Ecteinascidins 770 and 786 from the Thai tunicate Ecteinascidia thurstoni

Article abstract of DOI:10.1021/np010485k

Ecteinascidins 770 (1b) and 786 (3b) were isolated from the pretreated Thai tunicate Ecteinascidia thurstoni with potassium cyanide in buffer solution (pH 7). These structures were fully elucidated by extensive 2D NMR analysis.

Full text of DOI:10.1021/np010485k

J . Nat. Prod. 2002, 65, 935-937
935
Ectein a scid in s 770 a n d 786 fr om th e Th a i Tu n ica te Ectein a scid ia th u r ston i
,
†
†
†
†
Khanit Suwanborirux,* Kornvika Charupant, Surattana Amnuoypol, Sunibhond Pummangura,
‡
,‡
Akinori Kubo, and Naoki Saito*
Faculty of Pharmaceutical Sciences, Chulalongkorn University, Phyathai Road, Bangkok 10330, Thailand, and
Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, J apan
Received October 3, 2001
Ecteinascidins 770 (1b) and 786 (3b) were isolated from the pretreated Thai tunicate Ecteinascidia
thurstoni with potassium cyanide in buffer solution (pH 7). These structures were fully elucidated by
extensive 2D NMR analysis.
Ecteinascidin 743 (1a ) is a novel marine natural product
obtained from the Caribbean tunicate Ecteinascidia tur-
binata, which was discovered along with ecteinascidin 729
1
(
2) and related compounds (Figure 1). Among this group,
2
is generally the most cytotoxic compound, and it was
initially planned that 2 would advance to clinical trials.
The choice was switched to 1a , however, due to its greater
abundance in the tunicate. Now, 1a is undergoing phase
2
II clinical trials for cancer therapy. The combination of
unique structural features and the high degree of func-
tionalization of 1a presents a formidable challenge to the
synthetic chemist. The first elegant total synthesis of 1a
and an improvement of the original synthesis were de-
3
scribed by Corey and co-workers. In addition, an efficient
process for the preparation of 1a starting from cyanosa-
fracin B, which is readily prepared from microbial safracin
B, was recently described by the Pharma Mar Laboratories
4
group. With an aim to elucidate the structure-activity
relationships, Corey, Schreiber, and co-workers discovered
phthalascidin, which is easily made from a synthetic
intermediate and is considerably more stable in solution
than 1a .5
F igu r e 1.
,6
As a part of our search for new anticancer metabolites
in the isolation and characterization of biologically active
compounds from Thai marine animals, we found a Thai
tunicate, Ecteinascidia thurstoni Herdman 1891, which is
the first example of the Asian tunicate contained this class
of molecules, growing around Phuket Island. We now report
the isolation and structural elucidation of ecteinascidin 770
achieved, and then potassium cyanide solution was added
and the mixture was allowed to stand for 5 h and was
further macerated with methanol. The extract was evapo-
rated to an aqueous emulsion, which was partitioned with
ethyl acetate. The organic layer was evaporated to dryness
and then partitioned again between methanol and hexane.
The methanol layer extract was concentrated, and the
residue was further separated by chromatography on a
Sephadex LH-20 column to afford a pale yellow solid. The
pale yellow solid was subjected to chromatography on a
silica gel column with 1:2 hexane-ethyl acetate to afford
(1b) and ecteinascidin 786 (3b) from the KCN-pretreated
Thai tunicate. Compound 1b was discovered in very small
amounts from the Caribbean tunicate, and ecteinascidin
7
7
86 (3b) is a derivative of ecteinascidin 759B (3a ).
-
4
The tunicate Ecteinascidia thurstoni was collected by
ecteinascidin 770 (1b, 225 mg, 6.0 × 10 % of wet weight).
scuba divers at Phuket Island at a depth of 1-5 m during
March and J uly 2000. Initial attempts to extract the
alkaloid were performed on 50 g of wet animal using the
Rinehart procedure, but there were only trace amounts of
alkaloid in the crude fraction. Natural products that have
an R-hydroxyamine functionality such as 1a are relatively
unstable during extraction. We attempted to stabilize 1a
by converting it to 1b by addition of potassium cyanide to
Further elution with 1:4 hexane-ethyl acetate afforded
-
4
ecteinascidin 786 (3b, 60 mg, 1.6 × 10 % of wet weight).
Ecteinascidin 770 (1b) was obtained as colorless prisms,
mp 216-218 °C (from methanol). High-resolution FABMS
of 1b demonstrated a molecular composition of C40
H
43
N
4
O
10
S
+
(M + H) by observation of the peak at a m/z 771.2693
1
(∆ -0.7 mmu) and the elemental analysis. The H chemical
shifts and proton coupling patterns of this compound were
identical with those reported by Rinehart and co-workers.
However, the lack of published data for 1b, particularly
8
the homogenized tunicate during workup. Phosphate
buffer solution was added to the homogenized samples of
frozen tunicate (38 kg, wet weight) until a pH of 7 was
1
3
C NMR data, frustrated our attempts to identify our
sample by simple comparison of NMR data.1b Therefore,
extensive analyses of spectral data were necessary to
confirm the structure. The IR spectrum of the KBr disk
had characteristic absorption bands such as 3530, 3500,
*
To whom correspondence should be addressed. Tel: +81-424-95-8794.
Fax: +81-424-95-8792. E-mail: naoki@my-pharm.ac.jp. Tel: +662-218-
8
363. Fax: +662-254-5195. E-mail: Khanit.S@chula.ac.th.
†
Chulalongkorn University.
Meiji Pharmaceutical University.
‡
-1
3350, 2930, 1770, 1740, and 1630 cm , but there was only
1
0.1021/np010485k CCC: $22.00
© 2002 American Chemical Society and American Society of Pharmacognosy
Published on Web 05/16/2002

9
36 J ournal of Natural Products, 2002, Vol. 65, No. 6
Notes
a very weak band of the cyano group in the region 2100-
east coast of Phuket Island at a depth of 1-5 m during March
and J uly 2000 and frozen until used. Freeze-dried animals (38
kg, wet weight) were homogenized in a blender with methanol.
Phosphate buffer solution was added to the resulting homo-
genized solution (40 L) to a pH of 7. Potassium cyanide (25 g)
was added, and the mixture was allowed to stand for 5 h.
Afterward the mixture was macerated with methanol (3 × 20
L). The extract was filtered, and the filtrate was concentrated.
The aqueous methanol extract (2 L) was partitioned by the
addition of ethyl acetate (8 L), and the solvent was removed
to obtain a residue (20 g), which was dissolved in methanol
(150 mL) and partitioned with hexane (600 mL). The methanol
extract was concentrated to give a residue (12 g), which was
successively chromatographed three times on Sephadex LH-
-
1 9
2
300 cm . To confirm the incorporation of a cyano group
at the C-21 position including the stereochemistry, HMBC,
HMQC, and NOESY experiments of 1b allowed for the
unambiguous assignment of almost all of the quaternary
carbons and confirmed the proposed structure. The 13
C
NMR spectral data of 1b and 1a revealed only two major
differences. The carbinolamine-containing carbon of 1b
(
C-21) shifted from 92.1 to 59.6 ppm, and an additional
1
0
carbon resonance was present at 118.2 ppm. The optical
rotation of 1b was -58.5 ° (c 1.0, CHCl
1
1,12
3
).
The new compound 3b was obtained as colorless prisms,
2
4
mp 197-199 °C (from methanol), and exhibited [R]
156.9° (c 0.6, CHCl ). Its structure was elucidated pre-
D
2
0 columns using chloroform-methanol (1:1), ethyl acetate,
-
3
and hexane-ethyl acetate (9:1) as the eluents to obtain a
mixture of ecteinascidins 770 and 786. This mixture was
further separated on a silica gel column using hexane-ethyl
acetate (1:2 to 1:4) as eluent to give ecteinascidins 770 (1b,
dominantly by interpretation of NMR and MS data and
comparison to spectral data for 1b. High-resolution FABMS
of 3b demonstrated the molecular composition of C40
43
H -
+
N
4
O
11S (M + H) by observation of the peak at m/z
2
25 mg) and 786 (3b, 60 mg).
7
87.2649 (∆ +0.3 mmu). Therefore, it might be the oxygen-
Ectein a scid in 770 (1b): colorless prisms from methanol,
mp 216-218 °C (dec); [R]24
-58.5 (c 1.0, CHCl
); CD ∆ꢀ nm
ated analogue of 1b. All protons and carbons were assigned
by extensive NMR measurements (including COSY, NOE-
SY, HMQC, and HMBC techniques). The major differences
D
3
(c 0.13 mmol/L, methanol, 24 °C) 0 (306), -12.0 (289), 0 (270),
1
+
12.8 (254), 0 (242), -51.0 (221), 0 (211), +39.4 (295); H NMR
(CDCl ) δ 6.60 (1H, s, 15-H), 6.46 (1H, s, 5′-H), 6.44 (1H, s,
′-H), 6.04 (1H, d, J ) 1.2 Hz, OCHO), 5.97 (1H, d, J ) 1.2
Hz, OCHO), 5.77 (1H, s, 18-OH), 5.59 (1H, br s, 6′-OH), 5.01
1H, d, J ) 11.6 Hz, 22-Hâ), 4.57 (1H, br s, 4-H), 4.32 (1H, br
s, 1-H), 4.28 (1H, dd, J ) 4.9, 1.2 Hz, 11-H), 4.18 (1H, d, J )
.8 Hz, 21-H), 4.12 (1H, dd, J ) 11.6, 2.0 Hz, 22-HR), 3.78
(3H, s, 17-OCH ), 3.60 (3H, s, 7′-OCH ), 3.51 (1H, d, J ) 4.9
in the 13C NMR spectral data of 3b, in comparison to those
of 1b, were in the downfield shifts of C-4 and a methylene
3
8
1
C-12′. Furthermore, the H NMR spectral data of 3b also
(
revealed the distinct upfield shift of H-4 and downfield shift
of H -12′, comparable to those of 1b. These observations
2
suggested that the sulfur atom between C-4 and C-12′
might be oxidized. An NOE between H-14â and H-21
revealed the relative stereochemistry at C-21. Thus, the
2
3
3
Hz, 3-H), 3.41 (1H, m, 13-H), 3.11 (1H, br t, 3′-HR), 2.91 (2H,
br d, J ) 7.6 Hz, 14-H ), 2.79 (1H, m, 3′-Hâ), 2.60 (1H, m,
′-Hâ), 2.42 (1H, dt, J ) 15.9, 3.4 Hz, 4′-HR), 2.35 (1H, br,
12′-H)*, 2.32 (3H, s, 16-CH ), 2.26 (3H, s, 5-OCOCH ), 2.19
), 2.15 (1H, m, 12′-H)*, 2.04 (3H, s, 6-CH
2
4
structure of ecteinascidin 786 was deduced to be ecteinas-
cidin 770 S-oxide.7
3
3
(
(
(
3H, s, 12-CH
* the signal overlapped with the methyl signal); C NMR
CDCl ) δ 172.6 (s, 11′-C), 168.2 (s, 5-OCOCH ), 147.9 (s, 18-
3
3
)
Isolation of marine natural products using this procedure
has the advantage of increasing the yield of labile ectein-
ascidin-type compounds. Actually, 1b was easily trans-
formed to 1a in high yield with silver nitrate,1 and the
transformation product was identical with authentic data
in all respects.
1
3
3
3
C), 145.3 (s, 7-C), 144.6 (s, 6′-C), 144.4 (s, 7′-C), 143.1 (s, 17-
C), 141.4 (s, 5-C), 140.2 (s, 8-C), 130.8 (s, 20-C), 129.4 (s, 16-
C), 129.2 (s, 10′-C), 125.8 (s, 9′-C), 121.2 (s, 10-C), 120.7 (d,
15-C), 118.4 (s, 19-C), 118.7 (s, 21-CN), 114.2 (d, 5′-C), 114.1
3
Compounds 1b and 3b have potent cytotoxic activity,
exhibiting IC50 values of 2.5 and 7.6 nM against the breast
cancer cells (BC) and of 0.034 and 0.15 µM against
nasopharynx carcinoma cells (KB), respectively. Moreover,
(s, 9-C), 113.4 (s, 6-C), 109.9 (d, 8′-C), 102.0 (t, OCH
(s, 1′-C), 61.2 (d, 1-C), 60.4 (q, 17-OCH ), 60.1 (t, 22-C), 59.7
), 54.8 (d, 11-C), 54.7
d, 13-C), 42.3 (t, 12′-C), 41.9 (d, 4-C), 41.6 (q, NCH ), 39.7 (t,
′-C), 28.8 (t, 4′-C), 24.2 (t, 14-C), 20.4 (q, 5-OCOCH ), 15.8
q, 16-CH ), 9.7 (q, 6-CH ); IR (KBr) 3530, 3500, 2940, 2250w,
770, 1740, 1630, 1595, 1520, 1478 cm ; HR-FABMS m/z
2
O), 64.6
3
(
(
3
(
1
7
d, 3-C), 59.6 (d, 21-C), 55.2 (q, 7′-OCH
3
3
3
1
b and 3b showed antitubercular activity against Myco-
3
3
bacterium tuberculosis H37Ra at MIC of 0.13 and 2.0 µM,
respectively. More details of other biological activities of
these compounds, evaluation of the antitumor activity, and
the isolation and structure elucidation of other minor
components are currently in progress.16
-
1
+
71.2693 (calcd for C40
C 62.33%, H 5.49%, N 7.27%, calcd for C40
62.00%, H 5.48%, N 6.90%.
43 4
H N O10S [M + H] 771.2700); anal.
42 4
H N O10S, C
Ectein a scid in 786 (3b): colorless prisms from methanol,
mp 197-199 °C (dec); [R]24
-156.9 (c 0.6, CHCl ); CD ∆ꢀ nm
(c 0.13 mmol/L, methanol, 24 °C) 0 (314), -13.0 (291), -2.3
D
3
Exp er im en ta l Section
1
(
6
(
)
4
247), -60.1 (223), 0 (214), +70.6 (207); H NMR (CDCl
.65 (1H, s, 15-H), 6.49 (1H, s, 5′-H), 6.37 (1H, s, 18-OH), 6.20
1H, s, 8′-H), 6.06 (1H, d, J ) 1.2 Hz, OCHO), 6.02 (1H, d, J
1.2 Hz, OCHO), 5.49 (1H, br s, 6′-OH), 4.67 (1H, dd, J )
.3, 1.2 Hz, 11-H), 4.60 (1H, d, J ) 11.6 Hz, 22-Hâ), 4.31 (1H,
d, J ) 2.1 Hz, 1-H), 4.31 (1H, dd, J ) 11.6, 2.1 Hz, 22-HR),
.18 (1H, br s, 4-H), 4.07 (1H, d, J ) 2.8 Hz, 21-H), 3.85 (3H,
s, 17-OCH ), 3.74 (1H, dd, J ) 4.3, 2.8 Hz, 3-H), 3.66 (1H, d,
J ) 14.3 Hz, 12′-Hâ), 3.63 (3H, s, 7′-OCH ), 3.43 (1H, ddd, J
9.2, 2.8, 1.2 Hz, 13-H), 3.01 (1H, dd, J ) 17.7, 9.2 Hz, 14-
3
) δ
Gen er a l Exp er im en ta l P r oced u r es. CD was obtained on
a J ASCO J -720WI. Optical rotations were measured on a
Horiba-SEPA. IR spectra were obtained on a Hitachi 260-10.
Melting points determined with a Yanagimoto micromelting
1
13
point apparatus are uncorrected. H and C NMR spectra were
recorded at 500 and 125.65 MHz, respectively, on a J EOL
J NM-LA-500 FT-NMR spectrometer and at 300 and 75 MHz,
respectively, on a Bruker Avance DPX-300 FT-NMR spectrom-
eter (ppm, J in Hz with TMS as internal standard). Elemental
analysis: Perkin-Elmer Model 240B. TLC: precoated Kieselgel
4
3
3
)
HR), 2.99 (1H, ddd, J ) 12.2, 8.2, 4.0 Hz, 3′-HR), 2.86 (1H,
ddd, J ) 12.2, 5.2, 4.9 Hz, 3′-Hâ), 2.70 (1H, d, J ) 17.7 Hz,
14-Hâ), 2.62 (1H, ddd, J ) 15.9, 8.2, 4.9 Hz, 4′-Hâ), 2.46 (1H,
3
6
0 F254 plates (Merck, 0.25 mm thick). Column chromatogra-
phy: Kieselgel 60 [Merck, 70-230 (for open chromatography)
and 230-400 mesh (for flash chromatography)]. Sephadex LH-
ddd, J ) 15.9, 5.2, 4.0 Hz, 4′-HR), 2.31 (3H, s, 16-CH ), 2.27
2
0 [Pharmacia Biotech].
(3H, s, 5-OCOCH
Hz, 12′-HR)*, 2.07 (3H, s, 6-CH
the methyl signal); 13C NMR (CDCl
(s, 5-OCOCH ), 148.0 (s, 18-C), 147.0 (s, 17-C), 146.1 (s, 7-C),
3
), 2.24 (3H, s, 12-CH
3
), 2.19 (1H, d, J ) 14.3
) (* the signal overlapped with
) δ 171.8 (s, 11′-C), 168.9
An im a l Ma ter ia l. The tunicate was identified by T. Nish-
3
ikawa of the Nagoya University Museum as Ecteinascidia
3
1
4,15
thurstoni Herdman 1981.
3
Extr a ction a n d Isola tion . The tunicate Ecteinascidia
thurstoni Herdman 1891 was collected by scuba divers on the
145.0 (s, 6′-C), 144.7 (s, 7′-C), 142.2 (s, 5-C), 140.7 (s, 8-C),
130.6 (s, 16-C), 129.5 (s, 10′-C), 129.4 (s, 20-C), 124.5 (s, 9′-C),

Notes
J ournal of Natural Products, 2002, Vol. 65, No. 6 937
1
22.6 (d, 15-C), 120.3 (s, 10-C), 120.2 (s, 19-C), 117.6 (s, 21-
CN), 114.5 (d, 5′-C), 114.1 (s, 6-C), 111.6 (s, 9-C), 109.4 (d, 8′-
C), 102.3 (t, OCH O), 71.0 (d, 4-C), 67.7 (t, 12′-C), 61.8 (t, 22-
C), 61.6 (s, 1′-C), 60.7 (d, 1-C), 60.6 (d, 21-C), 60.4 (q, 17-OCH ),
), 54.9 (d, 11-C), 54.6 (d, 13-C),
), 39.9 (t, 3′-C), 29.1 (t, 4′-C), 24.9 (t, 14-C), 20.8
), 16.0 (q, 16-CH ), 10.1 (q, 6-CH ); IR (KBr)
430, 2930, 2250w, 1760, 1730, 1620, 1590, 1510, 1460 cm
993. (c) Hendriks, H. R.; Fiebig, H. H.; Giavazzi, R.; Langdon, S. P.;
J imeno, J . M.; Faircloth, G. T. Ann. Oncol. 1999, 10, 1233-1240. (d)
J in, S.; Gorfajn, B.; Faircloth, G.; Scotto, K. Proc. Natl. Acad. Sci.
U.S.A. 2000, 97, 6775-6779. (e) Zewail-Foote, M.; Li, V.; Kohn, H.;
Bearss, D.; Guzman, M.; Hurley, L. H. Chem. Biol. 2001, 135, 1-17.
(f) Zewail-Foote, M.; Hurley, L. H. J . Am. Chem. Soc. 2001, 123,
6485-6495. (g) Takebayashi, Y.; Pourquier, P.; Zimonjic, D. B.;
Nakayama, K.; Emmer, S.; Ueda, T.; Urasaki, Y.; Kanzaki, A.;
Akiyama, S.; Popescu, N.; Kraemer, K. H.; Pommier, Y. Nat. Med.
2
3
6
4
0.0 (d, 3-C), 55.2 (q, 7′-OCH
1.8 (q, NCH
3
3
(q, 5-OCOCH
3
3
3
-
1
3
;
2
001, 7, 961-966.
+
HR-FABMS m/z 787.2652 (calcd for C40
87.2649).
Tr a n sfor m a tion of 1b to 1a . Ecteinascidin 770 (1b, 7.7
43 4
H N O11S [M + H]
(
3) (a) Corey, E. J .; Gin, D. Y.; Kania, R. S. J . Am. Chem. Soc. 1996,
118, 9202-9203. (b) Martinez, E. J .; Corey, E. J . Org. Lett. 2000, 2,
993-996.
7
(
4) Cuevas, C.; Perez, M.; Martin, M. J .; Chicharro, J . L.; Fernandez-
Rivas, C.; Flores, M.; Francesch, A.; Gallego, P.; Zarzuelo, M.; Calle,
F. de la; Garcia, J .; Polanco, C.; Rodriguez, I.; Manzanares, I. Org.
Lett. 2000, 2, 2545-2548.
mg, 0.01 mmol) was dissolved in a mixture of acetonitrile and
water [3:2 (v/v), 2.5 mL], and silver nitrate (34 mg, 0.3 mmol,
3
0 equiv) was added to this solution. The suspension was
stirred at room temperature for 11 h. A mixture of saturated
aqueous sodium chloride solution and saturated aqueous
sodium bicarbonate solution [1:1 (v/v), 6.25 mL] was added,
and the mixture was stirred vigorously at room temperature
for 15 min. The reaction mixture was extracted with dichlo-
romethane (3 × 20 mL), and the combined organic layers were
dried with sodium sulfate and filtered through a pad of
cellulose powder. The filtrate was concentrated to give ectein-
ascidin 743 (1a , 7.2 mg, 96.9%) as a colorless solid, which was
identical in all respects with that of the authentic sample.
(5) Martinez, E. J .; Owa, T.; Schreiber, S. L.; Corey, E. J . Proc. Natl.
Acad. Sci., U.S.A. 1999, 96, 3496-3501.
6) For approach to the total synthesis of ecteinascidins, see: (a) Saito,
N.; Tashiro, K.; Maru, Y.; Yamaguchi, K.; Kubo, A. J . Chem. Soc.,
Perkin Trans. 1 1997, 5953-69. (b) Endo, A.; Kann, T.; Fukuyama,
T. Synlett. 1999, 1103-1105.
(
(7) The structure of ecteinascidin 759B was tentatively assigned as the
N-oxide of 1a 1b on the basis of its mass spectral data; however,
analysis of the 1H and C NMR data of this compound suggested
the assignment of structure 3a as the S-oxide of 1a . See: Rinehart,
K.; Sakai, R.; Holt, T. G.; Westfield, N. J . U.S. Patent 5,256,663, 1993.
13
(
8) In our previous research on the extraction and isolation of saframycin
antibiotics, there was an inherent difficulty in the development of
these satellite antibiotics for chemotherapeutic agents because of their
extremely low production in culture. A satisfactory way of circum-
venting the low production level, however, was found quite unexpect-
edly with the observation that cyanide was directly incorporated in
the cyano residue of saframycin A; see: Arai, T.; Takahashi, K.;
Nakahara, S.; Kubo, A. Experientia 1980, 36, 1025-1027; Arai, T.;
Takahashi, K.; Ishiguro, K.; Yazawa, K. J . Antibiot. 1980, 33, 951-
Ack n ow led gm en t. We are grateful to T. Nishikawa of the
Nagoya University Museum for his identification of the Thai
tunicate. We are also grateful to J . Tanaka of the Department
of Chemistry, Biology, and Marine Science, University of the
Ryukyus, for his advice on the collection of the tunicate. We
thank K. Yazawa (Research Center for Pathogenic Fungi and
Microbial Toxicoses, Chiba University) for his kind advice
during extraction, and K. Masuda (Suntory Institute for
Bioorganic Research) for performing the HRFABMS experi-
ments. We are also indebted to Bioassay Research Facility,
National Center for Genetic Engineering and Biotechnology
9
60. And also see quinocarcin: Saito, H.; Hirata, T. Tetrahedron Lett.
987, 35, 4065-4068. Cyanocycline A: Zmijewski, J r. M. J .; Goebel,
1
M. J . Antibiot. 1982, 35, 524-526. Gould, S. J .; He, W.; Cone, M. C.
J . Nat. Prod. 1993, 56, 1239-1245.
(
9) This discrepancy could be explained by assuming that in the IR
spectrum the introduction of the highly oxygenated groups into the
molecule results in quenching the CN absorption intensity, such as
(BIOTEC), Science Technology and Environment Ministry of
in saframycin A:
8
Bellamy, L. J . In The Infra-red Spectra of Complex
Thailand, for testing cytotoxic activity and antitubercular
activity. This research was supported by a Grant (No. BT-38-
Molecules; Methuen: London, 1957.
(
10) These spectral changes are consistent with those reported for
saframycins A and S, and naphthyridinomycin and cyanocycline A.8
11) The CD spectra of 1b (from the Thai tunicate) and 1a (from the
Caribbean tunicate) displayed almost superimposable curves. There-
fore, these compounds have the same absolute confirguration.
0
6-NP1-09-09) from the BIOTEC, Thailand, and a Grant-in-
(
Aid for Scientific Research(B) (No. 14370725) from the Min-
istry of Education, Culture, Sports, Science and Technology,
J apan.
(
12) Rinehart reported the optical rotation of 1b (from the Caribbean
2
5
tunicate), [R]
D
+52° (c 0.1, methanol), in contrast with that of 1b
20
(
synthetic compound), [R]
13) Silver nitrate was particularly effective for this type of transformation.
D 2 2
-35° (c 0.1, CH Cl ).
Su p p or tin g In for m a tion Ava ila ble: Color pictures of Ecteinas-
cidia thurstoni Herdman 1891 are available free of charge via the
Internet at http://pubs.acs.org.
(
See: (a) Fukuyama, T.; Nunes, J . J . Am. Chem. Soc. 1988, 110, 5196-
5
198. (b) Saito, H.; Kobayashi, S.; Uosak, Y.; Sato, A.; Fujimoto, K.;
Miyoshi, K.; Ashizawa, T.; Morimoto, M.; Hirata, T. Chem. Pharm.
Bull. 1990, 38, 1278-1285. (c) Ganner, P.; Ho, W. B.; Shin, H. J .
Am. Chem. Soc. 1993, 115, 10742-10753.
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1) (a) Wright, A. E.; Folreo, D. A.; Gunawardana, G. P.; Gunasechera,
(
14) Herdman W. A On the genus Ecteinascidia and it relations, with
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15) Kott. P. The Australian Ascidiacea Part I, Phlebobrancha and
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16) T. Fukuyama of the University of Tokyo has just finished the total
synthesis of (-)-ecteinascidin 770, and the synthetic sample has been
identified with our natural one in all respects; see: Endo, A.;
Yanagisawa, A.; Abe, M.; Tohma, S.; Kan, T.; Fukuyama, T. J . Am.
Chem. Soc., in press. We thank T. Fukuyama for communicating the
results prior to publication.
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512. (b) Rinehart, K. L.; Holt, T. G.; Fregean, N. L.; Stroh, J . G.;
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9
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