metadata|FILENOb201228fFILENO||PAPERTYPEarticlePAPERTYPE||JOURNAL|NAMEP1NAME||YEAR2002YEAR||VOLUMEVOLUME||ISSUE13ISSUE||PAGES1581-1587PAGES|JOURNAL|
titleCarotenoids and related polyenes. Part 8. Total synthesis of optically active mytiloxanthin applying the stereoselective rearrangement of tetrasubstituted epoxide|XREFXREF|
authorList|AUTHOR|NAMEChisato|SURNAMETodeSURNAME|NAME|AUTHOR||AUTHOR|NAMEYumiko|SURNAMEYamanoSURNAME|NAME|AUTHOR||AUTHOR|NAMEMasayoshi|SURNAMEItoSURNAME|NAME|AUTHOR|
abstractBiomimetic synthesis of {chem1} was accomplished with stereoselective rearrangement of the tetrasubstituted epoxide {chem5} as a key reaction. This is the first total synthesis of optically active all-E mytiloxanthin {chem1}.
body
introduction
{chem1}, with a unique cyclopentyl enolic [beta]-diketone group conjugated to a polyene chain, was first isolated from Mytilus californianus by Scheer in 1940.2 Its structure and synthesis of the 9Z-isomer were reported by Weedon's group,3 they developed the new synthetic route to polyene [beta]-diketones using Claisen type condensation between polyene esters and methyl ketones. The absolute configuration was determined by Maoka and Fujiwara in 1996. The cyclopentyl end group of mytiloxanthin {chem1} is believed to be formed in Nature from the epoxide end group of 5,6-epoxy carotenoids such as halocynthiaxanthin {chem2} by cleavage of the oxirane ring at the C-5 position and successive ring contraction (a pinacolic rearrangement) (Scheme 1, route a).
We found5 that the acyclic-tetrasubstituted olefinic compounds and the cyclopentyl ketone were derived by Lewis acid-promoted stereoselective rearrangement of epoxy compounds. Then, the biomimetic total synthesis of crassostreaxanthin B {chem3} possessing the acyclic-tetrasubstituted olefinic end group was achieved using this rearrangement reaction.
In a previous communication,7 we reported the first total synthesis of {chem1} which includes the new construction of conjugated {chem10a chem10b} through the cyclopentyl compound {chem8} (Scheme 2), prepared by application of the stereoselective rearrangement of epoxide {chem5}. The present paper is concerned with a full account of the experiments.
results
It has been previously reported5b that OEt2-treatment of the epoxide {chem4} (Scheme 2) with the acetoxy ethylgroup at the C-6 position resulted in a very slow reaction and in a low-yieldformation of the C-5 diastereomer {chem6} instead of the desired compound {chem7}. Efficient preparation of {chem7} was obtained from the investigation of other Lewis acids with an aminium salt. Thus, treatment of the epoxide {chem4} with tris(4-bromophenyl)aminium hexachloroantimonate {chem9} in CH2Cl2was found toafford {chem7}in reasonableyield(69%) (Scheme 2). In order to accomplish the biomimetic synthesis of {chem1} in an analogous manner to the successful synthesis of {chem3}, the acetoxy group at the C-3 position in {chem4} was replaced by the tert-butyldimethylsilyl (TBS) ether leading to epoxide {chem5}. The synthetic route of mytiloxanthin {chem1} was therefore planned through conversion of {chem5} to the cyclopentyl ketone {chem8} and subsequent construction of enolic [beta]-diketone as shown in Scheme 2.
Starting from the previously prepared optically active 1 {chem11}(Scheme 3), acetylation followed by epoxidation with MCPBAgave {chem5a chem5b} (
balancedBrackets{chem5a}: 26% from {chem11}; {chem5b}: 48% from {chem11}
), in which the relative configurations between the silyloxy and epoxy groups were confirmed by 1H NMR.9 The undesired isomer {chem5b} was returned to the tetrasubstituted olefin {chem12} by the following deepoxidation procedure. Treatment of {chem5b} with TMSCl and NaI in dry acetonitrilefollowed by silylationgave {chem12} in 60% yield. Reaction of anti-epoxide {chem5a} with aminium salt {chem9}ACTION providedcml:provide the desired cyclopentyl compound {chem8} (63%) and its deprotected alcohol {chem13}(30%) which was easily resilylated togive {chem8} (89%). Consequently, the cyclopentyl ketone {chem8} was synthesized by the stereoselective rearrangement of {chem5a} in high yield. The structure of {chem8} was determined from the following spectral data. Its IR absorption showed a new carbonyl frequency at 1699 cm-1. In its 1H NMR spectrum, the methylene signal of the C-7 position appeared at [delta] 2.75 (t), further downfield than the corresponding signal [[delta] 2.01 (2H, m)] of {chem5a}, in addition, proton signals on the cyclopentane ring were observed analogous to results reported previously.
Reduction of {chem8} with NaBH4 followed by protection of the resulting hydroxy group with p-methoxybenzyloxymethyl (PMBM) chloridegave compound {chem14} (62% from {chem8}
rbracket
), which was reduced with LAH toACTION providecml:providethe alcohol {chem15} (99%). This was subjected to oxidation with o-iodoxybenzoic acid(IBX) toyieldthe aldehyde {chem16} (93%), which was reacted with vinyllithium prepared from the vinyl bromide {chem17} and ButLi followed by oxidation with IBX toACTION providecml:providethe ketone {chem18} (60% from {chem16}
rbracket
). Its structure was confirmed by IR ([nu] 1669 cm-1) and 1H NMR data [[delta] 6.53 (1H, tq-like, J 5, 1, 10-H), 4.26 (2H, m, 11-H2
rbracket
)]. Deprotection of the PMBM group in {chem18} with DDQgave the alcohol {chem19} (88%), which was treated with DMSO and Ac2Otoafford the enolic [beta]-diketone {chem20} (36%) and the acetate {chem21} (33%). Attempts to prepare {chem20} from {chem19} under other oxidation conditions (e.g., DMSO-oxalyl chloride, DMSO-TFAA, DMSO-SO3·Py, NMO-TPAP and IBX) wereunsuccessful. The 1H NMR spectrum of {chem20} had a broad one-proton signal at [delta] 16.15 and a sharp one-proton resonance at [delta] 5.81. In addition, its IR spectrum showed an absorption at 1583 cm-1 exhibiting the presence of a strongly hydrogen-bonded carbonyl group. These spectral data confirmed the presence of a completely enolic [beta]-diketone structure. The structure of {chem21} was revealed by the following 1H NMR data [an acetoxy methyl signal appeared at [delta] 2.14 (3H, s) and a proton signal ([delta] 4.23) due to C-6 shifted downfield compared to the corresponding signal ([delta] 4.04) of {chem19}].
Unfortunately, direct conversion of {chem20} into the {chem10a} (Scheme 2) by deprotection of the allylic TBS group and subsequent oxidation of the resulting alcohol using several reagents (IBX, MnO2, etc.) wasunsuccessful, probably due to the instability of the [beta]-diketone part. Thus, after protection of the [beta]-diketone moiety in {chem20} by acetylation, the resulting acetate {chem22}was partly deprotected with TBAF togive the allylic alcohol {chem23} (92%) which was oxidized with IBX followed by removal of another TBS group with HFtoafford the C15-aldehyde {chem10b} (55% from {chem23}
rbracket
) 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 ([delta] 10.17, d, J 7.5) and 10-H ([delta] 6.37, d, J 7.5).
The Wittig reaction of {chem10b} with the salt {chem25} in the presence of KOHas a base in a{mixture} of water and propan-2-olgave condensed products which, after acidhydrolysis,ACTION providedcml:provide an isomeric{mixture} of C25-apocarotenals {chem26} (92% from {chem10b}
rbracket
). Investigations of alternative conditions (e.g., NaOMe-MeOH, BunLi-CH2Cl2-THF) for optimization of this condition resulted in the formation of an unexpected complex{mixture}. This is presumably owing to the presence of the conjugated [beta]-diketone moiety in the molecule. It was notable that KOH was the best base in the condensation of the conjugated polyenes including the [beta]-diketonepart. Finally, the isomeric{mixture} {chem26} was condensed with the acetylenic C15-Wittig salt {chem27} in the presence of KOH in propan-2-olat 0 °C toyieldthe products (30%), a part of whichwas separated by repeated preparative HPLC (PHPLC) in the dark toafford all-E mytiloxanthin {chem1}, 9Z-isomer {chem28}, 9Z,11Z-one {chem29} and unidentified isomers. Three isomers (
balancedBrackets{chem1}, {chem28} and {chem29}
) were respectively obtained in pure form (all-E {chem1}-9Z {chem28}-9Z,11Z {chem29} = 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 configurations were confirmed from 2D-nuclear Overhauser enhancement spectroscopy (NOESY) experiments in 1H NMR spectra (see Experimental section). 9Z,11Z-Stereochemistry in {chem29} was determined by 1H NMR data in comparison with those16 of 9'Z,11'Z-isomer of halocynthiaxanthin {chem2} skeletal compound. This is the first biomimetic total synthesis of optically active all-E mytiloxanthin {chem1} by application of the stereoselective rearrangement of the epoxide {chem5a} with aminium salt {chem9}.
experimental
UV-VIS spectra were recorded on a JASCO Ubest-55 instrument for ethanolsolution s unless otherwise stated. IR spectra were measured on a Perkin Elmer FT-IR spectrometer, model Paragon 1000, for chloroformsolution s. 1H 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 deuteriochloroformsolution s (
lbracket
tetramethylsilane as internal reference). J-Values aregiven in Hz. NMR assignments aregiven using the carotenoid numbering system. Mass spectra were taken on a Hitachi M-4100 spectrometer. Optical rotations were measured on a JASCO DIP-181 polarimeter ([[alpha]]D-values are in units of 10-1 deg cm2 g-1). CD spectra were measured on a Shimadzu-AVIV 62A DS circular dichroism spectrometer.
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 [osc:solidstate=plates ] (Merck silica gel 60F254 precoated [osc:solidstate=plates ], [osc:conc=0.5(oscUnits:unknown) ] thickness). Low-pressure CC was performed on a Yamazen Low Pressure [osc:nonsolidstate=Liquid ] Chromatography System using a Lobar column (Merck LiChroprep Si 60). Analytical and PHPLC were carried out on Shimadzu LC-6A, or Waters 510 instruments with UV-VIS detectors.
Standard work-up means that the organic layers orACTION extractcml:extracts were finallyACTION washedcml:washed with brine, [= ] over [= ] sodium sulfate (Na2SO4), filtered and [= ] in vacuo below [osc:temperature=30.0(oscUnits:C) ] using a rotary evaporator. All operations were carried out under nitrogen or argon. Hexane refers to n-hexane.

To asolution of {chem4} (
balancedBrackets[osc:mass=142.0(oscUnits:mg) ]
) in CH2Cl2 (
balancedBrackets[osc:volume=1.5(oscUnits:mL) ]
)ACTION was addedcml:added salt {chem9} (
balancedBrackets[osc:mass=8.17(oscUnits:mg) ]
) at [osc:temperature=298.15(oscUnits:k) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=2.0(oscUnits:h) ].ACTION Evaporationcml:evaporation of the reaction{mixture}gavea{residue}, whichACTION was purified bycml:purifiedSCC (
lbracket
Et2O-hexane, 2 : 3) toafford the cyclopentyl compound {chem7} as a [osc:colour=colorless ]. Spectral data (IR and 1H NMR) of this compound were in agreement with those of our previous report.5b
|reactionScheme|HEADER HEADER|
To asolution of the {chem11} (
balancedBrackets[osc:mass=11.9(oscUnits:g) ]
) in [= ] Py (
balancedBrackets[osc:volume=20.0(oscUnits:mL) ]
)ACTION was addedcml:addedAc2O (
balancedBrackets[osc:volume=15.0(oscUnits:mL) ]
) at [osc:temperature=298.15(oscUnits:k) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=16.0(oscUnits:h) ]. The{mixture}wasACTION pouredcml:poured into ice-water andACTION extractcml:extracted with Et2O. TheACTION extractcml:extracts wereACTION washedcml:washed successively with [= ] 5% HCl, [= ] [= ] NaHCO3 and brine.ACTION Evaporationcml:evaporation of the [= ]ACTION extractcml:extractsgavea{residue}, whichACTION was purified bycml:purifiedSCC (
balancedBracketsEt2O-hexane, 1 : 9) toafford the acetate {chem12} as a [osc:colour=colorless ]; [[alpha]]26D -42.6 (c 1.22, MeOH
); [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem12}
reactionScheme| |reactionScheme|HEADER2-[(1S,4S,6R)- and and HEADER|
Asolution of MCPBA (72%, [osc:mass=552.0(oscUnits:mg) ]
rbracket
) in [= ] CH2Cl2 (
balancedBrackets[osc:volume=5.0(oscUnits:mL) ]
)ACTION was addedcml:addedto an ice-cooledsolution of the {chem12} (
balancedBrackets[osc:mass=600.0(oscUnits:mg) ]
) in [= ] CH2Cl2 (
balancedBrackets[osc:volume=5.0(oscUnits:mL) ]
). After beingACTION stirredcml:stirred at [osc:temperature=0.0(oscUnits:C) ] for [osc:time=1.0(oscUnits:h) ], the reaction{mixture}ACTION was dilutedcml:dilutedwith Et2OandACTION washedcml:washed successively with [= ] 1% Na2S2O3, [= ] [= ] NaHCO3 and brine.ACTION Evaporationcml:evaporation of the [= ]solventgavea{residue}, whichACTION was purified bycml:purifiedSCC (
lbracket
Et2O-hexane, 1 : 5) followed by low-pressure CC (
lbracket
Et2O-benzene, 1 : 19) toafford the anti-epoxide {chem5a} and the syn- epoxide {chem5b} as [osc:colour=colorless ] oils, respectively.
|reactionScheme|HEADER HEADER|
[[alpha]]22D -10.0 (c 1.00, MeOH
rbracket
); [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem5a}
reactionScheme| |reactionScheme|HEADER HEADER|
[[alpha]]22D -30.0 (c 1.00, MeOH
rbracket
); [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem5b}
reactionScheme| {chem5a}
{chem5b}
reactionScheme|

To asolution of NaI (
balancedBrackets[osc:mass=1.35(oscUnits:g) ]
) in [= ] acetonitrile (
balancedBrackets[osc:volume=10.0(oscUnits:mL) ]
)ACTION was addedcml:addedTMSCl (
balancedBrackets[osc:volume=0.56(oscUnits:mL) ]
) at [osc:temperature=298.15(oscUnits:k) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ]for a few minutes. To this{mixture}ACTION was addedcml:addedasolution of the epoxide {chem5b} (
balancedBrackets[osc:mass=1.07(oscUnits:g) ]
) in [= ] CH2Cl2 (
balancedBrackets[osc:volume=5.0(oscUnits:mL) ]
) at [osc:temperature=298.15(oscUnits:k) ]. After beingACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=30.0(oscUnits:min) ], the reaction{mixture}ACTION was dilutedcml:dilutedwith Et2OandACTION washedcml:washed successively with [= ] 1% Na2S2O3 and brine.ACTION Evaporationcml:evaporation of the [= ]solventgavea{residue}, whichACTION was purified bycml:purifiedSCC (
balancedBracketsacetone-hexane, 1 : 4) toafford the alcohol as a [osc:colour=colorless ]. To asolution of the alcohol (
lbracket
[osc:mass=542.0(oscUnits:mg) ]
) in [= ] CH2Cl2 (
balancedBrackets[osc:volume=5.0(oscUnits:mL) ]
)ACTION was addedcml:addedEt3N (
balancedBrackets[osc:volume=0.64(oscUnits:mL) ]
), DMAP (
balancedBrackets[osc:mass=586.0(oscUnits:mg) ]
) and asolution of TBSCl (
balancedBrackets[osc:mass=433.0(oscUnits:mg) ]
) in [= ] CH2Cl2 (
balancedBrackets[osc:volume=3.0(oscUnits:mL) ]
) at [osc:temperature=298.15(oscUnits:k) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=15.0(oscUnits:h) ]. The reaction{mixture}wasACTION pouredcml:poured into ice-water andACTION extractcml:extracted with Et2O. TheACTION extractcml:extracts wereACTION washedcml:washed successively with [= ] 5% HCl, [= ] [= ] NaHCO3 and brine.ACTION Evaporationcml:evaporation of the [= ]ACTION extractcml:extractsgavea{residue}, whichACTION was purified bycml:purifiedSCC (
balancedBracketsEt2O-hexane, 1 : 9) toyield{chem12} (
lbracket
[osc:mass=611.0(oscUnits:mg) ], 75%; 60% from {chem5b}
) as a [osc:colour=colorless ]. Spectral data of this compound were identical with those of {chem12} derived from {chem11} in this paper.

To asolution of the {chem5a} (
balancedBrackets[osc:mass=178.0(oscUnits:mg) ]
) in CH2Cl2 (
balancedBrackets[osc:volume=4.0(oscUnits:mL) ]
)ACTION was addedcml:added salt {chem9} (
balancedBrackets[osc:mass=42.0(oscUnits:mg) ]
) at [osc:temperature=298.15(oscUnits:k) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=30.0(oscUnits:min) ].ACTION Evaporationcml:evaporation of the reaction{mixture}gavea{residue}, whichACTION was purified bycml:purifiedSCC (
lbracket
Et2O-hexane, 3 : 17 [~~] acetone-hexane, 1 : 5) toafford the cyclopentyl compound {chem8} and the deprotected compound {chem13} as [osc:colour=colorless ] oils, respectively.

[[alpha]]22D +10.0 (c 1.00, MeOH
rbracket
); [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.

[[alpha]]23D +5.00 (c 1.00, MeOH
rbracket
); [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.

To asolution of the {chem13} (
balancedBrackets[osc:mass=145.0(oscUnits:mg) ]
) in [= ] CH2Cl2 (
balancedBrackets[osc:volume=3.0(oscUnits:mL) ]
)ACTION was addedcml:addedEt3N (
balancedBrackets[osc:volume=0.5(oscUnits:mL) ]
), DMAP (
balancedBrackets[osc:mass=110.0(oscUnits:mg) ]
) and asolution of TBSCl (
balancedBrackets[osc:mass=106.0(oscUnits:mg) ]
) in [= ] CH2Cl2 (
balancedBrackets[osc:volume=3.0(oscUnits:mL) ]
) at [osc:temperature=298.15(oscUnits:k) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=15.0(oscUnits:h) ]. The reaction{mixture}wasACTION pouredcml:poured into ice-water, andACTION extractcml:extracted with Et2O. TheACTION extractcml:extracts wereACTION washedcml:washed successively with [= ] 5% HCl, [= ] [= ] NaHCO3 and brine.ACTION Evaporationcml:evaporation of the [= ]ACTION extractcml:extractsgavea{residue}, whichACTION was purified bycml:purifiedSCC (
lbracket
Et2O-hexane, 1 : 4) toafford {chem8} as a [osc:colour=colorless ]. Spectral properties of this compound were in agreement with those of the cyclopentyl compound {chem8} in the above rearrangement.
|reactionScheme|HEADER HEADER|
To asolution of the compound {chem8} (
balancedBrackets[osc:mass=255.0(oscUnits:mg) ]
) in MeOH (
balancedBrackets[osc:volume=5.0(oscUnits:mL) ]
)ACTION was addedcml:addedNaBH4 (
balancedBrackets[osc:mass=27.2(oscUnits:mg) ]
) at [osc:temperature=0.0(oscUnits:C) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=0.0(oscUnits:C) ] for [osc:time=30.0(oscUnits:min) ]. The reaction{mixture}wasACTION pouredcml:poured into ice-water, andACTION extractcml:extracted with Et2O. Standard work-upaffordeda{residue}, whichACTION was purified bycml:purifiedSCC (
balancedBracketsEt2O-hexane, 1 : 5) toyieldthe alcohol as a [osc:colour=colorless ]. Pri2NEt (
lbracket
[osc:volume=0.98(oscUnits:mL) ]
) and PMBMCl11 (
balancedBrackets[osc:mass=626.0(oscUnits:mg) ]
) were added to asolution of the above alcohol (
balancedBrackets[osc:mass=200.0(oscUnits:mg) ]
) in [= ] CH2Cl2 (
balancedBrackets[osc:volume=2.0(oscUnits:mL) ]
) at [osc:temperature=298.15(oscUnits:k) ]. After beingACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=16.0(oscUnits:h) ], the reaction{mixture}ACTION was dilutedcml:dilutedwith Et2Oand the organic layer wasACTION washedcml:washed successively with [= ] 5% HCl, [= ] [= ] NaHCO3 and brine.ACTION Evaporationcml:evaporation of the [= ]solution gavea{residue}, which was purified by SCC (
balancedBracketsacetone-hexane, 1 : 19) toafford the PMBM ether {chem14} (
lbracket
[osc:mass=229.0(oscUnits:mg) ], 80%; 62% from {chem8}
) as a [osc:colour=colorless ]; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem14}
reactionScheme| |reactionScheme|HEADER HEADER|
ACTION To acml:tosuspension of LAH (
balancedBrackets[osc:mass=24.0(oscUnits:mg) ]
) in [= ] Et2O (
balancedBrackets[osc:volume=5.0(oscUnits:mL) ]
)ACTION was addedcml:addeddropwise asolution of {chem14} (
balancedBrackets[osc:mass=323.0(oscUnits:mg) ]
) in [= ] Et2O (
balancedBrackets[osc:volume=15.0(oscUnits:mL) ]
) at [osc:temperature=0.0(oscUnits:C) ]. After beingACTION stirredcml:stirred at [osc:temperature=0.0(oscUnits:C) ] for [osc:time=30.0(oscUnits:min) ], the [= ] LAH was decomposed by dropwise addition of water. The{mixture} wasACTION extractcml:extracted with Et2Oand theACTION extractcml:extracts wereACTION washedcml:washed successively with [= ] 5% HCl, [= ] [= ] NaHCO3 and brine.ACTION Evaporationcml:evaporation of the [= ]solventgavea{residue}, whichACTION was purified bycml:purifiedSCC (
lbracket
acetone-hexane, 1 : 9) toafford the alcohol {chem15} as a [osc:colour=colorless ]; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem15}
reactionScheme| |reactionScheme|HEADER HEADER|
To asolution of the {chem15} (
balancedBrackets[osc:mass=125.0(oscUnits:mg) ]
) in DMSO (
balancedBrackets[osc:volume=1.0(oscUnits:mL) ]
)ACTION was addedcml:addedasolution of IBX12 (
balancedBrackets[osc:mass=188.0(oscUnits:mg) ]
) in DMSO (
balancedBrackets[osc:volume=0.67(oscUnits:mL) ]
) at [osc:temperature=298.15(oscUnits:k) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=1.0(oscUnits:h) ]. The reaction{mixture}ACTION was dilutedcml:dilutedwith water (
balancedBrackets[osc:volume=5.0(oscUnits:mL) ]
) and the [osc:colour=white ]precipitate was filtered. The filtrate wasACTION extractcml:extracted with Et2O. Standard work-upgavea{residue}, whichACTION was purified bycml:purifiedSCC (
lbracket
acetone-hexane, 1 : 9) toACTION providecml:providethe aldehyde {chem16} as a [osc:colour=colorless ]; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem16}
reactionScheme| |reactionScheme|HEADER HEADER|
To asolution of the {chem17} (
balancedBrackets[osc:mass=403.0(oscUnits:mg) ]
) in [= ] Et2O (
balancedBrackets[osc:volume=4.0(oscUnits:mL) ]
)ACTION was addedcml:addedButLi (
balancedBrackets[osc:conc=1.64(oscUnits:unknown) ] in pentane; [osc:volume=0.93(oscUnits:mL) ]
) at -[osc:temperature=78.0(oscUnits:C) ]and the{mixture}wasACTION stirredcml:stirred at -[osc:temperature=78.0(oscUnits:C) ] for [osc:time=10.0(oscUnits:min) ]. Asolution of the aldehyde {chem16} (
balancedBrackets[osc:mass=235.0(oscUnits:mg) ]
) in [= ] Et2O (
balancedBrackets[osc:volume=6.0(oscUnits:mL) ]
)ACTION was addedcml:addedto this{mixture} at -[osc:temperature=78.0(oscUnits:C) ] for [osc:time=1.0(oscUnits:h) ]. After being quenched with [= ] [= ] NH4Cl, the{mixture} wasACTION extractcml:extracted with Et2O. Standard work-upgavea{residue}, whichACTION was purified bycml:purifiedSCC (
balancedBracketsEt2O-hexane, 1 : 4) toafford the adduct as a [osc:colour=colorless ]. Then, to asolution of the adduct (
lbracket
[osc:mass=313.0(oscUnits:mg) ]
) in DMSO (
balancedBrackets[osc:volume=1.5(oscUnits:mL) ]
)ACTION was addedcml:addedasolution of IBX12 (
balancedBrackets[osc:mass=337.0(oscUnits:mg) ]
) in DMSO (
balancedBrackets[osc:volume=1.2(oscUnits:mL) ]
) at [osc:temperature=298.15(oscUnits:k) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=16.0(oscUnits:h) ]. The reaction{mixture}ACTION was dilutedcml:dilutedwith water (
balancedBrackets[osc:volume=5.0(oscUnits:mL) ]
) and the [osc:colour=white ]precipitate was filtered. The filtrate wasACTION extractcml:extracted with Et2O. Standard work-upgavea{residue}, whichACTION was purified bycml:purifiedSCC (
balancedBracketsEt2O-hexane, 3 : 17) toACTION providecml:providethe [= ] ketone {chem18} (
lbracket
[osc:mass=197.0(oscUnits:mg) ], 63%; 60% from {chem16}
) as a [osc:colour=colorless ]; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem18}
reactionScheme| |reactionScheme|HEADER HEADER|
To asolution of the {chem18} (
balancedBrackets[osc:mass=197.0(oscUnits:mg) ]
) dissolved in a{mixture} of CH2Cl2-H2O (18 : 1, [osc:volume=6.54(oscUnits:mL) ]
rbracket
)ACTION was addedcml:addedDDQ11b (
balancedBrackets[osc:mass=86.0(oscUnits:mg) ]
). After beingACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=2.0(oscUnits:h) ], the reaction{mixture} was filtered through Celite.ACTION Evaporationcml:evaporation of the filtrategavea{residue}, whichACTION was purified bycml:purifiedSCC (
lbracket
Et2O-hexane, 1 : 9) toafford the alcohol {chem19} as a [osc:colour=colorless ]; [lambda]
SPECTRUM OMITTED
; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem19}
reactionScheme|

To asolution of the {chem19} (
balancedBrackets[osc:mass=200.0(oscUnits:mg) ]
) in [= ] DMSO (
balancedBrackets[osc:volume=14.0(oscUnits:mL) ]
)ACTION was addedcml:addedAc2O (
balancedBrackets[osc:volume=7.0(oscUnits:mL) ]
) at [osc:temperature=298.15(oscUnits:k) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=16.0(oscUnits:h) ]. The reaction{mixture}wasACTION pouredcml:poured into ice-water andACTION extractcml:extracted with Et2O. TheACTION extractcml:extracts wereACTION washedcml:washed with water and [= ] [= ] NaHCO3 and brine.ACTION Evaporationcml:evaporation of the [= ]solventgavea{residue}, whichACTION was purified bycml:purifiedSCC (
lbracket
Et2O-hexane, 1 : 19) toafford the [= ] [beta]-diketone {chem20} and the acetate {chem21} as [osc:colour=colorless ] oils, respectively.
|reactionScheme|HEADER HEADER|
[[alpha]]23D -23.4 (c 0.47, CHCl3
rbracket
); [lambda]
SPECTRUM OMITTED
; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem20}
reactionScheme| |reactionScheme|HEADER HEADER|
[[alpha]]27D +10.0 (c 0.40, MeOH
rbracket
); [lambda]
SPECTRUM OMITTED
; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem21}
reactionScheme|
|reactionScheme|HEADER HEADER|
Ac2O (
balancedBrackets[osc:volume=0.5(oscUnits:mL) ]
)ACTION was addedcml:addedto asolution of the {chem20} (
balancedBrackets[osc:mass=104.0(oscUnits:mg) ]
), Et3N (
balancedBrackets[osc:volume=0.04(oscUnits:mL) ]
) and DMAP (
balancedBrackets[osc:mass=28.0(oscUnits:mg) ]
) in [= ] CH2Cl2 (
balancedBrackets[osc:volume=1.0(oscUnits:mL) ]
) at [osc:temperature=298.15(oscUnits:k) ]. After beingACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=30.0(oscUnits:min) ], the{mixture}wasACTION pouredcml:poured into ice-water andACTION extractcml:extracted with Et2O. TheACTION extractcml:extracts wereACTION washedcml:washed successively with [= ] 5% HCl, [= ] [= ] NaHCO3 and brine.ACTION Evaporationcml:evaporation of the [= ]ACTION extractcml:extractsgavea{residue}, whichACTION was purified bycml:purifiedSCC (
balancedBracketsEt2O-hexane, 1 : 4) toafford the enol acetate {chem22} as a [osc:colour=colorless ]; [[alpha]]20D -10.3 (c 0.98, CHCl3
); [lambda]
SPECTRUM OMITTED
; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem22}
reactionScheme| |reactionScheme|HEADER HEADER|
Asolution of TBAF (
balancedBrackets[osc:conc=1.0(oscUnits:unknown) ] in THF; [osc:volume=0.19(oscUnits:mL) ]
)ACTION was addedcml:addedto asolution of the {chem22} (
balancedBrackets[osc:mass=104.0(oscUnits:mg) ]
) in [= ] THF (
balancedBrackets[osc:volume=4.0(oscUnits:mL) ]
) at [osc:temperature=0.0(oscUnits:C) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=0.0(oscUnits:C) ] for [osc:time=1.0(oscUnits:h) ]. The reaction{mixture}ACTION was dilutedcml:dilutedwith Et2O. Standard work-upgavea{residue}, whichACTION was purified bycml:purifiedSCC (
balancedBracketsEt2O-hexane, 1 : 4 [~~] acetone-hexane, 1 : 4) toafford the alcohol {chem23} as a [osc:colour=colorless ]; [[alpha]]24D +0.98 (c 1.02, CHCl3
); [lambda]
SPECTRUM OMITTED
; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem23}
reactionScheme| |reactionScheme|HEADER HEADER|
To asolution of the {chem23} (
balancedBrackets[osc:mass=54.0(oscUnits:mg) ]
) in DMSO (
balancedBrackets[osc:volume=0.25(oscUnits:mL) ]
)ACTION was addedcml:addedasolution of IBX12 (
balancedBrackets[osc:mass=72.0(oscUnits:mg) ]
) in DMSO (
balancedBrackets[osc:volume=0.26(oscUnits:mL) ]
) at [osc:temperature=298.15(oscUnits:k) ]and the{mixture}wasACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=1.0(oscUnits:h) ]. The reaction{mixture}ACTION was dilutedcml:dilutedwith water (
balancedBrackets[osc:volume=3.0(oscUnits:mL) ]
) and the [osc:colour=white ]precipitate was filtered. The filtrate wasACTION extractcml:extracted with Et2O. Standard work-upgavea{residue}, whichACTION was purified bycml:purifiedSCC (
balancedBracketsacetone-hexane, 3 : 17) toafford the aldehyde as a [osc:colour=pale ]. A{mixture} of 47% [= ] HF-CH3CN (1 : 19; [osc:volume=0.4(oscUnits:mL) ]
)ACTION was addedcml:addedto asolution of this aldehyde (
balancedBrackets[osc:mass=33.0(oscUnits:mg) ]
) in a{mixture} of CH3CN-THF (9 : 1; [osc:volume=4.0(oscUnits:mL) ]
rbracket
) at [osc:temperature=298.15(oscUnits:k) ]. After beingACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=1.5(oscUnits:h) ], the reaction{mixture} was quenched with [= ] [= ] NaHCO3andACTION extractcml:extracted with Et2O. Standard work-upgavea{residue}, whichACTION was purified bycml:purifiedSCC (
balancedBracketsacetone-hexane, 3 : 7) toACTION providecml:providethe desilylated aldehyde {chem10b} (
lbracket
[osc:mass=22.0(oscUnits:mg) ], 92%; 55% from {chem23}
) as a [osc:colour=pale ]; [[alpha]]26D -10.0 (c 0.40, CHCl3
rbracket
); [lambda]
SPECTRUM OMITTED
; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem10b}
reactionScheme| |reactionScheme|HEADER HEADER|
An [= ]solution (
balancedBrackets[osc:volume=0.1(oscUnits:mL) ]
) prepared from PTSA (
balancedBrackets[osc:mass=500.0(oscUnits:mg) ]
) and H3PO4 (
balancedBrackets[osc:mass=725.0(oscUnits:mg) ]
) in MeOH (
balancedBrackets[osc:volume=37.5(oscUnits:mL) ]
) and (
balancedBrackets[osc:volume=0.1(oscUnits:mL) ]
) were added to asolution of the Wittig salt {chem24} (
balancedBrackets[osc:mass=35.6(oscUnits:mg) ]
) in MeOH (
balancedBrackets[osc:volume=1.0(oscUnits:mL) ]
). The{mixture}wasACTION stirredcml:stirred at [osc:temperature=298.15(oscUnits:k) ] for [osc:time=1.0(oscUnits:h) ] and neutralized with NaOMe (
balancedBrackets[osc:conc=1.0(oscUnits:unknown) ] in MeOH
) until just before the [osc:colour=red ] color of an appeared.ACTION Evaporationcml:evaporationof the solventACTION providedcml:provide the Wittig salt {chem25}, to which asolution of the aldehyde {chem10b} (
balancedBrackets[osc:mass=9.8(oscUnits:mg) ]
) in propan-2-ol (
balancedBrackets[osc:volume=1.5(oscUnits:mL) ]
) was added. To the{mixture}, a [= ]solution (
balancedBrackets[osc:volume=1.0(oscUnits:mL) ]
) of KOH (
balancedBrackets[osc:mass=500.0(oscUnits:mg) ]
) dissolved in water (
balancedBrackets[osc:volume=1.0(oscUnits:mL) ]
) and propan-2-ol (
balancedBrackets[osc:volume=10.0(oscUnits:mL) ]
)ACTION was addedcml:addeddropwise at [osc:temperature=0.0(oscUnits:C) ]. After beingACTION stirredcml:stirred at [osc:temperature=0.0(oscUnits:C) ] for [osc:time=1.0(oscUnits:h) ], the{mixture}wasACTION pouredcml:poured into ice-water, andACTION extractcml:extracted with Et2O. TheACTION extractcml:extracts were shaken with [= ] 5% HCl until the fine structure disappeared on UV-VIS,ACTION washedcml:washed successively with [= ] [= ] NaHCO3 and brine.ACTION Evaporationcml:evaporation of the [= ]ACTION extractcml:extractsACTION providedcml:providea{residue}, whichACTION was purified bycml:purifiedSCC (
lbracket
acetone-hexane, 1 : 4) toafford an isomeric{mixture} of apocarotenal {chem26} in which the main product was all-Eisomer. Purification of a part of the isomeric{mixture} by PTLC (
lbracket
acetone-hexane, 3 : 7)ACTION providedcml:provide the all-E isomer as an [osc:colour=orange ]; [lambda]
SPECTRUM OMITTED
; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.
{chem26}
reactionScheme|

A [= ]solution (
balancedBrackets[osc:volume=3.0(oscUnits:mL) ]
) of KOH (
balancedBrackets[osc:mass=500.0(oscUnits:mg) ]
) dissolved in water (
balancedBrackets[osc:volume=1.0(oscUnits:mL) ]
) and propan-2-ol (
balancedBrackets[osc:volume=10.0(oscUnits:mL) ]
)ACTION was addedcml:addeddropwise to asolution of the apocarotenal {chem26} (
balancedBrackets[osc:mass=11.7(oscUnits:mg) ]
) and the Wittig salt {chem27} (
balancedBrackets[osc:mass=61.0(oscUnits:mg) ]
) in propan-2-ol (
balancedBrackets[osc:volume=6.0(oscUnits:mL) ]
) at [osc:temperature=0.0(oscUnits:C) ]. After beingACTION stirredcml:stirred at [osc:temperature=0.0(oscUnits:C) ] for [osc:time=30.0(oscUnits:min) ], the reaction{mixture} wasACTION extractcml:extracted with Et2OandACTION washedcml:washed with [= ] [= ] NH4Cl and brine.ACTION Evaporationcml:evaporation of the [= ]ACTION extractcml:extractsgavea{residue}, whichACTION was purified bycml:purifiedSCC (
lbracket
acetone-hexane, 3 : 7) toafford an isomeric{mixture} of mytiloxanthin . Purification of a part of the isomeric{mixture} by PHPLC [CHEMCOSORB 7ODS-H 1.0 × 30 cm; H2O-MeOH, 4 : 96; [osc:conc=460.0(oscUnits:unknown) ]detect.]ACTION providedcml:provide the all-E isomer {chem1}, 9Z one {chem28} and 9Z,11Z one {chem29} as [osc:colour=red ] solids respectively, in a [= ] state. Spectral properties of the synthetic all-E isomer {chem1} and 9Z one {chem28} were in agreement with those of a natural specimen.

CD ()/nm ([Delta][epsilon]) 230 (-0.5), 275 (0), 294 (+0.7), 310 (0), 360 (-0.3); [lambda]
SPECTRUM OMITTED
, [lambda]
SPECTRUM OMITTED
; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
.

CD ()/nm ([Delta][epsilon]) 230 (-0.8), 247 (0), 258 (+1.0), 280 (0), 300 (-0.3), 310 (0), 350 (+1.0), 370 (0); [lambda]
SPECTRUM OMITTED
[lambda]
SPECTRUM OMITTED
; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
(the cross peak was observed between 11-H and 5-Me in the NOESY spectrum) .

[lambda]
SPECTRUM OMITTED
, [lambda]
SPECTRUM OMITTED
; [nu]
SPECTRUM OMITTED
; [delta]
SPECTRUM OMITTED
(the cross peak was observed between 11-H and 12-H in the NOESY spectrum) .

##

##

##

##

##

##

##

##

##

##

##

##

##

##

##

##

##

##

##

##

##

##