Carotenoids and related polyenes. Part 8. Total synthesis of optically active mytiloxanthin applying the stereoselective rearrangement of tetrasubstituted epoxide

Article abstract of DOI:10.1039/b201228f

Biomimetic synthesis of mytiloxanthin 1 was accomplished with stereoselective rearrangement of the tetrasubstituted epoxide 5 as a key reaction. This is the first total synthesis of optically active all-E mytiloxanthin 1.

Full text of DOI:10.1039/b201228f

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Carotenoids and related polyenes. Part 8.1 Total synthesis of
optically active mytiloxanthin applying the stereoselective
rearrangement of tetrasubstituted epoxide†
1
Chisato Tode, Yumiko Yamano and Masayoshi Ito*
Kobe Pharmaceutical University, Motoyamakita-machi, Higashinada-ku, Kobe, 658-8558,
Japan
Received (in Cambridge, UK) 1st February 2002, Accepted 14th May 2002
First published as an Advance Article on the web 7th June 2002
Biomimetic synthesis of mytiloxanthin 1 was accomplished with stereoselective rearrangement of the tetrasubstituted
epoxide 5 as a key reaction. This is the first total synthesis of optically active all-E mytiloxanthin 1.
In a previous communication,7 we reported the first total syn-
Introduction
thesis of mytiloxanthin 1 which includes the new construction
Mytiloxanthin 1, with a unique cyclopentyl enolic β-diketone
of conjugated β-diketones 10a,b through the cyclopentyl com-
group conjugated to a polyene chain, was first isolated from
pound 8 (Scheme 2), prepared by application of the stereo-
Mytilus californianus by Scheer in 1940.2 Its structure and syn-
selective rearrangement of epoxide 5. The present paper is
thesis of the 9Z-isomer were reported by Weedon’s group,3 they
developed the new synthetic route to polyene β-diketones using
concerned with a full account of the experiments.
Claisen type condensation between polyene esters and methyl
ketones. The absolute configuration was determined by Maoka
and Fujiwara in 1996.4 The cyclopentyl end group of myti-
loxanthin 1 is believed3 to be formed in Nature from the
epoxide end group of 5,6-epoxy carotenoids such as halocyn-
thiaxanthin 2 by cleavage of the oxirane ring at the C-5 position
and successive ring contraction (a pinacolic rearrangement)
(Scheme 1, route a).
Results and discussion
It has been previously reported5b that BF3ؒOEt2-treatment of
the epoxide 4 (Scheme 2) with the acetoxy ethyl group at the C-6
position resulted in a very slow reaction and in a low-yield
formation of the C-5 diastereomer 6 instead of the desired
compound 7. Efficient preparation of 7 was obtained from the
investigation of other Lewis acids with an aminium salt. Thus,
treatment of the epoxide 4 with tris(4-bromophenyl)aminium
hexachloroantimonate 98 in CH2Cl2 was found to afford 7 in
reasonable yield (69%) (Scheme 2). In order to accomplish the
biomimetic synthesis of 1 in an analogous manner to the suc-
cessful synthesis of 3, the acetoxy group at the C-3 position in 4
was replaced by the tert-butyldimethylsilyl (TBS) ether leading
to epoxide 5. The synthetic route of mytiloxanthin 1 was there-
fore planned through conversion of 5 to the cyclopentyl ketone
We found5 that the acyclic-tetrasubstituted olefinic com-
pounds and the cyclopentyl ketone were derived by Lewis acid-
promoted stereoselective rearrangement of epoxy compounds.
Then, the biomimetic total synthesis1,6 of crassostreaxanthin B
3 possessing the acyclic-tetrasubstituted olefinic end group was
achieved using this rearrangement reaction.
† We have employed the numbering system used in carotenoids.
Scheme 1
DOI: 10.1039/b201228f
J. Chem. Soc., Perkin Trans. 1, 2002, 1581–1587
This journal is © The Royal Society of Chemistry 2002
1581

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Reduction of 8 with NaBH4 followed by protection of
the resulting hydroxy group with p-methoxybenzyloxymethyl
(PMBM) chloride11 gave compound 14 (62% from 8), which
was reduced with LAH to provide the alcohol 15 (99%). This
was subjected to oxidation with o-iodoxybenzoic acid12 (IBX)
to yield the aldehyde 16 (93%), which was reacted with vinyl-
lithium prepared from the vinyl bromide 1713 and ButLi fol-
lowed by oxidation with IBX to provide the ketone 18 (60%
from 16). Its structure was confirmed by IR (ν 1669 cmϪ1) and
1H NMR data [δ 6.53 (1H, tq-like, J 5, 1, 10-H), 4.26 (2H, m,
11-H2)]. Deprotection of the PMBM group in 18 with DDQ11b
gave the alcohol 19 (88%), which was treated with DMSO and
Ac2O to afford the enolic β-diketone 20 (36%) and the acetate
21 (33%). Attempts to prepare 20 from 19 under other oxid-
ation conditions (e.g., DMSO–oxalyl chloride, DMSO–TFAA,
DMSO–SO3ؒPy, NMO–TPAP and IBX) were unsuccessful.
The 1H NMR spectrum of 20 had a broad one-proton signal at
δ 16.15 and a sharp one-proton resonance at δ 5.81. In addition,
its IR spectrum showed an absorption at 1583 cmϪ1 exhibiting
the presence of a strongly hydrogen-bonded carbonyl group.
These spectral data confirmed the presence of a completely
enolic β-diketone structure. The structure of 21 was revealed by
the following 1H NMR data [an acetoxy methyl signal appeared
at δ 2.14 (3H, s) and a proton signal (δ 4.23) due to C-6 shifted
downfield compared to the corresponding signal (δ 4.04) of 19].
Unfortunately, direct conversion of 20 into the C15-β-
diketone aldehyde 10a (Scheme 2) by deprotection of the allylic
TBS group and subsequent oxidation of the resulting alcohol
using several reagents (IBX, MnO2, etc.) was unsuccessful,
probably due to the instability of the β-diketone part. Thus,
after protection of the β-diketone moiety in 20 by acetylation,
the resulting acetate 22 was partly deprotected with TBAF to
give the allylic alcohol 23 (92%) which was oxidized with IBX
followed by removal of another TBS group with HF to afford
the C15-aldehyde 10b (55% from 23) as shown in Scheme 4. Its
1H NMR spectrum showed no signal from the TBS group but it
did display a pair of doublets attributable to the 11-H (δ 10.17,
d, J 7.5) and 10-H (δ 6.37, d, J 7.5).
Scheme 2
8 and subsequent construction of enolic β-diketone as shown in
Scheme 2.
Starting from the previously prepared optically active
alcohol1 11 (Scheme 3), acetylation followed by epoxidation
with MCPBA gave epoxides 5a,b (5a: 26% from 11; 5b: 48%
from 11), in which the relative configurations between the
silyloxy and epoxy groups were confirmed by H NMR.9 The
1
undesired isomer 5b was returned to the tetrasubstituted olefin
12 by the following deepoxidation procedure. Treatment of 5b
with TMSCl and NaI in dry acetonitrile10 followed by silylation
gave 12 in 60% yield. Reaction of anti-epoxide 5a with aminium
salt 9 provided the desired cyclopentyl compound 8 (63%)
and its deprotected alcohol 13 (30%) which was easily resi-
lylated to give 8 (89%). Consequently, the cyclopentyl ketone
8 was synthesized by the stereoselective rearrangement of
5a in high yield. The structure of 8 was determined from the
following spectral data. Its IR absorption showed a new
carbonyl frequency at 1699 cmϪ1. In its 1H NMR spectrum, the
methylene signal of the C-7 position appeared at δ 2.75 (t),
further downfield than the corresponding signal [δ 2.01
(2H, m)] of 5a, in addition, proton signals on the cyclo-
pentane ring were observed analogous to results reported
previously.5b
The Wittig reaction of 10b with the C10-phosphonium salt
2514 in the presence of KOH as a base in a mixture of water and
propan-2-ol gave condensed products which, after acid
hydrolysis, provided an isomeric mixture of C25-apocarotenals
26 (92% from 10b). Investigations of alternative conditions
(e.g., NaOMe–MeOH, BunLi–CH2Cl2–THF) for optimization
Scheme 3 Reagents and conditions: a, Ac2O, Py; b, MCPBA; c, TMSCl, NaI; d, TBSCl, Et3N, DMAP; e, 9; f, NaBH4; g, PMBMCl, Pri2NEt; h,
LAH; i, IBX; j; 17, ButLi; k, DDQ; l, DMSO, Ac2O.
1582
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Scheme 4 Reagents and conditions: a, Ac2O, Et3N, DMAP; b, TBAF; c, IBX; d, HF; e; HC(OMe)3, cat. Hϩ then 1 M NaOMe; f, KOH then Hϩ; g,
27, KOH.
of this condition resulted in the formation of an unexpected
complex mixture. This is presumably owing to the presence of
the conjugated β-diketone moiety in the molecule. It was not-
able that KOH was the best base in the condensation of the
conjugated polyenes including the β-diketone part. Finally, the
isomeric mixture 26 was condensed with the acetylenic C15-
Wittig salt 2715 in the presence of KOH in propan-2-ol at 0 ЊC
to yield the products (30%), a part of which was separated by
repeated preparative HPLC (PHPLC) in the dark to afford all-
E mytiloxanthin 1, 9Z-isomer 28, 9Z,11Z-one 29 and unidenti-
fied isomers. Three isomers (1, 28 and 29) were respectively
obtained in pure form (all-E 1–9Z 28–9Z,11Z 29 = ca. 1 : 1 : 1).
Spectral data (UV–VIS, 1H NMR and CD) of synthetic
mytiloxanthins (all-E and 9Z-isomers) were in good agreement
with those of natural specimens, respectively.4 Their configur-
ations were confirmed from 2D-nuclear Overhauser enhance-
Column chromatography (CC) was performed on silica gel
(Merck Art. 7734). Short-column chromatography (SCC) was
carried out on silica gel (Merck Art. 7739) under reduced
pressure. Preparative TLC (PTLC) was conducted on silica
gel plates (Merck silica gel 60F254 precoated plates, 0.5 mm
thickness). Low-pressure CC was performed on a Yamazen
Low Pressure Liquid Chromatography System using a Lobar
column (Merck LiChroprep Si 60). Analytical and PHPLC
were carried out on Shimadzu LC-6A, or Waters 510 instru-
ments with UV–VIS detectors.
Standard work-up means that the organic layers or extracts
were finally washed with brine, dried over anhydrous sodium
sulfate (Na2SO4), filtered and concentrated in vacuo below 30 ЊC
using a rotary evaporator. All operations were carried out
under nitrogen or argon. Hexane refers to n-hexane.
1
ment spectroscopy (NOESY) experiments in H NMR spectra
Rearrangement of the epoxide 4 with aminium salt 9
(see Experimental section). 9Z,11Z-Stereochemistry in 29 was
To a solution of 4 (142 mg, 0.5 mmol) in CH2Cl2 (1.5 ml) was
added aminium salt 98 (8.17 mg, 0.01 mmol) at rt and the mix-
ture was stirred at rt for 2 h. Evaporation of the reaction mix-
ture gave a residue, which was purified by SCC (Et2O–hexane,
2 : 3) to afford the cyclopentyl compound 7 (98 mg, 69%) as a
1
determined by H NMR data in comparison with those16 of
9ЈZ,11ЈZ-isomer of halocynthiaxanthin 2 skeletal compound.
This is the first biomimetic total synthesis of optically active
all-E mytiloxanthin 1 by application of the stereoselective
rearrangement of the epoxide 5a with aminium salt 9.
1
colorless oil. Spectral data (IR and H NMR) of this com-
pound were in agreement with those of our previous report.5b
Experimental
UV–VIS spectra were recorded on a JASCO Ubest-55 instru-
ment for ethanol solutions unless otherwise stated. IR spectra
were measured on a Perkin Elmer FT-IR spectrometer, model
2-[(4R)-4-tert-Butyldimethylsilyloxy-2,6,6-trimethylcyclohex-1-
enyl]ethyl acetate 12
To a solution of the alcohol 111 (11.9 g, 0.04 mol) in dry Py
(20 ml) was added Ac2O (15 ml) at rt and the mixture was
stirred at rt for 16 h. The mixture was poured into ice–water and
extracted with Et2O. The extracts were washed successively with
aq. 5% HCl, saturated aq. NaHCO3 and brine. Evaporation of
the dried extracts gave a residue, which was purified by SCC
(Et2O–hexane, 1 : 9) to afford the acetate 12 (12.6 g, 93%) as a
colorless oil; [α]2D6 Ϫ42.6 (c 1.22, MeOH); νmax/cmϪ1 1732 (OAc);
δH (300 MHz) 0.06 (6H, s, SiMe2), 0.89 (9H, s, SiBut), 1.02 and
1.04 (each 3H, s, gem-Me), 1.44 (1H, t, J 12, 2-Hax), 1.61 (1H,
m, 2-Heq), 1.65 (3H, s, 5-Me), 1.99 (1H, dd, J 17 and 9, 4-Hax),
2.05 (3H, s, OAc), 2.11 (1H, dd, J 17 and 7, 4-Heq), 2.34 (2H, dt,
1
Paragon 1000, for chloroform solutions. H NMR spectra at
300 or 500 MHz were determined on a Varian Gemini-300 or a
Varian VXR-500 superconducting FT-NMR spectrometer,
respectively, for deuteriochloroform solutions (tetramethylsi-
lane as internal reference). J-Values are given in Hz. NMR
assignments are given using the carotenoid numbering system.
Mass spectra were taken on a Hitachi M-4100 spectrometer.
Optical rotations were measured on a JASCO DIP-181 polar-
imeter ([α]D-values are in units of 10Ϫ1 deg cm2 gϪ1). CD spectra
were measured on a Shimadzu-AVIV 62A DS circular dichro-
ism spectrometer.
J. Chem. Soc., Perkin Trans. 1, 2002, 1581–1587
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J 13 and 8.5, 7-H2), 3.88 (1H, m, 3-H), 3.99 (2H, t, J 8.5, 8-H2)
(Found: Mϩ, 340.2416. C19H36O3Si requires M, 340.2435).
1-Meβ), 1.29 (3H, s, 5-Me), 1.44 (1H, dd, J 14 and 3, 4-Hβ), 1.66
(1H, dd, J 13.5 and 4.5, 2-Hβ), 1.90 (1H, dd, J 13.5 and 7.5,
2-Hα), 2.01 (3H, s, OAc), 2.71 (1H, dd, J 14 and 8, 4-Hα), 2.75
(2H, t, J 6.5, 7-H2), 4.32 (2H, td, J 6.5 and 2, 8-H2), 4.35 (1H, m,
3-H) (Found: Mϩ, 356.2356. C19H36O4Si requires M, 356.2380).
2-[(1S,4S,6R)- and (1R,4S,6S)-4-tert-Butyldimethylsilyloxy-
2,2,6-trimethyl-7-oxabicyclo[4.1.0]heptan-1-yl]ethyl acetate 5a
and 5b
Deprotected compound 13. [α]2D3 ϩ5.00 (c 1.00, MeOH); νmax
/
A solution of MCPBA (72%, 552 mg, 2.29 mmol) in dry
CH2Cl2 (5 ml) was added to an ice-cooled solution of the
acetate 12 (600 mg, 1.76 mmol) in dry CH2Cl2 (5 ml). After
being stirred at 0 ЊC for 1 h, the reaction mixture was diluted
with Et2O and washed successively with aq. 1% Na2S2O3, satur-
ated aq. NaHCO3 and brine. Evaporation of the dried solvent
gave a residue, which was purified by SCC (Et2O–hexane, 1 : 5)
followed by low-pressure CC (Et2O–benzene, 1 : 19) to afford
the anti-epoxide 5a (174 mg, 28%) and the syn- epoxide 5b (328
mg, 52%) as colorless oils, respectively.
cmϪ1 3612 and 3468 (OH), 1736 (OAc), 1701 (C᎐O); δ (300
᎐
H
MHz) 0.81 (3H, s, 1-Meα), 1.14 (3H, s, 1-Meβ), 1.28 (3H, s,
5-Me), 1.43 (1H, dd, J 14.5 and 3.5, 4-Hβ), 1.66 (1H, dd, J 13.5
and 4.5, 2-Hβ), 1.95 (1H, dd, J 13.5 and 8, 2-Hα), 1.98 (3H, s,
OAc), 2.74 (2H, t, J 6, 7-H2), 2.78 (1H, dd, J 14.5 and 8.5,
4-Hα), 4.27 and 4.31 (each 1H, dt, J 11 and 6.5, 8-H2), 4.44
(1H, m, 3-H) (Found: Mϩ, 242.1535. C13H22O4 requires M,
242.1519).
Reprotection of the alcohol 13
anti-Epoxide 5a. [α]2D2 Ϫ10.0 (c 1.00, MeOH); νmax/cmϪ1 1733
(OAc); δH (300 MHz) 0.03 (6H, s, SiMe2), 0.86 (9H, s, SiBut),
1.03 and 1.15 (each 3H, s, gem-Me), 1.18 (1H, dd, J 13 and 9.5,
2-Hax), 1.33 (3H, s, 5-Me), 1.44 (1H, ddd, J 13, 3.5 and 1.5,
2-Heq), 1.64 (1H, dd, J 14.5 and 7.5, 4-Hax), 2.01 (2H, m, 7-H2),
2.04 (3H, s, OAc), 2.19 (1H, ddd, J 14.5, 5 and 1.5, 4-Heq), 3.77
(1H, m, 3-H), 4.15 (2H, m, 8-H2) (Found: Mϩ, 356.2352.
C19H38O4Si requires M, 356.2380).
To a solution of the alcohol 13 (145 mg, 0.60 mmol) in dry
CH2Cl2 (3 ml) was added Et3N (0.5 ml, 3.6 mmol), DMAP
(110 mg, 0.90 mmol) and a solution of TBSCl (106 mg, 0.70
mmol) in dry CH2Cl2 (3 ml) at rt and the mixture was stirred at
rt for 15 h. The reaction mixture was poured into ice–water, and
extracted with Et2O. The extracts were washed successively with
aq. 5% HCl, saturated aq. NaHCO3 and brine. Evaporation of
the dried extracts gave a residue, which was purified by SCC
(Et2O–hexane, 1 : 4) to afford 8 (191 mg, 89%) as a colorless
oil. Spectral properties of this compound were in agreement
with those of the cyclopentyl compound 8 in the above
rearrangement.
syn-Epoxide 5b. [α]2D2 Ϫ30.0 (c 1.00, MeOH); νmax/cmϪ1 1733
(OAc); δH (300 MHz) 0.03 (6H, s, SiMe2), 0.86 (9H, s, SiBut),
1.06 (6H, s, gem-Me), 1.12 (1H, ddd, J 13, 4 and 2, 2-Heq), 1.28
(3H, s, 5-Me), 1.51 (1H, t, J 12.5, 2-Hax), 1.81 (1H, dd, J 15 and
9.5, 4-Hax), 1.96 (2H, m, 7-H2), 2.00 (1H, ddd, J 14.5, 7 and 1.5,
4-Heq), 2.03 (3H, s, OAc), 3.75 (1H, m, 3-H), 4.07 (2H, m, 8-H2)
(Found: Mϩ, 356.2360. C19H36O4Si requires M, 356.2380).
3-[(1R,4S)-4-tert-Butyldimethylsilyloxy-1,2,2-trimethylcyclo-
pentyl]-3-{[(4-methoxyphenyl)methoxy]methoxy}propyl acetate
14
To a solution of the cyclopentyl compound 8 (255 mg, 0.72
mmol) in MeOH (5 ml) was added NaBH4 (27.2 mg, 0.72
mmol) at 0 ЊC and the mixture was stirred at 0 ЊC for 30 min.
The reaction mixture was poured into ice–water, and extracted
with Et2O. Standard work-up afforded a residue, which was
purified by SCC (Et2O–hexane, 1 : 5) to yield the alcohol (200
mg, 78%) as a colorless oil. Pri2NEt (0.98 ml, 5.60 mmol) and
PMBMCl11 (626 mg, 3.36 mmol) were added to a solution of
the above alcohol (200 mg, 0.56 mmol) in dry CH2Cl2 (2 ml) at
rt. After being stirred at rt for 16 h, the reaction mixture was
diluted with Et2O and the organic layer was washed successively
with aq. 5% HCl, saturated aq. NaHCO3 and brine. Evapor-
ation of the dried solution gave a residue, which was purified by
SCC (acetone–hexane, 1 : 19) to afford the PMBM ether 14 (229
mg, 80%; 62% from 8) as a colorless oil; νmax/cmϪ1 1732 (OAc),
1612 and 1514 (Ph); δH (300 MHz) 0.00 (6H, s, SiMe2), 0.86
(9H, s, SiBut), 0.90, 1.06 and 1.12 (each 3H, s, gem-Me and
5-Me), 1.30 (1H, dd, J 14 and 2, 2-Hβ), 1.80 (4H, m, 4-H2
and 7-H2), 1.94 (1H, dd, J 14 and 9, 2-Hα), 2.03 (3H, s, OAc),
3.50 (1H, t-like, J 4, 6-H), 3.80 (3H, s, OMe), 4.22 (1H, m, 3-H),
4.24 (2H, m, 8-H2), 4.52 and 4.60 (each 1H, d, J 11.5, CH2Ph),
4.71 and 4.82 (each 1H, d, J 7, –OCH2O–), 6.87 and 7.25 (each
2H, d, J 8.5, Ar-H4) (Found: Mϩ, 508.3236. C28H48O6Si requires
M, 508.3232).
Conversion of epoxide 5b to alkene 12
To a solution of NaI (1.35 g, 9 mmol) in dry acetonitrile (10 ml)
was added TMSCl (0.56 ml, 4.5 mmol) at rt and the mixture
was stirred at rt for a few minutes. To this mixture was added a
solution of the epoxide 5b (1.07 g, 3 mmol) in dry CH2Cl2 (5 ml)
at rt. After being stirred at rt for 30 min, the reaction mixture
was diluted with Et2O and washed successively with aq. 1%
Na2S2O3 and brine. Evaporation of the dried solvent gave a
residue, which was purified by SCC (acetone–hexane, 1 : 4) to
afford the alcohol (542 mg, 80%) as a colorless oil. To a solution
of the alcohol (542 mg, 2.4 mmol) in dry CH2Cl2 (5 ml) was
added Et3N (0.64 ml, 4.8 mmol), DMAP (586 mg, 4.8 mmol)
and a solution of TBSCl (433 mg, 2.9 mmol) in dry CH2Cl2
(3 ml) at rt and the mixture was stirred at rt for 15 h. The
reaction mixture was poured into ice–water and extracted with
Et2O. The extracts were washed successively with aq. 5% HCl,
saturated aq. NaHCO3 and brine. Evaporation of the dried
extracts gave a residue, which was purified by SCC (Et2O–
hexane, 1 : 9) to yield 12 (611 mg, 75%; 60% from 5b) as a
colorless oil. Spectral data of this compound were identical
with those of 12 derived from 11 in this paper.
Rearrangement of epoxide 5a by aminium salt 9
To a solution of the epoxide 5a (178 mg, 0.5 mmol) in CH2Cl2
(4 ml) was added aminium salt 98 (42 mg, 0.05 mmol) at rt and
the mixture was stirred at rt for 30 min. Evaporation of the
reaction mixture gave a residue, which was purified by SCC
3-[(1R,4S)-4-tert-Butyldimethylsilyloxy-1,2,2-trimethylcyclo-
pentyl]-3-{[(4-methoxyphenyl)methoxy]methoxy}propan-1-ol 15
To a suspension of LAH (24 mg, 0.64 mmol) in dry Et2O (5 ml)
was added dropwise a solution of 14 (323 mg, 0.64 mmol) in
dry Et2O (15 ml) at 0 ЊC. After being stirred at 0 ЊC for 30 min,
the excess of LAH was decomposed by dropwise addition of
water. The mixture was extracted with Et2O and the extracts
were washed successively with aq. 5% HCl, saturated aq.
NaHCO3 and brine. Evaporation of the dried solvent gave a
residue, which was purified by SCC (acetone–hexane, 1 : 9) to
(Et2O–hexane, 3 : 17
acetone–hexane, 1 : 5) to afford the
cyclopentyl compound 8 (112 mg, 63%) and the deprotected
compound 13 (36 mg, 30%) as colorless oils, respectively.
Cyclopentyl compound 8. [α]2D2 ϩ10.0 (c 1.00, MeOH); νmax
/
cmϪ1 1736 (OAc), 1699 (C᎐O); δ (300 MHz) 0.01 (6H, s,
᎐
H
SiMe2), 0.82 (3H, s, 1-Meα), 0.86 (9H, s, SiBut), 1.14 (3H, s,
1584
J. Chem. Soc., Perkin Trans. 1, 2002, 1581–1587

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afford the alcohol 15 (292 mg, 99%) as a colorless oil; νmax/cmϪ1
3465 (OH), 1613 and 1514 (Ph); δH (300 MHz) 0.01 (6H, s,
SiMe2), 0.86 (9H, s, SiBut), 0.92, 1.05 and 1.13 (each 3H, s,
gem-Me and 5-Me), 1.30 (1H, dd, J 14 and 2, 2-Hβ), 1.78 (4H,
m, 4-H2 and 7-H2), 1.98 (1H, dd, J 14 and 9, 2-Hα), 3.66 (1H, t,
J 5.5, 6-H), 3.77 (2H, m, 8-H2), 3.81 (3H, s, OMe), 4.23 (1H, m,
3-H), 4.52 and 4.68 (each 1H, d, J 11.5, CH2Ph), 4.81 and
4.87 (each 1H, d, J 6.5, –OCH2O–), 6.89 and 7.27 (each 2H, d,
J 8.5, Ar-H4) (Found: Mϩ, 466.3105. C26H46O5Si requires M,
466.3112).
(86 mg, 0.36 mmol). After being stirred at rt for 2 h, the reaction
mixture was filtered through Celite. Evaporation of the filtrate
gave a residue, which was purified by SCC (Et2O–hexane, 1 : 9)
to afford the alcohol 19 (133 mg, 88%) as a colorless oil; λmax
/
nm 228; νmax/cmϪ1 3558 (OH), 1659 (conj. C᎐O); δH (300 MHz)
᎐
0.01 and 0.11 (each 6H, s, SiMe2 × 2), 0.87 and 0.93 (each 9H, s,
SiBut × 2), 0.98, 1.10 and 1.11 (each 3H, s, gem-Me and 5-Me),
1.29 (1H, dd, J 14 and 2.5, 2-Hβ), 1.74 (3H, d, J 1, 9-Me), 1.78
(2H, d, J 7, 4-H2), 1.88 (1H, dd, J 13.5 and 9, 2-Hα), 2.73 (1H, s,
OH), 2.71 and 2.90 (each 1H, d-like, J 3, 7-H2), 4.04 (1H, m,
6-H), 4.25 (1H, m, 3-H), 4.42 (2H, br d, J 5, 11-H2), 6.64 (1H,
td-like, J 5 and 1, 10-H) (Found: Mϩ, 498.3531. C27H54O4Si2
requires M, 498.3557).
3-[(1R,4S)-4-tert-Butyldimethylsilyloxy-1,2,2-trimethylcyclo-
pentyl]-3-{[(4-methoxyphenyl)methoxy]methoxy}propanal 16
To a solution of the alcohol 15 (125 mg, 0.27 mmol) in DMSO
(1 ml) was added a solution of IBX12 (188 mg, 0.67 mmol) in
DMSO (0.67 ml) at rt and the mixture was stirred at rt for 1 h.
The reaction mixture was diluted with water (5 ml) and the
white precipitate was filtered. The filtrate was extracted with
Et2O. Standard work-up gave a residue, which was purified by
SCC (acetone–hexane, 1 : 9) to provide the aldehyde 16 (116
mg, 93%) as a colorless oil; νmax/cmϪ1 1721 (CHO), 1613 and
1514 (Ph); δH (300 MHz) 0.01 (6H, s, SiMe2), 0.86 (9H, s, SiBut),
0.93, 1.06 and 1.12 (each 3H, s, gem-Me and 5-Me), 1.23
(1H, dd, J 13.5 and 2.5, 2-Hβ), 1.80 (2H, d, J 7.5, 4-H2), 1.92
(1H, dd, J 13.5 and 8.5, 2-Hα), 2.37 (1H, dd, J 17 and 2.5, 7-H),
2.78 (1H, ddd, J 17, 7 and 2, 7-H), 3.80 (3H, s, OMe), 4.13 (1H,
dd, J 7 and 2.5, 6-H), 4.24 (1H, m, 3-H), 4.42 and 4.54 (each
1H, d, J 11.5, CH2Ph), 4.70 and 4.76 (each 1H, d, J 7,
–OCH2O–), 6.87 and 7.23 (each 2H, d, J 8.5, Ar-H4), 9.76 (1H,
d, J 2, CHO) (Found: Mϩ, 464.2967. C26H44O5Si requires M,
464.2960).
Oxidation of the ꢀ-hydroxy ketone 19
To a solution of the alcohol 19 (200 mg, 0.40 mmol) in dry
DMSO (14 ml) was added Ac2O (7 ml) at rt and the mixture was
stirred at rt for 16 h. The reaction mixture was poured into ice-
water and extracted with Et2O. The extracts were washed with
water and saturated aq. NaHCO3 and brine. Evaporation of
the dried solvent gave a residue, which was purified by SCC
(Et2O–hexane, 1 : 19) to afford the conjugated β-diketone 20
(71 mg, 36%) and the acetate 21 (72 mg, 33%) as colorless oils,
respectively.
(2E,4E )-6-tert-Butyldimethylsilyloxy-1-[(1R,4S)-4-tert-
butyldimethylsilyloxy-1,2,2-trimethylcyclopentyl]-3-hydroxy-4-
methylhexa-2,4-dienone 20. [α]2D3 Ϫ23.4 (c 0.47, CHCl3); λmax/nm
305; νmax/cmϪ1 1583 (hydrogen-bonded conj. C᎐O); δ (300
MHz) 0.03 and 0.09 (each 6H, s, SiMe2 × 2), 0.81 (3H, s,
1-Meα), 0.88 and 0.92 (each 9H, s, SiBut × 2), 1.15 (3H, s,
1-Meβ), 1.30 (3H, s, 5-Me), 1.51 (1H, dd, J 14 and 2.5, 4-Hβ),
1.69 (1H, dd, J 13.5 and 4.5, 2-Hβ), 1.80 (3H, d, J 1, 9-Me), 1.98
(1H, dd, J 13.5 and 7.5, 2-Hα), 2.73 (1H, dd, J 14 and 8, 4-Hα),
4.38 (1H, m, 3-H), 4.39 (2H, d, J 6, 11-H2), 5.81 (1H, s, 7-H),
6.59 (1H, t, J 6, 10-H), 16.15 (1H, s, enolic OH) (Found: Mϩ,
496.3412. C27H52O4Si2 requires M, 496.3407).
᎐
H
(4E )-6-tert-Butyldimethylsilyloxy-1-[(1R,4S)-4-tert-butyl-
dimethylsilyloxy-1,2,2-trimethylcyclopentyl]-1-{[(4-methoxy-
phenyl)methoxy]methoxy}-4-methylhex-4-en-3-one 18
To a solution of the vinyl bromide 1713 (403 mg, 1.52 mmol) in
dry Et2O (4 ml) was added ButLi (1.64 M in pentane; 0.93 ml,
1.52 mmol) at Ϫ78 ЊC and the mixture was stirred at Ϫ78 ЊC for
10 min. A solution of the aldehyde 16 (235 mg, 0.51 mmol) in
dry Et2O (6 ml) was added to this mixture at Ϫ78 ЊC for 1 h.
After being quenched with saturated aq. NH4Cl, the mixture
was extracted with Et2O. Standard work-up gave a residue,
which was purified by SCC (Et2O–hexane, 1 : 4) to afford the
adduct (313 mg, 95%) as a colorless oil. Then, to a solution of
the adduct (313 mg, 0.48 mmol) in DMSO (1.5 ml) was added a
solution of IBX12 (337 mg, 1.20 mmol) in DMSO (1.2 ml) at rt
and the mixture was stirred at rt for 16 h. The reaction mixture
was diluted with water (5 ml) and the white precipitate was
filtered. The filtrate was extracted with Et2O. Standard work-up
gave a residue, which was purified by SCC (Et2O–hexane, 3 : 17)
to provide the conjugated ketone 18 (197 mg, 63%; 60% from
(4E )-1-Acetyloxy-6-tert-butyldimethylsilyloxy-1-[(1R,4S)-4-
tert-butyldimethylsilyloxy-1,2,2-trimethylcyclopentyl]-4-methyl-
hex-4-en-3-one 21. [α]2D7 ϩ10.0 (c 0.40, MeOH); λmax/nm 231;
νmax/cmϪ1 1668 (conj. C᎐O); δH (300 MHz) 0.02 and 0.11 (each
᎐
6H, s, SiMe2 × 2), 0.85 and 0.93 (each 9H, s, SiBut × 2), 0.99,
1.07 and 1.13 (each 3H, s, gem-Me and 5-Me), 1.16 (1H, m,
2-Hβ), 1.76 (3H, d, J 1, 9-Me), 1.78 (2H, d, J 8, 4-H2), 1.93 (1H,
dd, J 14 and 9, 2-Hα), 2.14 (3H, s, OAc), 2.59 (1H, dd, J 17.5
and 2.5, 7-H), 3.07 (1H, dd, J 17.5 and 6.5, 7-H), 4.23 (2H, m,
3-H and 6-H), 4.42 (2H, d, J 5, 11-H2), 6.66 (1H, td-like, J 5 and
1, 10-H) [Found: (M Ϫ Ac)ϩ, 497.3463. C27H53O4Si2 requires M
Ϫ Ac, 497.3485].
(2E,4E )-3-Acetyloxy-6-tert-butyldimethylsilyloxy-1-[(1R,4S)-
4-tert-butyldimethylsilyloxy-1,2,2-trimethylcyclopentyl]-4-
methylhexa-2,4-dienone 22
16) as a colorless oil; νmax/cmϪ1 1669 (conj. C᎐O), 1613 and 1514
᎐
(Ph); δH (300 MHz) Ϫ0.02 and 0.09 (each 6H, s, SiMe2 × 2),
0.86 and 0.92 (each 9H, s, SiBut × 2), 0.96, 1.06 and 1.16 (each
3H, s, gem-Me and 5-Me), 1.18 (1H, m, 2-Hβ), 1.63 (3H, d, J 1,
9-Me), 1.79 (2H, d, J 7, 4-H2), 1.92 (1H, dd, J 14 and 9, 2-Hα),
2.45 (1H, dd, J 17 and 2, 7-H), 3.16 (1H, dd, J 17 and 7, 7-H),
3.79 (3H, s, OMe), 4.26 (4H, m, 3-H, 6-H and 11-H2), 4.38 and
4.65 (each 1H, d, J 12, CH2Ph), 4.62 and 4.65 (each 1H, d, J 6.5,
–OCH2O–), 6.53 (1H, tq-like, J 5 and 1, 10-H), 6.83 and 7.17
(each 2H, d, J 9, Ar-H4) (Found: Mϩ, 648.4236. C36H64O6Si2
requires M, 648.4244).
Ac2O (0.5 ml) was added to a solution of the β-diketone 20
(104 mg, 0.21 mmol), Et3N (0.04 ml, 0.29 mmol) and DMAP
(28 mg, 0.23 mmol) in dry CH2Cl2 (1 ml) at rt. After being
stirred at rt for 30 min, the mixture was poured into ice–water
and extracted with Et2O. The extracts were washed successively
with aq. 5% HCl, saturated aq. NaHCO3 and brine. Evapor-
ation of the dried extracts gave a residue, which was purified by
SCC (Et2O–hexane, 1 : 4) to afford the enol acetate 22 (104 mg,
92%) as a colorless oil; [α]2D0 Ϫ10.3 (c 0.98, CHCl3); λmax/nm 277;
νmax/cmϪ1 1766 (OAc), 1673 (conj. C᎐O), 1586 (conj. C᎐C);
δH (300 MHz) 0.01 and 0.07 (each 6H, s, SiMe2 × 2), 0.86 and
0.90 (each 9H, s, SiBut × 2), 0.82, 1.16 and 1.31 (each 3H, s,
gem-Me and 5-Me), 1.42 (1H, m, 4-Hβ), 1.68 (1H, dd, J 13 and
5, 2-Hβ), 1.80 (3H, d, J 1, 9-Me), 1.88 (1H, dd, J 13 and 7.5,
2-H), 2.31 (3H, s, OAc), 2.78 (1H, m, 4-Hα), 4.33 (1H, m, 3-H),
᎐
᎐
(4E )-6-tert-Butyldimethylsilyloxy-1-[(1R,4S)-4-tert-butyl-
dimethylsilyloxy-1,2,2-trimethylcyclopentyl]-1-hydroxy-4-
methylhex-4-en-3-one 19
To a solution of the ketone 18 (197 mg, 0.30 mmol) dissolved in
a mixture of CH2Cl2–H2O (18 : 1, 6.54 ml) was added DDQ11b
J. Chem. Soc., Perkin Trans. 1, 2002, 1581–1587
1585

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4.38 (2H, d, J 5.5, 11-H2), 6.20 (1H, m, 10-H), 6.25 (1H, s, 7-H)
(Found: Mϩ, 538.3509. C29H54O5Si2 requires M, 538.3512).
(acetone–hexane, 1 : 4) to afford an isomeric mixture of apoc-
arotenal 26 (12 mg, 92%) in which the main product was all-E
isomer. Purification of a part of the isomeric mixture by PTLC
(acetone–hexane, 3 : 7) provided the all-E isomer as an orange
solid; λmax/nm 419 and 440(sh); νmax/cmϪ1 3610 and 3476 (OH),
(2E,4E )-3-Acetyloxy-1-[(1R,4S)-4-tert-butyldimethylsilyloxy-
1,2,2-trimethylcyclopentyl]-6-hydroxy-4-methylhexa-2,4-dienone
23
1665 (conj. CHO), 1605 and 1568 (conj. C᎐C or hydrogen-
᎐
bonded conj. C᎐O); δ (300 MHz) 0.85 (3H, s, 1-Meα), 1.19
᎐
H
A solution of TBAF (1 M in THF; 0.19 ml, 0.19 mmol) was
added to a solution of the acetate 22 (104 mg, 0.19 mmol) in
dry THF (4 ml) at 0 ЊC and the mixture was stirred at 0 ЊC for
1 h. The reaction mixture was diluted with Et2O. Standard
work-up gave a residue, which was purified by SCC (Et2O–
(3H, s, 1-Meβ), 1.35 (3H, s, 5-Me), 1.55 (1H, dd, J 14.5 and 3,
4-Hβ), 1.72 (1H, dd, J 13.5 and 4, 2-Hβ), 1.90 (3H, s, 13Ј-Me),
2.00 (3H, s, 9-Me), 2.06 (3H, s, 13-Me), 2.09 (1H, dd, J 13.5 and
8, 2-Hα), 2.88 (1H, dd, J 14.5 and 8.5, 4-Hα), 4.53 (1H, m, 3-H),
5.87 (1H, s, 7-H), 6.41 (1H, d, J 11.5, 14-H), 6.65 (1H, d, J 15,
12-H), 6.74 (1H, dd, J 15 and 10.5, 11-H), 6.77 (1H, dd, J 14.5
and 11.5, 15Ј-H), 6.97 (1H, d, J 11.5, 14Ј-H), 7.03 (1H, dd,
J 14.5 and 11.5, 15-H), 7.23 (1H, d, J 10.5, 10-H), 9.48 (1H, s,
12Ј-H) (Found: Mϩ, 398.2439. C25H34O4 requires M, 398.2458).
hexane, 1 : 4
acetone–hexane, 1 : 4) to afford the alcohol 23
(75 mg, 92%) as a colorless oil; [α]2D4 ϩ0.98 (c 1.02, CHCl3);
λmax/nm 277; νmax/cmϪ1 3604 and 3508 (OH), 1767 (OAc), 1674
(conj. C᎐O), 1587 (conj. C᎐C); δ (300 MHz) 0.01 (6H, s,
᎐
᎐
H
SiMe2), 0.86 (9H, s, SiBut), 0.82 and 1.16 (each 3H, s, gem-Me),
1.31 (3H, s, 5-Me), 1.42 (1H, m, 4-Hβ), 1.68 (1H, dd, J 14 and 5,
2-Hβ), 1.85 (3H, s, 9-Me), 1.87 (1H, m, 2-Hα), 2.31 (3H, s, OAc),
2.78 (1H, m, 4-Hα), 4.33 (1H, m, 3-H), 4.38 (2H, d, J 6, 11-H2),
6.25 (1H, m, 10-H), 6.28 (1H, s, 7-H) (Found: Mϩ, 424.2632.
C23H40O5Si requires M, 424.2647).
Synthesis of mytiloxanthin
A basic solution (3 ml) of KOH (500 mg) dissolved in water
(1 ml) and propan-2-ol (10 ml) was added dropwise to a
solution of the apocarotenal 26 (11.7 mg, 0.03 mmol) and the
Wittig salt 2715 (61 mg, 0.12 mmol) in propan-2-ol (6 ml) at
0 ЊC. After being stirred at 0 ЊC for 30 min, the reaction mixture
was extracted with Et2O and washed with saturated aq. NH4Cl
and brine. Evaporation of the dried extracts gave a residue,
which was purified by SCC (acetone–hexane, 3 : 7) to afford an
isomeric mixture of mytiloxanthin (5.2 mg, 30%). Purification
of a part of the isomeric mixture by PHPLC [CHEMCOSORB
7ODS-H 1.0 × 30 cm; H2O–MeOH, 4 : 96; 460 nm detect.]
provided the all-E isomer 1, 9Z one 28 and 9Z,11Z one 29 as
red solids respectively, in a pure state. Spectral properties of the
synthetic all-E isomer 1 and 9Z one 28 were in agreement with
those of a natural specimen.4
(2E,4E )-4-Acetyloxy-6-[(1R,4S)-4-hydroxy-1,2,2-trimethyl-
cyclopentyl]-3-methyl-6-oxohexa-2,4-dienal 10b
To a solution of the alcohol 23 (54 mg, 0.13 mmol) in DMSO
(0.25 ml) was added a solution of IBX12 (72 mg, 0.26 mmol) in
DMSO (0.26 ml) at rt and the mixture was stirred at rt for 1 h.
The reaction mixture was diluted with water (3 ml) and the
white precipitate was filtered. The filtrate was extracted with
Et2O. Standard work-up gave a residue, which was purified by
SCC (acetone–hexane, 3 : 17) to afford the aldehyde (33 mg,
60%) as a pale yellow oil. A mixture of 47% aq HF–CH3CN
(1 : 19; 0.4 ml) was added to a solution of this aldehyde (33 mg,
0.08 mmol) in a mixture of CH3CN–THF (9 : 1; 4 ml) at rt.
After being stirred at rt for 1.5 h, the reaction mixture was
quenched with saturated aq. NaHCO3 and extracted with Et2O.
Standard work-up gave a residue, which was purified by SCC
(acetone–hexane, 3 : 7) to provide the desilylated aldehyde 10b
(22 mg, 92%; 55% from 23) as a pale yellow oil; [α]2D6 Ϫ10.0
(c 0.40, CHCl3); λmax/nm 283; νmax/cmϪ1 3611 and 3476 (OH),
all-E Isomer 1. CD (Et2O)/nm (∆ε) 230 (Ϫ0.5), 275 (0), 294
(ϩ0.7), 310 (0), 360 (Ϫ0.3); λmax/nm 470, λmax(Et2O)/nm 467;
νmax/cmϪ1 3530 and 3321 (OH), 1602 (hydrogen-bonded conj.
C᎐O); δH (500 MHz) 0.85 (3H, s, 1Ј-Meα), 1.14 (3H, s, 1-Meax),
᎐
1.19 (3H, s, 1Ј-Meβ), 1.20 (3H, s, 1-Meeq), 1.35 (3H, s, 5Ј-Me),
1.45 (1H, t, J 11.5, 2-Hax), 1.55 (1H, m, 4Ј-Hβ), 1.71 (1H, dd,
J 13.5 and 4, 2Ј-Hβ), 1.83 (1H, m, 2-Heq), 1.92 (3H, s, 5-Me),
1.98 (6H, s, 13-Me and 13Ј-Me), 1.99 (3H, s, 9Ј-Me), 2.01 (3H,
s, 9-Me), 2.07 (1H, m, 4-Hax), 2.09 (1H, dd, J 13.5 and 8, 2Ј-Hα),
2.43 (1H, br dd, J 18 and 5.5, 4-Heq), 2.88 (1H, dd, J 14.5 and 9,
4Ј-Hα), 4.00 (1H, m, 3-H), 4.52 (1H, m, 3Ј-H), 5.86 (1H, s,
7Ј-H), 6.28 (1H, d, J 11.5, 14-H), 6.36 (1H, d, J 15, 12-H), 6.38
(1H, d, J 10.5, 14Ј-H), 6.46 (1H, d, J 11.5, 10-H), 6.55 (1H, dd,
J 15 and 11.5, 11-H), 6.60 (1H, dd, J 15 and 10.5, 11Ј-H), 6.64
(1H, dd, J 14 and 11, 15Ј-H), 6.65 (1H, d, J 15.5, 12Ј-H), 6.71
(1H, dd, J 14 and 11.5, 15-H), 7.23 (1H, d, J 10.5, 10Ј-H)
(Found: Mϩ, 598.4016. C40H54O4 requires M, 598.4025).
1773 (OAc), 1674 (conj. C᎐O and conj. CHO), 1588 (conj.
᎐
C᎐C); δ (300 MHz) 0.84 (3H, s, 1-Meα), 1.19 (3H, s, 1-Meβ),
᎐
H
1.35 (3H, s, 5-Me), 1.46 (1H, dd, J 14.5 and 3, 4-Hβ), 1.70 (1H,
dd, J 14 and 5, 2-Hβ), 1.96 (1H, dd, J 14 and 8, 2-Hα), 2.31 and
2.33 (each 3H, s, 9-Me and OAc), 2.85 (1H, dd, J 14.5 and 8.5,
4-Hα), 4.47 (1H, m, 3-H), 6.37 (1H, d, J 7.5, 10-H), 6.60 (1H,
s, 7-H), 10.17 (1H, d, J 7.5, 11-H) (Found: Mϩ, 308.1648.
C17H24O5 requires M, 308.1625).
(2E,4E,6E,8E,10E,12E )-12-Hydroxy-14-[(1R,4S)-4-hydroxy-
1,2,2-trimethylcyclopentyl]-2,7,11-trimethyl-14-oxotetradeca-
2,4,6,8,10,12-hexaenal 26
9Z-Isomer 28. CD (Et2O)/nm (∆ε) 230 (Ϫ0.8), 247 (0), 258
(ϩ1.0), 280 (0), 300 (Ϫ0.3), 310 (0), 350 (ϩ1.0), 370 (0); λmax/nm
467, 358 λmax(Et2O)/nm 465, 358; νmax/cmϪ1 3530 and 3321
An acidic solution (0.1 ml) prepared from PTSA (500 mg) and
H3PO4 (725 mg) in MeOH (37.5 ml) and trimethyl orthofor-
mate (0.1 ml, 0.91 mmol) were added to a solution of the Wittig
salt 2414 (35.6 mg, 0.08 mmol) in MeOH (1 ml). The mixture
was stirred at rt for 1 h and neutralized with NaOMe (1 M in
MeOH) until just before the red color of an ylide appeared.
Evaporation of the solvent provided the Wittig salt 25, to which
a solution of the aldehyde 10b (9.8 mg, 0.03 mmol) in propan-2-
ol (1.5 ml) was added. To the mixture, a basic solution (1 ml)
of KOH (500 mg) dissolved in water (1 ml) and propan-2-ol
(10 ml) was added dropwise at 0 ЊC. After being stirred at 0 ЊC
for 1 h, the mixture was poured into ice–water, and extracted
with Et2O. The extracts were shaken with aq. 5% HCl until the
fine structure disappeared on UV–VIS, washed successively
with saturated aq. NaHCO3 and brine. Evaporation of the
dried extracts provided a residue, which was purified by SCC
(OH), 1602 (hydrogen-bonded conj. C᎐O); δ (500 MHz) 0.85
᎐
H
(3H, s, 1Ј-Meα), 1.19 (6H, s, 1-Meax and 1Ј-Meβ), 1.26 (3H, s,
1-Meeq), 1.35 (3H, s, 5Ј-Me), 1.48 (1H, t, J 12, 2-Hax), 1.56 (1H,
m, 4Ј-Hβ), 1.72 (1H, dd, J 13.5 and 4.5, 2Ј-Hβ), 1.93 (1H, ddd,
J 11.5, 3 and 2, 2-Heq), 1.95 (3H, s, 13-Me), 1.97 (6H, s, 5-Me
and 9Ј-Me), 1.99 (3H, s, 13Ј-Me), 2.01 (3H, s, 9-Me), 2.09 (1H,
dd, J 14 and 8, 2Ј-Hα), 2.10 (1H, m, 4-Hax), 2.46 (1H, br dd,
J 17.5 and 4.5, 4-Heq), 2.88 (1H, dd, J 14.5 and 9, 4Ј-Hα), 4.01
(1H, m, 3-H), 4.53 (1H, m, 3Ј-H), 5.86 (1H, s, 7Ј-H), 6.27 (1H,
d, J 11, 14-H), 6.30 (1H, d, J 11.5, 10-H), 6.35 (1H, d, J 15.5,
12-H), 6.37 (1H, d, J 10.5, 14Ј-H), 6.63 (1H, dd, J 15.5 and 12,
15Ј-H), 6.64 (1H, dd, J 15 and 10.5, 11Ј-H), 6.65 (1H, d, J 15,
12Ј-H), 6.71 (1H, dd, J 14 and 11, 15-H), 6.87 (1H, dd, J 15 and
11, 11-H), 7.23 (1H, d, J 10.5, 10Ј-H) (the cross peak was
1586
J. Chem. Soc., Perkin Trans. 1, 2002, 1581–1587

View Article Online
observed between 11-H and 5-Me in the NOESY spectrum)
References
(Found: Mϩ, 598.4001. C40H34O4 requires M, 598.4025).
1 Part 7: C. Tode, Y. Yamano and M. Ito, J. Chem. Soc., Perkin Trans.
1, 2001, 3338.
2 B. T. Scheer, J. Biol. Chem., 1940, 136, 275.
9Z,11Z-Isomer 29. λmax/nm 463 and 296, λmax(Et2O)/nm 460,
447, 294; νmax/cmϪ1 3530 and 3321 (OH), 1602 (hydrogen-
bonded conj. C᎐O); δ (500 MHz) 0.83 (3H, s, 1Ј-Meα), 1.15
3 (a) A. K. Chopra, G. P. Moss and B. C. L. Weedon, J. Chem. Soc.,
Chem. Commun., 1977, 467; (b) A. K. Chopra, A. Khare, G. P. Moss
and B. C. L. Weedon, J. Chem. Soc., Perkin Trans. 1, 1988, 1383;
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1996, 1337; (b) Y. Yamano, C. Tode and M. Ito, J. Chem. Soc.,
Perkin Trans. 1, 1998, 2569.
6 C. Tode, Y. Yamano and M. Ito, J. Chem. Soc., Perkin Trans. 1, 1999,
1625.
7 C. Tode, Y. Yamano and M. Ito, Chem. Pharm. Bull., 2000, 48, 1833.
8 L. Lopez, G. Mele, V. Fiandanese, C. Cardellicchio and A. Nacci,
Tetrahedron, 1994, 50, 9097.
9 Y. Yamano and M. Ito, J. Chem. Soc., Perkin Trans. 1, 1993, 1599.
10 R. Caputo, L. Mangoni, O. Neri and G. Palumbo, Tetrahedron Lett.,
1981, 22, 3551.
11 (a) T. Benneche, P. Strande and K. Undheim, Synthesis, 1983, 762;
(b) A. P. Kozikowski and J.-P. Wu, Tetrahedron Lett., 1987, 28, 5125.
12 M. Frigerio, M. Santagostino, S. Sputore and G. Palmisano,
J. Org. Chem., 1995, 60, 7272.
᎐
H
(3H, s, 1-Meax), 1.17 (3H, s, 1Ј-Meβ), 1.21 (3H, s, 1-Meeq), 1.33
(3H, s, 5Ј-Me), 1.45 (1H, t, J 12, 2-Hax), 1.56 (1H, m, 4Ј-Hβ),
1.70 (1H, dd, J 14 and 5, 2Ј-Hβ), 1.83 (1H, m, 2-Heq), 1.93 (3H,
s, 5-Me), 1.96 (3H, s, 9Ј-Me), 1.97 (3H, s, 13Ј-Me), 2.01 (3H, s,
9-Me), 2.05 (1H, m, 4-Hax), 2.07 (1H, dd, J 13.5 and 8, 2Ј-Hα),
2.08 (3H, s, 13-Me), 2.43 (1H, br dd, J 17 and 5.5, 4-Heq), 2.86
(1H, dd, J 14.5 and 8.5, 4Ј-Hα), 3.99 (1H, m, 3-H), 4.51 (1H, m,
3Ј-H), 5.84 (1H, s, 7Ј-H), 5.95 (1H, d, J 12.5, 12-H), 6.27 (1H,
d, J 10, 14-H), 6.36 (1H, d, J 10.5, 14Ј-H), 6.50 (1H, t, J 12.5,
11-H), 6.58 (1H, dd, J 15 and 10.5, 11Ј-H), 6.61 (1H, dd, J 15
and 10.5, 15Ј-H), 6.63 (1H, d, J 15, 12Ј-H), 6.66 (1H, dd, J 15
and 10.5, 15-H), 6.78 (1H, d, J 12.5, 10-H), 7.21 (1H, d, J 10.5,
10Ј-H) (the cross peak was observed between 11-H and 12-H
in the NOESY spectrum) (Found: Mϩ, 598.4018. C40H54O4
requires M, 598.4025).
13 (a) M. Schlosser and E. Hammer, Helv. Chim. Acta, 1974, 57, 2547;
(b) A. R. de Lera, B. Iglesias, J. Rodríguez, R. Alvarez, S. López,
X. Villanueva and E. Padrós, J. Am. Chem. Soc., 1995, 117, 8220.
14 K. Bernhard, F. Kienzle, H. Mayer and R. K. Müller, Helv. Chim.
Acta, 1980, 63, 1473.
15 E. Widmer, M. Soukup, R. Zell, E. Broger, H. P. Wagner and
M. Imfeld, Helv. Chim. Acta, 1990, 73, 861.
Acknowledgements
We thank Dr T. Maoka, Kyoto Pharmaceutical University for
his kind gift of spectral data on natural mytiloxanthins. We are
also grateful for the chemical support from Drs U. Hengartner
and K. Bernherd, Hoffmann-La Roche Ltd., Basel,
Switzerland.
16 Y. Yamano, C. Tode and M. Ito, J. Chem. Soc., Perkin Trans. 1, 1995,
1895.
J. Chem. Soc., Perkin Trans. 1, 2002, 1581–1587
1587