Didemnilactone and neodidemnilactone, two new fatty acid metabolites possessing a 10-membered lactone from the tunicate Didemnum moseleyi (Herdman)

Article abstract of DOI:10.1016/S0040-4039(00)93445-2

Didemnilactone (1) and neodidemnilactone (2), two new fatty acid metabolites possessing a 10-membered lactone were isolated from the colonial tunicate Didemnum moseleyi (Herdman). Their structures including absolute stereochemistry were determined on the

Full text of DOI:10.1016/S0040-4039(00)93445-2

Tetzahedron Letters, Vol.32, No.38, pp 5127-5128, 1991
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Didemnilactone and Neodidemnilactone, Two New Fatty Acid Metabolites
Possessing a 10-Membered Lactone from the Tunicate Didemnum moseleyi (Herdman)
Haruki Niwa,* Hideaki Inagaki, and Kiyoyuld Yamada
Department ofChemistry, Faculty ofScience, Nagoya University, Chikusa, Nagoya 464, Japan
Abstract: Didemnilactone (I) and neodidemnilactone (2), two new fatty acid metabolites possessing a 10-
membered lactone were isolated from the colonial tunicate Didemnum rnoseleyi (Herdman). Their structures
including absolute stereochemistry were determined on the basis of spectral studies and the enantioselective
synthesis of the antipode of 2.
We have examined the constituents of the colonial tunicate Didemnum moseleyi (Herdman) collected at Hinata
Island of Toba City, Japan and isolated two new fatty acid metabolites, designated as didemnilactone (1) and
neodidemnilactone (2). We wish to report herein the structural elucidation of these metabolites on the basis of
spectral data and chemical synthesis.
OH
"
l
o
.OH
0
0
1
didemnilactone
2 neodidemnilactone
The EK)Ac-soluble material obtained from the MeOH extract of the tunicate was partitioned between hexane
and MeOH-H20 (9:1 v/v). The MeOH-H20-soluble material was further partitioned between CH2C12 and
MeOH-H20 (3:1). The hexane- and CH2C12-soluble materials were subjected to repeated column
chromatography on silica gel and alumina followed by reversed-phase HPLC [ODS, CH3CN-H20 (70:30)] to
give didemnilactone (1)1 (colorless oil; 5.7 x 10--5% wet weight) and neodidemnilactone (2)2 (colorless oil; 2.5 x
10-5% wet weight). The extensive studies of their IH and 13C NMR, mass, IR, and UV spectra revealed the
structures of didemnilactone and neodidemnilactone to be as depicted in formula 1 and 2 (or the antipode),
respectively.
In order to establish the absolute stereostructure of didemnilactone (1) and neodidemnilactone (2)
unambiguously, the synthesis of (8S,9R)-neodidemnilactone (11) was performed. Wittig reaction of 3,4-0-
isopropylidene-2-deoxy-D-ribose (3)3 with ylide 4 prepared by reaction of (4-carboxybutyl)triphenyl-
phosphonium bromide with NaN(SiMe3)2, in toluene at -78 °C ---) -20 °C afforded selectively (Z)-olefinic acid
5,4 which was converted into methyl ester 6 with CH2N2 (58% overall). Swern oxidation of 6 gave aldehyde 7
(95%). Wittig reaction of 7 with ylide 8 prepared by reaction of (E,E)-(2,4-decadienyl)triphenylphosphonium
chloride5 with NaN(SiMe3)2, in toluene at -78 °C provided selectively (5Z,lOZ,12E,14E)-tetraene 9 (62%).
Acidic hydrolysis (AcOH-H20) of the acetonide group in 9 and subsequent basic hydrolysis (LiOH, MeOH-
H20) of the ester group yielded diol acid 10 (34% overall). Lactonization of 10 by means of the Yamaguchi's
method6 furnished dextrorotatory (8S,9R)-neodidemnilactone (U) [[tt]D18 +218° (c 0.054, MeOH), 28%],
whose spectral properties except for the sign of the specific rotation were identical with those of natural,
5127

5128
R1
C
0
2
R2
~
pph3
~6/ o
8
O,.~k_.~OH
Ph3 P4X,/'VCO~
5
6
R1 = CH2E~-I,
R~ = C H ~ H ,
R1 =CLIO,
R2 = H
~ = CH3
R2=CH3
3
4
7
OH
OH
0
11
levorotatory (8R,9S)-neodidemnilactone (2) [[~]D22-200° (c 0.17, MeOH)]. Thus, the absolute
stereochemistry of neodidemnilactone (2) is established to be 8R,9S. Further, the absolute stereochemistry of
didemnilactone (I) may be concluded to be 8R,9S from the similarity of the chiroptical properties of 1 and 2.7
Didemnilactone (1), neodidemnilactone (2), and the corresponding diol acids obtained by hydrolysis of I and
2 exhibit week binding activity (IC50 50 ~ 100 ~¢1) to leukotriene B4 receptors of human polymorphonuclear
leukocyte membrane fractions.
Acknowledgment: We are grateful to Dr, Masaaki Toda, Ono Pharmaceutical Co., Ltd. for biological tests.
Notes and References
1. 1:C20H2803 [m/z 316.2048 (M+), A +0.9 mmu]; [IX]D22-190° (c 0.18, MeOH); IR (CHC13) 3590, 3450,
1730 cm-1; UV (MeOH) ~.max 261 (e 24,600), 271 (30,500), 279 nm (25,400); EIMS m/z (relative intensity)
316 (M+, 42), 298 (14), 177 (12), 160 (100), 139 (42); ]H NMR (C6D6, 270 MHz) 8 0.88 (3 H, t, J = 7.6
Hz), 1.32 (1 H, m), 1.63 (1 H, m), 1.95 (2 H, m), 1.85-2.10 (4 H, m), 2.19 (1 H, m), 2.62 (1 H, m), 2.69
(2 H, dt, J = 1.0, 6.6 Hz), 3.65 (1 H, ddd, J -- 9.1, 3.9, 3.9 Hz), 5.22 (1 H, dd, J -- 11.5, 9.1 Hz), 5.36 (1
H, m), 5.35-5.40 (1 H, m), 5.41 (1 H, m), 5.57 (1 H, dt, J = 14.7, 6.6 Hz), 5.75 (1 H, m), 5.75 (1 H, dd,
J = 9.1, 9.1 Hz), 6.02 (1 H, ddt, J = 14.7, 11.2, 1.0 Hz), 6.17 (1 H, dd, J = 11.5, 11.5 Hz), 6.18 (1 H, dd,
J = 14.7, 11.2 Hz), 7.03 (1 H, dd, J = 14.7, 11.5 I-Iz); 13C NMR (C6D6, 67.8 MHz) 8 14.3 (q), 20.8 (t),
25.4 (t), 26.3 (t), 30.8 (t), 32.6 (t), 34.7 (t), 72.4 (d), 72.6 (d), 125.4 (d), 126.3 (d), 126.7 (d), 127.0 (d)
131.2 (d), 131.7 (d), 132.9 (d), 134.6 (d), 134.9 (d), 136.5 (d), 172.5 (s).
2. 2:C20H3003 [m/z 318.2191 (M+), A --0.3 mmu]; [CC]D22 -200° (c 0.17, MeOH); IR (CHC13) 3570, 3450,
1730 cm-1; UV (MeOH) ~,max 261 (e 22,900), 271 (29,100), 279 nm (24,000); EIMS m/z (relative intensity)
318 (M+, 49), 300 (12), 179 (33), 162 (100), 139 (67); tH NMR (C6D6, 270 MHz) 8 0.86 (3 H, t, J = 7.6
Hz), 1.10-1.40 (7 H, m), 1.63 (1 H, m), 1.85-2.10 (6 H, m), 2.20 (1 H, m), 2.62 (1 H, m), 3.65 (1 H,
ddd, J = 9.1, 3.9, 3.9 Hz), 5.22 (1 H, dd, J = 11.5, 9.1 Hz), 5.37 (1 H, m), 5.62 (1 H, dt, J = 14.7, 6.6
Hz), 5.74 (1 H, dd, J = 9.1, 9.1 Hz), 5.77 (1 H, m), 5.99 (1 H, ddt, J = 14.7, 11.2, 1.0 Hz), 6.19 (1 H,
dd, J = 11.5, 11.5 Hz), 6.20 (1 H, dd, J --- 14.7, 11.2 Hz), 7.03 (1 H, dd, J = 14.7, 11.5 Hz); 13C NMR
(C6D6, 67.8 MHz) ~ 14.2 (q), 22.8 (t), 25.4 (t), 26.3 (t), 29.2 (t), 31.7 (t), 32.7 (t), 33.0 (t), 34.7 (t), 72.4
(d), 72.6 (d), 125.5 (d), 126.3 (d), 126.8 (d), 131.1 (d), 131.7 (d), 135.0 (d), 136.7 (d), 136.8 (d), 172.4
(s).
3. Corey, E. J.; Marfat, A.; Goto, G.; Brion, F. J. Am. Chem. Soc. 1980, 102, 7984.
4. Satisfactory spectral and analytical data were obtained for all new compounds. All yields refer to materials
purified by column chromatography on silica gel.
5. This phosphonium salt was prepared from (g,g)-2,4-decadien-l-ol by reaction with Ph3P (1 equiv) and HC1
(1 equiv) in MeOH at room temperature (65%); cf. Riiegg, R; Schwieter, U; Ryser, G; Schudel, P.; Isler, O.
Helv. Chim. Acta 1961, 44, 985.
6. Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M. Bull. Chem. Soc. Jpn. 1979, 52, 1989.
The isomeric 9-membered lactone was not detected.
7. A recent paper reports the occurrence of the related compounds having a 9-membered lactone and a triene;
Lindquist, N.; Fenical, W. Tetrahedron Lett. 1989, 30, 2735.
(Received in Japan 18 June 1991)