Synthesis of (-)-idiadione, a furanosesterterpene isolated from a marine sponge Spongia idia

Article abstract of DOI:10.3987/COM-01-9311

(-)-Idiadione (1) , a furanosesterterpene isolated from a marine sponge Spongia idia, was synthesized, starting from (S)-(-)-citronellal (2). The absolute configuration of naturally occurring 1 is established as (S).

Full text of DOI:10.3987/COM-01-9311

HETEROCYCLES, Vol. 55, No. 10, 2001, pp. 1839 - 1842, Received, 31st July, 2001
SYNTHESIS OF (-)-IDIADIONE, A FURANOSESTERTERPENE
ISOLATED FROM A MARINE SPONGE SPONGIA IDIA
Yoshihiro Noda* Hiroyuki Hashimoto and Toshie Norizuki
Department of Materials Chemistry and Engineering, College of Engineering,
Nihon University, Tamura-machi, Koriyama, Fukushima, 963-8642 Japan
Abstract-(-)-Idiadione (1) , a furanosesterterpene isolated from a marine sponge
Spongia idia, was synthesized, starting from (S)-(-)-citronellal (2) . The absolute
configuration of naturally occurring 1 is established as (S) .
The linear furanosesterterpene idiadione (1) was first isolated in 1980 by Faulkner et al.1 from a marine
sponge Spongia idia (Leiosella idia). Faulkner reported that idiadione (1) is toxic to the sea star, brine
shrimp and ectoproct. 1 has also antifeedant activity2 against fish.
The structure of 1 has been elucidated by spectroscopic method and chemical degradation . Faulkner has
also reported the isolation of a structure-related marine natural product, furospinulosin-11
(furospinosuline 13) (3), which was also isolated from the marine sponge Spongia idia. Idiadione (1)
possesses one stereogenic carbon in a highly oxygenated furospinulosin-1(3) skeleton. No indication of the
absolute configuration at the chiral center in 1 was mentioned by Faulkner .
22
24
O
O
O
11
idiadione (1)
14
6
2
20
O
furospinulosin-1 (3)
(furospinosuline-1)
Scheme 1.
We here describe the first enantioselective total synthesis of (S)-(-)-idiadione (1) using (S)-(-)-citronellal
(2) as the starting material .
Scheme 2 shows retrosynthetic analysis for 1. The target compound (1) is divided into left-hand part A
and right-hand part (perillene part) B.
To produce the left-hand part A of the target molecule, we protected (S)-(-)-citronellal by ethylene glycol

idiadione (1)
O
S
S
S
S
Br
+
A
B
bromoperillene (10)
S
S
+
CHO
(7)
(S)-(-)-citronellal (2)
Scheme 2. Retrosynthetic analysis of idiadione (1)
in the presence of a catalytic amount of p-toluenesulfonic acid in refluxing benzene and obtained the
4
acetal (4) . Oxidation of 4 with 70% t-BuOOH in the presence of SeO2 in CH2Cl2 at room temperature,
afforded a mixture of aldehyde and alcohol. Without purification, the mixture was reduced by NaBH4 to
the corresponding alcohol (5) (50%, three steps). Bromination of the alcohol (5) under the well-described
conditions (tetrabromomethane / triphenylphosphine) afforded the bromide (6) in 82% yield.
2-Isobutyl-1,3-dithiane (7) was prepared from isovaleraldehyde and 1,3-propanedithiol in 70% yield. The
bromide (6) was employed for the alkylation of 7 (n-BuLi / THF) to give 1,3-dioxolane (8) (75% yield),
5
which was readily converted to 1,3-dithiane (9) by 1,3-propanedithiol and Zn(OTf)2 in 77% yield.
O
O
a, b, c, d
X
CHO
(S)-(-)-citronellal (2)
X=H (4)
X=OH (5)
X=Br (6)
e
f
O
O
S
S
S
S
S
S
(8)
(9)
O
Ph3P
g, h
i
(13)
S
S
S
S
X
X=OH (11)
X=O (12)
O
j
S
S
S
S
(S)-(1)
(14)
Scheme 3. Reagents and conditions: (a) ethylene glycol, benzene, p-TsOH, reflux ; (b) SeO2, 70%t-BuOOH,
CH2Cl2, rt ; (c) NaBH4, MeOH, rt, 50% for three steps; (d) CBr4, Ph3P, THF, rt, 82%; (e) 2-isobutyl-1,3-dithiane
(7),n-BuLi, (6), THF, -20oC, 75%; (f) 1,3-propanedithiol, Zn(OTf)2, CH2Cl2 , rt, 77%; (g) n-BuLi, propylene
oxide, THF, -20oC, 58%; (h) TFAA, DMSO, Et3N, CH2Cl2, -78oC, 82%; (i) Wittig reagent (13),THF, -30oC, 40% ;
(j) HgCl2, CaCO3, MeCN-H2O, rt, 46%.

In the first attempt, alkylation of 9 with bromoperillene (1 0)6 (the right-hand part B) (n-BuLi / THF,
-20oC) ( LDA / THF, -78 to -30oC) was unsuccessful under these conditions.
We then turned our attention to another approach for the synthesis of idiadione (1). 1,3-Dithiane (9) was
treated with n-BuLi and propylene oxide to give alcohol (1 1) (58% yield). The alcohol (1 1) was converted
to the methyl ketone (1 2) by Swern oxidation7(TFAA, DMSO, Et3N in CH2Cl2 , 82% yield). We
undertook coupling with the appropriate Wittig reagent (1 3).8 Treatment of the phosphonium salt with
n-BuLi in THF led to the formation of a yellow solution of 1 3, which , upon addition of methyl ketone
(1 2) at room temperature, furnished 40% yield of an inseparable mixture of the 6E and 6Z isomers of 1 4,
15 (ratio 6:1).9 Without purification, the mixture was hydrolyzed with HgCl2 in the presence of CaCO3 in
aqueous MeCN.10 The hydrolyzed products can be separated by preparative TLC. The structural data of
the major product (1) (46% yield) are in agreement with that of natural idiadione. Synthetic optically
21
active 1 had identical specific rotation with that of natural 1 { [a]D -6.6o (c 0.26 , CHCl3) for
synthetic , lit.,1 [a]D-6.6o (c 2.6 , CHCl3) for natural } and from its relation to (S)-(-)-citronellal, the
(S)-configuration for the natural product can be established.
In summary, we have accomplished the total synthesis of idiadione (1) in an optically active form from
(S)-(-)-citronellal, and the absolute configuration of the natural product was determined to be 11S.
REFERENCES
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Kreiser, and V. Ruschenbaum, Helv. Chim. Acta, 1987, 7 0, 445.
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the 22 (14E) and 24 methyl signals in the 13C-NMR spectrum of the major product (1 4) {d 18.4,18.5}.
10. D. Seebach, Synthesis, 1969, 17.