
>
1
damirone B was higher than 250 °C. H NMR (DMSOꢀd ), δ:
6
2
.78 (t, 2 H, H(3), J = 7.5 Hz); 3.03 (s, 3 H, NMe); 3.58 (t, 2 H,
Fig. 1. Structure of molecule 3.
H(4), J = 7.5 Hz); 5.14 (s, 1 H, H(6)); 7.09 (s, 1 H, H(2)); 12.42
+
(
s, 1 H, NH). MS, m/z: 202 [M ].
against Ehrlich carcinoma cells. Thus ID for compounds
Crystallographic data for compound 3. C12H12N O ,
50
2
2
–
1
1
and 3 are 12.5 and 46.5 µg mL and for compounds 2
M = 216.24; crystals are orthorhombic, space group Pbca;
a = 7.3233(8), b = 15.903(2), c = 17.112(2) Å; α = 90, β = 90,
and 4 are 26.5 and 50 µg mL 1, respectively.
–
3
–3
γ = 90°; V = 1992.9(4) Å , Z = 8, d
= 1.44 g cm
,
calc
F(000) = 912.
Experimental
Crystals of 3 were grown from a solution in CHCl by slow
3
evaporation of the solvent. The Xꢀray diffraction data were colꢀ
lected from a prismatic crystal (0.36×0.23×0.12 mm) on a fourꢀ
circle Bruker SMART CCD diffractometer (MoꢀKα radiation,
λ = 0.71073 Å, graphite monochromator, ω scan technique) at
1
The H NMR spectra were recorded on a Bruker AVANCE
DPXꢀ300 spectrometer with SiMe as the internal standard. The
4
mass spectra were measured on an LKBꢀ9000S mass spectromꢀ
eter with direct inlet of the sample into the ion source; the
ionizing voltage was 70 eV.
The isolation and identification of the compounds from the
marine sponge Z. fuliginosa have been described earlier.
1
9
∼ 21 °C with the use of the SMART and SAINTꢀPlus programs.
A total of 1762 independent reflections were measured of which
1315 reflections with I > 2σ(I ) were used in the refinement. The
structure was solved by direct methods and refined anisotropiꢀ
1
8
Table 1. Bond length (d) and bond angles (ω) in compound 3
Bond
d/Å
Angle
ω/deg
Angle
ω/deg
O(1)—C(6)
O(2)—C(7)
N(1)—C(9)
N(1)—C(11)
N(1)—C(1)
N(2)—C(4)
N(2)—C(5)
N(2)—C(12)
C(1)—C(2)
C(2)—C(3)
C(3)—C(4)
C(3)—C(10)
C(5)—C(10)
C(5)—C(6)
C(6)—C(7)
C(7)—C(8)
C(8)—C(9)
C(9)—C(10)
1.223(1)
1.236(2)
1.344(2)
1.462(2)
1.474(2)
1.364(2)
1.376(2)
1.465(2)
1.526(2)
1.497(2)
1.380(2)
1.388(2)
1.379(2)
1.437(2)
1.563(2)
1.415(2)
1.380(2)
1.449(2)
C(9)—N(1)—C(11)
C(9)—N(1)—C(1)
C(11)—N(1)—C(1)
C(4)—N(2)—C(5)
C(4)—N(2)—C(12)
C(5)—N(2)—C(12)
N(1)—C(1)—C(2)
C(3)—C(2)—C(1)
C(4)—C(3)—C(10)
C(4)—C(3)—C(2)
C(10)—C(3)—C(2)
N(2)—C(4)—C(3)
N(2)—C(5)—C(10)
N(2)—C(5)—C(6)
119.5(1)
120.9(1)
116.6(1)
108.8(1)
125.7(1)
125.5(1)
115.1(1)
109.3(1)
105.8(1)
136.0(1)
118.2(1)
109.2(1)
106.5(1)
131.4(1)
C(10)—C(5)—C(6)
O(1)—C(6)—C(5)
O(1)—C(6)—C(7)
C(5)—C(6)—C(7)
O(2)—C(7)—C(8)
O(2)—C(7)—C(6)
C(8)—C(7)—C(6)
C(9)—C(8)—C(7)
N(1)—C(9)—C(8)
N(1)—C(9)—C(10)
C(8)—C(9)—C(10)
C(5)—C(10)—C(3)
C(5)—C(10)—C(9)
C(3)—C(10)—C(9)
121.9(1)
126.4(1)
119.7(1)
113.9(1)
123.8(1)
116.0(1)
120.2(1)
122.2(1)
127.6(1)
114.6(1)
117.8(1)
109.7(1)
123.8(1)
126.6(1)

260
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
Utkina et al.
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2
2
2
weighting scheme w = 1/[σ (F ) + (0.0733P) ], where P =
o
2
2
(
Fo + 2F )/3. All calculations were carried out with the use of
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were placed in geometrically calculated positions and refined
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c
2
0
2
2
are given in Table 1.
1
2. J. R. Carney, P. J. Scheuer, and M. KellyꢀBorges, Tetraꢀ
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Received February 1, 2002;
in revised form September 30, 2002