The synthesis of ventiloquinone F and isoventiloquinone F as racemates

Article abstract of DOI:10.1002/ejoc.200400489

Racemic ventiloquinone F and isoventiloquinone F have been synthesized utilizing an initial Stobbe condensation, followed by mercury (II)-mediated ring closure and catalytic hydrogenolysis as key steps in the synthetic protocol. Wiley-VCH Verlag GmbH & Co

Full text of DOI:10.1002/ejoc.200400489

FULL PAPER
The Synthesis of Ventiloquinone F and Isoventiloquinone F as Racemates
Robin G. F. Giles,[a] Ivan R. Green,*[b] and Nestor van Eeden[b]
Keywords: Natural products / Quinones / Cyclization / Oxidation / Hydrogenolysis
Racemic ventiloquinone F and isoventiloquinone F have
been synthesized utilizing an initial Stobbe condensation,
followed by mercury(II)-mediated ring closure and catalytic
hydrogenolysis as key steps in the synthetic protocol.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
Interest in the family of ventiloquinones may be attri-
buted to the pioneering work by Thomson et al.[1] who de-
scribed the isolation and structural elucidation of primarily
isofuranonapthoquinones found in the extracts of the root
bark of the Indian plants ventilago madderaspatana and V.
calyculata. Following on this seminal work Thomson et
al.[2] extended their investigations and described eleven new
ventiloquinones isolated from the same plants but in this
case their work concerned mainly (1R,3S)-1,3-dimeth-
ylnaphtho[2,3-c]pyran-5,10- and 6,9-quinones. Additionally
ventiloquinones L, M, N and O were isolated form V.
goughii[3] while ventiloquinones G, L, and M were reported
to be found in the root bark of Fijian V. vitiensis.[4] While
the Thomson group was able to assign structures to most
of the ventiloquinones based on spectral analyses, a few
ambiguities still remain viz., ventiloquinones A and J.[2]
A
more comprehensive review on the isolation and structural
elucidation of naturally occurring pyranonaphthoquinones
has also appeared recently.[5]
Brimble et al.[6] recently published a fairly comprehensive
review on the synthesis of pyranonaphthoquinone anti-
biotics. However and more specifically, Brassard et al.[7] de-
scribed some early protocols developed for the synthesis of
ventilagone
1
and ventiloquinone
H
2
employing
Figure 1. Examples of naphthophyranquinones
DielsϪAlder chemistry. This was followed by the work of
Giles et al.[8] who described their work on the syntheses
of ventiloquinones E (3), G (4) and the regioisomer 5 of
ventiloquinone J (6) (Figure 1). We have recently developed
unambiguous syntheses for ventiloquinone J and isoventil-
oquinone J as their racemates, thus confirming the structure
of ventiloquinone J to be 6.[9] Different synthetic ap-
proaches were additionally described for the synthesis of
ventiloquinone E (3) and ventilagone (1) by Cameron et
al.[10,11] Further modified approaches towards the syntheses
of ventiloquinones C, D, E (3) and G (4) were described by
Brassard et al.[12]
Since our group has a strong interest in naphtho[2,3-c]py-
ran-6,9-quinones and their evaluation as antibiotic and
antifungal agents, we needed as part of our programme to
synthesize both ventiloquinone F (7) and its C3 epimer iso-
[a]
Department of Chemistry, Murdoch University,
Murdoch, WA 6150, Australia
[b]
Department of Chemistry, University of the Western Cape,
P/Bag X17, Bellville, 7530, South Africa
Fax: (internat.) ϩ 27-21-9593055
E-mail: igreen@uwc.ac.za
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400489
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Synthesis of Ventiloquinone F and Isoventiloquinone F
FULL PAPER
ventiloquinone F (8) for comparative evaluations. This
paper describes their syntheses.
The naphthalene oxygenation pattern of ventiloquinone
F (7) directed our approach to Stobbe methodology and
despite some elegant work by Sargent et al.[13] on the use
of phosphoranes[14] and McCombie et al.[15] on the use of
triphenylphosphane[15] as alternative methods, our experi-
ence[16] and some others[17,18] in this most classic of reac-
tions, favoured the former approach.
Thus the trimethoxybenzaldehyde 9[19] was reacted under
typical Stobbe conditions with dimethyl succinate to afford,
after cyclisation, the desired methyl naphthoate 10 in an
overall yield of 84% for the two steps. Chemoselective hy-
drolysis of the naphthyl acetate ester 10 with 1% (w/v) meth-
anolic potassium hydroxide produced the expected naph-
thol 11 (94%) with the H-bonded 4-OH appearing as a D2O
1
exchangeable signal at δ ϭ 9.70 ppm in the H NMR spec-
trum. Allylation of the latter phenolic group to afford 12
was effected in 92% yield by treatment with allyl bromide
and potassium carbonate in boiling acetone under vigorous
stirring[20] (Scheme 1).
Naphthaldehyde 16 was pivotal to the synthetic scheme
envisaged and since at least two routes to it were feasible
using the same reaction conditions but in a different se-
quence, the more efficient route had to be discovered.
Consequently pyrolysis of naphthyl ether 12 at 180 °C un-
der nitrogen afforded phenol 13 in 98% as demonstrated by
the fact that only two one-proton singlets were evident in
1
the H NMR spectrum, viz., at δ ϭ 6.58 and 8.24 ppm for
7-H and 1-H respectively. Benzylation of the phenol 13
using benzyl bromide and potassium carbonate in boiling
acetone with vigorous stirring afforded the desired benzyl
ether 14 in 97% yield. We found that the most convenient
route for the large scale transformation of the naphthyl es-
ter 14 into the corresponding aldehyde 16 was to first re-
duce the former compound to the naphthyl alcohol 15 with
lithium aluminium hydride (LAH) in THF at 50 °C in es-
sentially quantitative yield followed by oxidation, em-
ploying activated manganese dioxide in boiling benzene,[21]
to produce the desired aldehyde 16 in 69% yield.
Scheme 1. Reagents and conditions: (i) dimethyl malonate/KOtBu/
tert-butyl alcohol reflux then NaOAc/Ac2O reflux; (ii) 1% KOH/
MeOH; (iii) allyl bromide/K2CO3/acetone/reflux; (iv) 180 °C/N2;
(v) BnBr/K2CO3/acetone/reflux; (vi) LAH/THF; (vii) MnO2/ben-
zene/reflux
In the alternative synthetic sequence followed, methyl
naphthoate 12 was reduced (LAH/THF) to the correspond- acetonitrile afforded two major fractions viz., a faster mov-
ing naphthyl alcohol 17 (100%) followed by oxidation ing yellow Fraction A (46%) and a slower moving reddish
(MnO2/benzene) to afford aldehyde 18 (57%) which was Fraction B (42%). Both fractions were separately resub-
subsequently pyrolysed to phenol 19 (100%), benzylation of jected to careful chromatographic separation. In this way
which (BnBr/K2CO3) produced the same aldehyde 16 Fraction A yielded the two individual naphthopyran-6,9-
(57%). The overall yield for the conversion sequence 12 Ǟ quinones 23 (22%) and 25 (24%). Assignment of structure
17 Ǟ 18 Ǟ 19 Ǟ 16 was 32% while that of 12 Ǟ 13 Ǟ 14 23 to the first naphthopyran-6,9-quinone to elute is based
Ǟ 15 Ǟ 16 was 66% and thus the latter sequence was fav- inter alia on the following one-proton signals for the pyran
oured.
ring in the 1H NMR spectrum; a ddd at δ ϭ 2.42 ppm with
With quantities of aldehyde 16 in hand, treatment with J ϭ 17.6 Hz for geminal coupling between the dia-
freshly prepared methylmagnesium iodide afforded alcohol stereotopic 4Ј-H’s, J ϭ 11.0 Hz for coupling between 4-Hax
20 in quantitative yield. This was followed by intramolecu- and 3-Hax, and J ϭ 1.8 Hz representing coupling between
lar acetoxymercuration[22] followed by demercuration using 4-Hax and 1-Hax and is assigned to pseudoaxial 4-H; a ddd
sodium borohydride[23] which afforded an inseparable mix- at δ ϭ 2.90 ppm with a similar J ϭ 17.6 Hz representing
ture of the naphthopyrans 21 and 22 in an overall yield of coupling between 4-Heq and 4-Hax, J ϭ 3.0 Hz for coupling
71% and in a 1:1 ratio (Scheme 2). Oxidation of this latter between 4-Heq and 3-Hax, J ϭ 1.0 Hz representing coupling
mixture with cerium() ammonium nitrate in aqueous between 4-Heq and 1-Hax and is assigned to pseudoequa-
Eur. J. Org. Chem. 2004, 4416Ϫ4423
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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R. G. F. Giles, I. R. Green, N. van Eeden
FULL PAPER
Scheme 2. Reagents and conditions: (i) MeMgBr/diethyl ether; (ii) Hg(OAc)2/THF/H2O/NaOH/NaBH4; (iii) cerium() ammonium ni-
trate/H2O/CH3CN
1
torial 4-H; a multiplet at δ ϭ 3.68 ppm assigned to 3-Hax; the comparative one-proton signals of its H NMR spec-
a ddq at δ ϭ 4.85 ppm with J ϭ 6.6 Hz representing coup- trum to quinone 23. The second of the 6,7-quinones to elute
ling of 1-Hax to the C1ϪCH3, J ϭ 1.8 Hz representing was assigned the structure 26 based on arguments dis-
coupling between 1-Hax and 4-Hax, J ϭ 1.0 Hz representing cussed earlier.
coupling between 1-Hax and 4-Heq and is assigned to the
The UV spectra of 6,9-quinones 23 and 25 displayed
pseudoaxial 1-H.[8,24] The second naphthopyran-6,9-quin- λmax. values at 251, 286 and 359 nm compared to those of
one to elute was assigned the structure 25 based on obvious the 6,7-quinones 24 and 26 which displayed λmax. values of
1
similarities in the H NMR spectrum to quinone 23 with a 251, 288 and 372 nm. Differences in the IR spectra were
major difference being in the position of the signal due to also noted in that the 6,9-quinones 23 and 25 had ν bands
3-Haxwhich appeared as a multiplet at δ ϭ 3.95 ppm that at 1648 and 1690 cmϪ1 compared to the 6,7-diones 24 and
allowed assignment of a trans-1,3-dimethyl structure.[8,24]
26 that had ν bands at 1660 and 1709 cmϪ1 as expected.[26]
Fraction B afforded the two individual naphthopyran- The alternative oxidative demethylation protocol of Rapo-
6,7-quinones 24 (18%) and 26 (24%). Assignment of the cis port[27] when applied to the mixture of naphthopyrans 21
structure 24 to the first 6,7-quinone to elute was based on and 22 in the hope of reducing the undesired formation of
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Eur. J. Org. Chem. 2004, 4416Ϫ4423

Synthesis of Ventiloquinone F and Isoventiloquinone F
FULL PAPER
1
6,7-diones 24 and 26 failed to effect this, with all four qui- molecule (213 °C)[2] and the H NMR spectrum was ident-
1
nones being produced, but in much lower yields.
ical to that published.[2] As anticipated, the H NMR spec-
For convenience, the mixture of naphthopyran-6,9-qui- tra for quinones 7 and 8 were similar and the signals for
nones 23 and 25 was subjected to catalytic hydrogenolysis. the proton 3-Hax proved to be diagnostic viz., for quinone
Chromatographic purification of the crude product gave the 7 it appeared as a ddq at δ ϭ 3.75 ppm while for quinone
expected mixture of quinones 7 and 8 (43%) followed by a 8 it appeared as an multiplet at δ ϭ 4.05 ppm.[8,25]
third major fraction 28 (40%), arising from the additional
Catalytic hydrogenolysis of the 6,7-quinone 26 only oc-
hydrogenolysis of the C1/O2 benzylic bond The assignment curred when a trace amount of concentrated aqueous hy-
was supported by a high resolution mass spectrum. The drogen chloride was added to the mixture in ethyl acetate.
hydroxy group was confirmed by a broad band at 3402 Again after two mol equivalents of H2 had been absorbed,
cmϪ1 in the IR spectrum while a strong band at 1661 cmϪ1 the reaction was stopped to initially afford an unstable
confirmed the 1,4-dione configuration.[26] The typical sig- amorphous yellow clay from which a yellow crystalline mol-
1
nals in the H NMR spectrum for the pyran ring protons ecule was isolated with difficulty and to which structure 29
were replaced by the following: A three-proton triplet at (Figure 2) has been assigned based inter alia on a high
δ ϭ 1.25 ppm (J ϭ 7.8 Hz) and a two-proton doublet of resolution mass spectrum. A strong broad peak at 3550
quadruplets at δ ϭ 2.80 ppm (J ϭ 7.6, 7.8 Hz) which is cmϪ1 in addition to a strong absorption at 1667 cmϪ1 in
assigned to the CH3CH2 side chain at C6. A three-proton the IR spectrum supported the presence of the hydroxy and
doublet at δ ϭ 1.32 ppm (J ϭ 6.2 Hz) was coupled to a quinonoid systems while λmax. values of 258, 281 and
one-proton multiplet at δ ϭ 4.15 ppm which in turn was 355 nm in the UV spectrum indicated the 6,9- rather than
coupled to a two-proton doublet at δ ϭ 2.93 ppm (J ϭ 6.6 the 6,7-quinone isomer.[26] The absence of the methoxy sig-
Hz) and is assigned to the CH3CH(OH)CH2 side chain at nal together with the retention of the benzyl group signals
1
C7. Two dimensional COSY spectroscopy confirmed each in the H NMR spectrum further supported the assigned
of the connectivities in the ethyl and 2-hydroxypropyl side structure.
chains. In addition, two one-proton D2O exchangeable sig-
nals appeared at δ ϭ 1.90 ppm for the C2ЈϪOH of the 2Ј-
hydroxypropyl side chain at C7 and the other at δ ϭ
12.32 ppm for the strongly H-bonded 8-OH group. A pos-
sible mechanism for the over reduction is illustrated in
Scheme 3 demonstrating the influence of the electron-do-
nating ability of the C7ϪOCH3 group after the initial
hydrogenation to form quinol 27.
Figure 2. Hydrogenolysis product of 26
Thus an efficient protocol has been developed for the
synthesis of rac-ventiloquinone F (7) and its diastereoiso-
mer, rac-isoventiloquinone F (8).
Experimental Section
1
General Remarks: H and 13C NMR spectra were recorded with a
Varian 200 MHz spectrometer at 20 °C in CDCl3 and J values are
given in Hz (CHCl3 at δ ϭ 7.26 ppm and CDCl3 at δ ϭ 77.1 ppm
as internal standards respectively). Infrared spectra were measured
as KBr discs with a PerkinϪElmer FT-IR 1000 PC spectrometer.
Ultraviolet spectra were recorded in ethyl alcohol with a GBC 920
spectrometer. Mass spectra were recorded with a VG 70E MS spec-
trometer. Melting points are uncorrected and were measured with
a FischerϪJohn melting point apparatus. Elemental analysis was
performed with a Carlo Erba 1500 NA analyzer. Preparative col-
umn chromatography was carried out on dry-packed columns using
Silica Gel 60 (particle size 0.063Ϫ0.02 nm). The term ‘‘residue ob-
tained upon workup’’ refers to the drying of the extract over mag-
nesium sulfate, filtration and evaporation of solvent. Hexane refers
to that fraction of b.p. 65Ϫ70 °C.
Scheme 3. Suggested mechanism for the formation of alcohol 28
derived from pyrans 23/25
However, by stopping the reduction of the mixture of 21
and 22 after 2 mol equivalents of H2 were absorbed, ventil-
oquinone F (7) and isoventiloquinone F (8) were produced
in yields of 44% and 46% respectively following chromatog-
raphy. As expected, the m.p. for the rac-ventiloquinone F
Methyl 4-Acetoxy-5,6,8-trimethoxy-2-naphthoate (10): The 2,4,5-
trimethoxybenzaldehyde (9)[19] (8.0 g, 40.8 mmol) and dimethyl
succinate (8.0 g, 54.8 mmol) were dissolved in hot (55 °C) dry tert-
butyl alcohol (80 mL). This hot solution was added dropwise over
(7) (197Ϫ199 °C) was lower than that of the chirally pure 20 min to a rapidly stirred solution of KOtBu [from potassium (2 g,
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R. G. F. Giles, I. R. Green, N. van Eeden
FULL PAPER
53.1 mmol) in tert-butyl alcohol (50 mL)], under reflux and nitro-
gen. Stirring and heating were continued for 2 h after which the
cooled solution was poured into water (600 mL), acidified (litmus)
with 5  HCl and extracted with diethyl ether. The ethereal solu-
tion was extracted with saturated aqueous sodium hydrogen car-
bonate and the combined alkaline extracts were then acidified (lit-
mus) with 5  HCl and then extracted with diethyl ether. The resi-
due obtained upon workup (12.1 g, 96% of the itaconic acid) was
heated with stirring under reflux in acetic anhydride (100 mL) con-
taining sodium acetate (4.8 g, 58.8 mmol) under nitrogen for 6 h.
The cooled mixture was then poured onto ice/water (800 mL) and
vigorously stirred to produce the naphthoate 10 (11.4 g, 84%) as
yellow crystals, m.p. 130Ϫ132 °C (from ethanol). IR: ν˜ ϭ 1690 and
137.4, 149.3, 151.1, 153.9, 168.5 ppm. C18H20O6 (332.4): calcd. C
65.06, H 6.02; found C 65.19, H 6.10.
Methyl 4-Benzyloxy-5,6,8-trimethoxy-3-(prop-2Ј-enyl)-2-naphthoate
(14): A solution of naphthoate 13 (2.29 g, 6.90 mmol) in acetone
(110 mL) containing potassium carbonate (2.77 g, 20.04 mmol) was
treated with benzyl bromide (3.43 g, 20.05 mmol) and the resulting
mixture was vigorously stirred under reflux under N2 for 24 h. The
cooled mixture was filtered and the residue obtained upon workup
was chromatographed with EtOAc/hexane (2:3) as eluent to yield
the naphthoate 14 (2.89 g, 97%) as off-white crystals, m.p. 94Ϫ95
°C (from hexane/EtOAc). IR: ν˜ ϭ 1705 cmϪ1 (CϭO). 1H NMR:
δ ϭ 3.72 (s, 3 H, CO2CH3), 3.91, 4.03 (each s, each 3 H, OCH3),
4.04 (sharp m, 5 H, OCH3 and 1Ј-H), 4.88 (dt, 3J ϭ 10.8, 4J ϭ 1.8
1
1705 cmϪ1 (s, CϭO). H NMR: δ ϭ 2.38 (s, 3 H, OCOCH3), 3.82
3
4
Hz, 1 H, cis 3Ј-H), 4.94 (s, 2 H, CH2Ph), 5.00 (dt, J ϭ 17.0, J ϭ
1.8 Hz, 1 H, trans 3Ј-H), 6.08 (m, 1 H, 2Ј-H), 6.71 (s, 1 H, 7-H),
7.44 (m, 5 H, Ph), 8.61 (s, 1 H, 1-H) ppm. 13C NMR: δ ϭ 30.5,
52.1, 56.0, 57.0, 62.5, 77.0, 94.9, 114.9, 120.9, 122.5, 125.8, 126.6,
127.8, 128.3 (ϫ 2), 128.4 (ϫ 2), 131.0, 136.1, 138.1, 138.2, 151.9,
152.2, 153.8, 168.4 ppm. C25H26O6 (422.5): calcd. C 71.09, H 6.16;
found C 71.47, H 6.05.
(s, 3 H, CO2CH3), 3.95, 4.00 and 4.02 (each s, each 3 H, OCH3),
3
3
6.70 (s, 1 H, 7-H), 7.67 (d, J ϭ 1.8 Hz, 1 H, 3-H), 8.85 (d, J ϭ
1.8 Hz, 1 H, 1-H) ppm. 13C NMR: δ ϭ 20.8, 52.3, 56.1, 56.9, 62.0,
95.8, 120.4, 122.1, 124.1, 124.5, 124.9, 135.6, 145.2, 152.5, 154.3,
166.6, 169.9 ppm. C17H18O7 (334.3): calcd. C 61.08, H 5.39; found
C 61.26, H 5.45.
Methyl 4-Hydroxy-5,6,8-trimethoxy-2-naphthoate (11): A solution
of the naphthyl ester 10 (5 g, 15.02 mmol) in methanolic potassium
hydroxide (150 mL of a 1% w/v solution) was stirred under gentle
reflux for 15 min. The cooled mixture was poured into water
(600 mL) and acidified (litmus) with 5  HCl solution followed by
extraction with dichloromethane. The residue obtained upon
workup afforded the naphthol 11 (4.14 g, 94%) as white crystals,
m.p. 156Ϫ157 °C (from ethanol). IR: ν˜ ϭ 3280 (O-H), 1705 cmϪ1
4-Benzyloxy-2-hydroxymethyl-5,6,8-trimethoxy-3-(prop-2Ј-enyl)-
naphthalene (15): To a slurry of lithium aluminium hydride (LAH)
(140 mg, 3.55 mmol) in THF (10 mL) under N2 at 25 °C was added
a solution of the naphthoate 14 (1.0 g, 2.4 mmol) in THF (15 mL)
dropwise. The reaction mixture was then heated to 50 °C and main-
tained at this temperature for 30 min after which the cooled mix-
ture was carefully treated with saturated ammonium chloride (15
drops) followed by water (30 mL) and finally extracted with di-
chloromethane. The residue obtained upon workup was chromato-
graphed with EtOAc/hexane (2:3) as eluent to afford the alcohol
15 (930 mg, 100%) as a thick colourless oil IR (film: ν˜ ϭ 3450 cmϪ1
1
(CϭO). H NMR: δ ϭ 3.94 (s, 3 H, CO2CH3), 4.02 (s, 9 H, 3 ϫ
3
OCH3), 6.64 (s, 1 H, 7-H), 7.43 (d, J ϭ 1.4 Hz, 1 H, 3-H), 8.42
(d, 3J ϭ 1.4, 1-H), 9.70 (s, 1 H, D2O exchangeable, 4-OH) ppm.
13C NMR: δ ϭ 52.2, 56.0, 57.1, 62.3, 95.5, 97.6, 110.5, 116.7, 120.7,
122.0, 126.4, 149.5, 153.4, 154.4, 167.3 ppm. C15H16O6 (292.3):
calcd. C 61.64, H 5.47; found C 61.34, H 5.86.
1
3
(OH). H NMR: δ ϭ 3.37 (s, 3 H, OCH3), 3.77 (dt, J ϭ 5.2, 4J ϭ
1.8 Hz, 2 H, 1Ј-H), 4.01, 4.03 (each s, each 3 H, OCH3), 4.81 (s, 2
3
4
H, C3ϪCH2OH), 4.87 (dt, J ϭ 18.0, J ϭ 1.8 Hz, 1 H, trans 3Ј-
3
4
Methyl 5,6,8-Trimethoxy-4-(prop-2Ј-enyloxy)-2-naphthoate (12): To
a solution of the naphthol 11 (4.14 g, 14.20 mmol) in acetone
(150 mL) containing potassium carbonate (9.9 g, 71.1 mmol) was
added allyl bromide (8.6 g, 71.1 mmol) and the resulting mixture
was vigorously stirred and heated under reflux under nitrogen for
12 h. The cooled mixture was filtered and the solvents evaporated
to afford the naphthoate 12 (4.6 g, 92%) as light brown needles,
m.p. 130Ϫ132 °C (from hexane/EtOAc). IR: ν˜ ϭ 1715 cmϪ1 (Cϭ
O). 1H NMR: δ ϭ 3.82 (s, 3 H, CO2CH3), 3.95 (s, 3 H, OCH3),
H), 4.96 (s, 2 H, CH2Ph), 5.05 (dt, J ϭ 11.0, J ϭ 1.8 Hz, 1 H,
cis 3Ј-H), 6.13 (m, 1 H, 2Ј-H), 6.70 (s, 1 H, 7-H), 7.42 (m, 6 H, 1-
D2O exchangeable proton, Ph and C2ϪCH2OH), 8.07 (s, 1 H, 1-
H) ppm. 13C NMR: δ ϭ 25.7, 30.2, 56.0, 57.2, 62.4, 77.0, 95.1,
115.4, 118.0, 123.6, 127.1, 127.7, 128.3, 128.4 (ϫ 2), 128.6, 129.8,
135.9, 138.1, 138.2, 150.2, 151.8, 152.8 ppm. C24H26O5 (394.5):
calcd. C 73.10, H 6.60; found 73.40, H 6.90.
4-Benzyloxy-5,6,8-trimethoxy-3-(prop-2Ј-enyl)naphthalene-2-carb-
aldehyde (16): To a solution of alcohol 15 (2.57 g, 6.52 mmol) in
benzene (100 mL) was added activated manganese dioxide (15 g)
and the mixture was stirred under reflux under N2 for 18 h. The
cooled mixture was filtered and the residue obtained after removal
of solvent was chromatographed with EtOAc/hexane (3:7) as eluent
to give the aldehyde 16 (1.76 g, 69%) as yellow crystals, m.p.
109Ϫ110 °C (from EtOAc/hexane): ν˜ ϭ 1681 cmϪ1 (CϭO). 1H
NMR: δ ϭ 3.72 (s, 3 H, OCH3), 4.06 (s, 6 H, 2 ϫ OCH3), 4.09 (dt,
3J ϭ 6.0, 4J ϭ 1.8 Hz, 2 H, 1Ј-H), 4.91 (dt, 3J ϭ 17.6, 4J ϭ 1.8
Hz, 1 H, trans 3Ј-H), 4.96 (s, 2 H, CH2Ph), 5.03 (dt, 3J ϭ 10.2,
4J ϭ 1.8 Hz, 1 H, cis 3Ј-H), 6.14 (m, 1 H, 2Ј-H), 6.73 (s, 1 H, 7-
H), 7.43 (m, 5 H, Ph), 8.60 (s, 1 H, 1-H), 10.18 (s, 1 H, C2ϪCHO)
ppm. 13C NMR: δ ϭ 29.2, 56.1, 56.9, 62.5, 77.1, 94.8, 115.5, 121.0,
126.7, 127.1 (ϫ 2), 128.3 (ϫ 2), 128.4 (ϫ 2), 130.5, 130.6, 136.3,
138.0 (ϫ 2), 151.9, 153.8, 154.6, 192.3 ppm. C24H24O5 (392.4):
calcd. C 73.47, H 6.12; found C 73.78, H 6.41.
3
4
4.01 (s, 6 H, 2 ϫ OCH3), 4.71 (dt, J ϭ 5.0, J ϭ 1.2 Hz, 2 H, 1Ј-
3
4
3
H), 5.33 (dt, J ϭ 10.6, J ϭ 1.4 Hz, 1 H, cis 3Ј-H), 5.60 (dt, J ϭ
17.2, J ϭ 1.4 Hz, 1 H, trans 3Ј-H), 6.21 (m, 1 H, 2Ј-H), 6.72 (s, 1
4
H, 7-H), 7.41 (d, 3J ϭ 1.4 Hz, 1 H, 3-H), and 8.57 (d, 3J ϭ 1.4 Hz,
1 H, 1-H) ppm. 13C NMR: δ ϭ 52.2, 56.0, 57.4, 62.1, 70.5, 96.3,
107.8, 117.7, 118.8, 120.6, 122.4, 124.8, 133.3, 137.9, 152.4, 153.6,
154.7, 167.5 ppm. C18H20O6 (332.4): calcd. C 65.06, H 6.02; found
C 65.25, H 6.38.
Methyl 4-Hydroxy-5,6,8-trimethoxy-3-(prop-2Ј-enyl)-2-naphthoate
(13): Pyrolysis of the naphthoate 12 (2.34 g, 7.04 mmol) at 180 °C
under N2 for 2 h afforded the naphthoate 13 (2.29 g; 98%) as light
brown crystals, m.p. 94Ϫ96 °C (from hexane/EtOAc). IR: ν˜ ϭ 3270
1
3
4
(OH), 1705 cmϪ1 (CϭO). H NMR: δ ϭ 3.87 (dt, J ϭ 5.8, J ϭ
1.5 Hz, 2 H, 1Ј-H), 3.90 (s, 3 H, CO2CH3), 3.98 (s, 3 H, OCH3),
4.00 (s, 6 H, 2 ϫ OCH3), 4.97 (dt, 3J ϭ 11.1, 4J ϭ 1.5 Hz, 1 H, cis
3
4
3Ј-H), 5.04 (dt, J ϭ 18.0, J ϭ 1.5 Hz, 1 H, trans 3Ј-H), 6.11 (m,
1 H, 2Ј-H), 6.58 (s, 1 H, 7-H), 8.24 (s, 1 H, 1-H), 10.08 (s, 1 H, 2-Hydroxymethyl-5,6,8-trimethoxy-4-prop-2Ј-enyloxynaphthalene
D2O exchangeable, 4-OH) ppm. 13C NMR: δ ϭ 30.2, 52.0, 55.9,
(17): To a slurry of LAH (170 mg, 4.5 mmol) in THF (10 mL) was
57.2, 62.9, 95.0, 114.4, 116.7, 119.6, 120.2, 121.3, 127.5, 136.1, added a solution of naphthoate 12 (1.0 g, 3.0 mmol) in THF
4420
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4416Ϫ4423

Synthesis of Ventiloquinone F and Isoventiloquinone F
FULL PAPER
(25 mL) dropwise at 25 °C. A similar protocol described earlier
after which water (120 mL) was added and the aqueous solution
afforded alcohol 17 (920 mg, 100%) as white crystals, m.p. 89Ϫ91 extracted with EtOAc. The residue obtained upon workup was
1
°C (from hexane Ϫ EtOAc). IR: ν˜ ϭ 3453 cmϪ1 (OH). H NMR: chromatographed with EtOAc/hexane (3:7) as eluent to yield an
3
δ ϭ 3.82, 3.98, 3.99 (each s, each 3 H), OCH3), 4.66 (dt, J ϭ 5.2,
inseparable mixture of the naphthopyrans 21 and 22 (456 mg, 71%)
4J ϭ 1.4 Hz, 2 H, 1Ј-H), 4.76 (s, 2 H, C2ϪCH2OH), 5.32 (dt, J ϭ as white cubes, m.p. 91Ϫ93 °C (from hexane). IR: ν˜ ϭ 1640 cmϪ1
3
4
3
4
1
3
10.6, J ϭ 1.4, 1 H, cis 3Ј-H), 5.57 (dt, J ϭ 17.2, J ϭ 1.4 Hz, 1
(CϭC). H NMR: δ ϭ 1.35 (d, J ϭ 6.4 Hz, 3 H, C3ϪCH3), 1.40
H, trans 3Ј-H), 6.20 (m, 1 H, 2Ј-H), 6.69 (s, 1 H, 7-H), 6.91 (d, (d, 3J ϭ 6.4 Hz, 3 H, C3ϪCH3), 1.62 (d, 3J ϭ 6.2 Hz, 3 H,
3J ϭ 1.2 Hz, 1 H, 3-H), 7.26 (s, 1 H, D2O exchangeable,
C2ϪCH2OH), 7.75 (d, 3J ϭ 1.2 Hz, 1 H, 1-H) ppm. 13C NMR:
δ ϭ 56.0, 57.8, 62.1, 65.9, 70.6, 96.8, 108.7, 113.0, 117.5, 121.6,
C1ϪCH3), 1.69 (d, 3J ϭ 6.2 Hz, 3 H, C1ϪCH3), 2.60 (dd, 2J ϭ
2
16.8, 3J ϭ 10.0 Hz, 1 H, 4-Hax), 2.66 (dd, J ϭ 16.8, 3J ϭ 10.0 Hz,
1 H, 4-Hax), 3.16 (dd, 2J ϭ 16.8, 3J ϭ 3.0 Hz, 1 H, 4-Heq), 3.18
123.5, 133.6, 136.2, 138.4, 150.0, 152.3, 155.2 ppm. C17H20O5 (dd, 2J ϭ 16.8, 3J ϭ 3.0 Hz, 1 H, 4-Heq), 3.77 (s, 6 H, OCH3), 3.80
(304.3): calcd. C 67.11, H 6.56; found C 67.40, H 6.91.
(m, 1 H, cis 3-H), 4.00 and 4.02 (each s, each 6 H, OCH3), 4.05
(m, 1 H, trans 3-H), 4.99 (m, 4 H, CH2Ph), 5.20 (q, J ϭ 6.2 Hz,
2 H, 1-H), 6.67 (s, 2 H, 8-H), 7.50 (m, 10 H, Ph), 7.74 (s, 1 H, 10-
H), 7.80 (s, 1 H, 10-H) ppm. C25H28O5 (408.5): calcd. C 73.53, H
6.86; found C 72.21, H 7.06.
3
5,6,8-Trimethoxy-4-(prop-2Ј-enyloxy)naphthalene-2-carbaldehyde
(18): The alcohol 17 (900 mg, 2.96 mmol) was oxidized with acti-
vated manganese dioxide (5 g) as described earlier to afford the
aldehyde 18 (500 mg, 56%) as yellow needles, m.p. 105Ϫ106 °C
1
(from hexane/EtOAc). IR: ν˜ ϭ 1675 cmϪ1 (CϭO). H NMR: δ ϭ
rac-(1R,3S)-5-Benzyloxy-3,4-dihydro-7-methoxy-1,3-dimethyl-1H-
naphtho[2,3-c]pyran-6,9-dione (23) and its (1R,3R) Diastereoisomer
25 and rac-(1R,3S)-5-benzyloxy-3,4-dihydro-9-methoxy-1,3-di-
methyl-1H-naphtho[2,3,-c]pyran-6,7-dione (24) and its (1R,3R) Dia-
stereoisomer 26: To a stirred solution of the pyrans 21 and 22
(450 mg, 1.10 mmol) in acetronile (80 mL) and water (25 mL) was
added a solution of cerium() ammonium nitrate (1220 mg,
2.22 mmol) in water (20 mL) dropwise over 8 min. After an ad-
ditional stirring (10 min), water (800 mL) was added and the aque-
ous solution was extracted with dichloromethane. The residue ob-
tained upon workup was chromatographed with EtOAc/hexane
(2:3) as eluent to afford two major fractions viz., a faster moving
one, Fraction A (192 mg, 46% comprising quinones 23 and 25) and
a slower moving one, Fraction B (171 mg, 42% comprising qui-
nones 24 and 26). Each fraction was again subjected to chromato-
graphic separation on a long column (1.0 m ϫ 15 mm ID) using
EtOAc/hexane (1:4) as eluent to afford the following:
3
4
3.82, 4.03, 4.04 (each s, each 3 H, OCH3), 4.72 (dt, J ϭ 3.6, J ϭ
3
4
1.6 Hz, 2 H, 1Ј-H), 5.34 (dt J ϭ 10.6, J ϭ 1.6 Hz, 1 H, cis 3Ј-
3
4
H), 5.60 (dt, J ϭ 17.2, J ϭ 1.6 Hz, 1 H, trans 3Ј-H), 6.20 (m, 1
H, 2Ј-H), 6.75 (s, 1 H, 7-H), 7.26 (d, J ϭ 1.4 Hz, 1 H, 3-H), 8.31
3
(d, 3J ϭ 1.4 Hz, 1 H, 1-H), 9.99 (s, 1 H, C2ϪCHO) ppm. 13C
NMR: δ ϭ 56.1, 57.2, 62.2, 70.2, 96.3, 102.9, 117.8, 122.0, 124.3,
125.2, 132.2, 133.0, 138.4, 153.6, 153.8, 155.5, 192.0 ppm.
C17H18O5(302.3): calcd. C 67.55, H 5.96; found C 67.75, H 5.86.
Alternative Route: Aldehyde 18 (840 mg, 2.78 mmol) was pyrolysed
at 180 °C as described earlier for 2 h. The crude phenol 19 was not
isolated but immediately benzylated as described before to yield the
same aldehyde 16 (620 mg, 57%) with identical physical properties
after chromatographic purification.
4-Benzyloxy-2-(1ЈЈ-hydroxyethyl)-5,6,8-trimethoxy-3-(prop-2Ј-enyl)-
naphthalene (20): To a freshly prepared solution of methylmag-
nesium iodide [Mg (88 mg, 3.64 mmol) and methyl iodide (516 mg,
3.64 mmol) in diethyl ether (20 mL)] was added the naphthaldehyde
16 (475 mg, 1.21 mmol) in diethyl ether (25 mL) dropwise. After an
additional 1 h of stirring at 25 °C, saturated aqueous ammonium
chloride was added dropwise to quench the reaction followed by
water (100 mL). The mixture was extracted with diethyl ether and
the residue obtained upon workup was chromatographed with
EtOAc/hexane (1:3) as eluent to afford the alcohol 20 (493 mg,
100%) as a clear thick oil. IR (film): ν˜ ϭ 3440 cmϪ1 (OH). 1H
Fraction A: The first isomer to elute was identified as the quinone
23 (92 mg, 22%), as yellow fluffy crystals, m.p. 191Ϫ193 °C (from
1
2-propanol). IR: ν˜ ϭ 1648 and 1688 cmϪ1 (CϭO). H NMR: δ ϭ
3
3
1.33 (d, J ϭ 6.2 Hz, 3 H, C3ϪCH3), 1.61 (d, J ϭ 6.6 Hz, 3 H,
C1ϪCH3), 2.42 (ddd, 2J ϭ 17.6, 3J ϭ 11.0, 5J ϭ 1.8 Hz, 1 H,
pseudoaxial 4-H), 2.90 (ddd, J ϭ 17.6, J ϭ 3.0, J ϭ 1.0 Hz, 1
H, pseudoequatorial 4-H), 3.68 (m, 1 H, 3-H), 3.90 (s, 3 H, OCH3),
4.85 (ddq, 3J ϭ 6.6, 5J ϭ 1.8, 5J ϭ 1.0 Hz, 1 H, 1-H), 4.88 (d, 2J ϭ
2
3
5
2
10.2 Hz, 1 H, CH2Ph), 5.02 (d, J ϭ 10.2 Hz, 1 H, CH2Ph), 6.13
3
NMR: δ ϭ 1.57 (d, J ϭ 6.6 Hz, 3 H, C2ϪCHCH3), 1.83 (s, 1 H,
(s, 1 H, 8-H), 7.45 (m, 5 H, Ph), 7.73 (s, 1 H, 10-H) ppm. 13C
NMR: δ ϭ 21.4, 21.8, 31.7, 59.6, 70.2, 73.2, 75.7, 108.6, 119.1,
121.3, 128.5, 128.6, 128.8 (ϫ 3), 131.9, 136.5, 136.9, 148.2, 157.0,
161.0, 178.9, 184.6 ppm. C23H22O5 (378.1): calcd. C 73.02, H 5.82;
found C 73.26, H 6.10.
3
D2O exchangeable, C2ϪCH(OH)CH3], 3.70 (dt, J ϭ 5.6, 4J ϭ 1.8
Hz, 2 H, 1Ј-H), 3.73 (s, 3 H, OCH3), 4.02 (s, 6 H, 2 ϫ OCH3), 4.87
(dt, 3J ϭ 17.8, 4J ϭ 1.8 Hz, 1 H, trans 3Ј-H), 4.96 (s, 2 H, CH2Ph),
3
4
3
5.06 (dt, J ϭ 10.2, J ϭ 1.8 Hz, 1 H, cis 3Ј-H), 5.21 (q, J ϭ 6.6,
1ЈЈ-H), 6.15 (m, 1 H, 2Ј-H), 6.69 (s, 1 H, 7-H), 7.47 (m, 5 H, Ph),
8.25 (s, 1 H, 1-H) ppm. 13C NMR: δ ϭ 24.7, 29.9, 55.9, 57.3, 62.4,
66.8, 76.9, 95.0, 114.9, 115.4, 122.5, 123.3, 127.7, 128.6 (ϫ 4),
128.9, 136.4, 138.2, 138.3, 141.0, 150.1, 151.4, 152.8 ppm.
C25H27O5 (407.5): calcd. C 73.71, H 6.63; found C 74.52; H 6.93.
The second isomer to elute was identified as the quinone 25 (98 mg,
24%), as yellow crystals, m.p. 208Ϫ210 °C (from 2-propanol). IR:
ν˜ ϭ 1649 and 1690 cmϪ1 (CϭO). UV (ethanol): λmax. (ε) ϭ
1
3
251 (4.82), 286 (4.08), 359 nm (3.55). H NMR: δ ϭ 1.28 (d, J ϭ
6.2 Hz, 3 H, C3ϪCH3), 1.56 (d, 3J ϭ 7.0 Hz, 3 H, C1ϪCH3), 2.37
(ddd, 2J ϭ 17.6, 3J ϭ 9.4, 5J ϭ 1.0 Hz, 1 H, pseudoaxial 4-H), 2.90
rac-(1R,3S)-(5-Benzyloxy-3,4-dihydro-6,7,9-trimethoxy-1,3-di-
2
3
methyl-1H-naphtho[2,3-c]pyran (21) and its (1R,3R) Diastereoisomer (dd, J ϭ 17.6, J ϭ 3.8 Hz, 1 H, pseudoequatorial 4-H), 3.91 (s,
22: To a solution of the naphthyl alcohol 20 (640 mg, 1.57 mmol)
3 H, OCH3), 3.95 (m, 1 H, 3-H), 4.90 (d, 2J ϭ 10.4 Hz, 1 H,
in THF (35 mL) and water (25 mL) was added mercury() acetate CH2Ph), 4.95 (dq, J ϭ 7.0, J ϭ 1.0 Hz, 1 H, 1-H), 5.00 (d, J ϭ
3
5
2
(500 mg; 1.57 mmol) and the resulting mixture was stirred at 20 °C
for 1 h after which aqueous sodium hydroxide (12 mL of a 5 
solution) was added and stirring maintained for an additional 1 h
at 20 °C. An additional aliquot of sodium hydroxide (12 mL of a 5
 solution) was added together with sodium borohydride (1541 mg,
10.4 Hz, 1 H, CH2Ph), 6.13 (s, 1 H, 8-H), 7.49 (m, 5 H, Ph), 7.66
(s, 1 H, 10-H) ppm. 13C NMR: δ ϭ 21.0, 21.5, 30.9, 59.6, 63.6,
70.7, 75.9, 108.6, 119.1, 119.9, 128.5, 128.7, 128.8 (ϫ 3), 131.8,
135.8, 136.9, 148.0, 157.3, 161.0, 178.9, 184.6 ppm. C23H22O5
(378.1): calcd. C 73.02, H 5.82; found C 73.25, H 6.13. HR MS
40.8 mmol) and the resulting reaction mixture was stirred for 1 h (C23H22O5): calcd. 378.1467; found 378.1471.
Eur. J. Org. Chem. 2004, 4416Ϫ4423
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4421

R. G. F. Giles, I. R. Green, N. van Eeden
FULL PAPER
3
2
Fraction B: The first isomer to elute was identified as the quinone
24 (73 mg, 18%) as bright yellow crystals, m.p. 191Ϫ193 °C (from
C3ϪCH3), 1.54 (d, J ϭ 6.6 Hz, 3 H, C1ϪCH3), 2.43 (ddd, J ϭ
17.5, 3J ϭ 10.9, 5J ϭ 2.2 Hz, 1 H, pseudoaxial 4-H), 2.83 (ddd,
2J ϭ 17.5, 3J ϭ 3.0, 5J ϭ 1.7 Hz, 1 H, pseudoequatorial 4-H), 3.75
2-propanol). IR: ν˜ ϭ 1660 and 1709 cmϪ1 (CϭO). H NMR: δ ϭ
1
1.33 (d, J ϭ 6.2 Hz, 3 H, C3ϪCH3), 1.59 (d, J ϭ 6.6 Hz, 3 H, (ddq, 3J ϭ 10.9, 3J ϭ 6.2, 3J ϭ 3.0 Hz, 1 H, 3-H), 3.95 (s, 3 H,
3
3
C1ϪCH3), 2.38 (ddd, 2J ϭ 17.4, 3J ϭ 9.8, 5J ϭ 1.5 Hz, 1 H,
OCH3), 4.77 (ddq, 3J ϭ 6.6, 5J ϭ 2.2, 5J ϭ 1.7 Hz, 1 H, 1-H), 5.87
2
3
5
pseudoaxial 4-H), 2.85 (ddd, J ϭ 17.4, J ϭ 3.2, J ϭ 1.5 Hz, 1 (s, 1 H, 8-H), 7.18 (s, 1 H, 10-H), 12.18 (s, D2O exchangeable, 1 H,
H, pseudoequatorial 4-H), 3.68 (m, 1 H, 3-H), 3.99 (s, 3 H, OCH3),
5-OH) ppm. 13C NMR: δ ϭ 21.1, 21.8, 30.6, 56.6, 70.0, 73.3, 110.5,
3
5
2
4.86 (tq, J ϭ 6.6, J ϭ 1.5 Hz, 1 H, 1-H), 4.87 (d, J ϭ 10.2 Hz,
111.9, 115.3, 116.1, 129.5, 149.3, 159.9, 160.3, 184.1, 184.8 ppm.
2
1 H, CH2Ph), 5.00 (d, J ϭ 10.2 Hz, 1 H, CH2Ph), 5.96 (s, 1 H, 8- C16H16O6 (288.1): calcd. C 66.66, H 5.59; found C 66.40, H 5.35.
H), 7.20 (m, 3 H, 3Ј-, 4Ј- and 5Ј-H of aryl ring), 7.46 (s, 1 H, 10 HR MS (C16H16O5): calcd. 288.0998; found 288.1002.
H), 7.60 (m, 2 H, 2Ј- and 6Ј-H of aryl ring) ppm. 13C NMR: δ ϭ Further elution afforded isoventiloquinone F (8, 126 mg, 46%) as
21.2, 21.6, 30.6, 56.9, 63.7, 70.8, 76.1, 102.8, 117.4, 118.1, 128.5,
128.6, 129.0 (ϫ 2), 131.1, 133.7, 134.4, 136.8, 148.5, 148.8, 160.0,
178.9, 179.9 ppm. C23H22O5 (378.1): calcd. C 73.02, H, 5.82; found
C 73.36, H 6.10.
fine yellow crystals, m.p. 225Ϫ226 °C (from EtOAc/hexane). IR:
1
ν˜ ϭ 3696 cmϪ1 (OH), 1643 and 1663 cmϪ1 (CϭO). H NMR: δ ϭ
3
3
1.36 (d, J ϭ 6.4 Hz, 3 H, C3ϪCH3), 1.56 (d, J ϭ 6.6 Hz, 3 H,
C1ϪCH3), 2.44 (ddd, 2J ϭ 17.6, 3J ϭ 9.4, 5J ϭ 1.0 Hz, 1 H,
pseudoaxial 4-H), 2.91 (dd, J ϭ 17.6, J ϭ 3.4, pseudoequatorial
4-H), 3.91 (s, 3 H, OCH3), 4.05 (m, 1 H, 3-H), 5.03 (dq, J ϭ 6.6,
2
3
The second isomer to elute was identified as the quinone 26 (98 mg,
24%) as bright yellow crystals, m.p. 208Ϫ210 °C (from 2-propanol):
3
IR: ν˜ ϭ 1660 and 1709 cmϪ1 (CϭO). UV (ethanol): λmax. (ε) ϭ 5J ϭ 1.0 Hz, 1 H, 1-H), 6.12 (s, 1 H, 8-H), 7.33 (s, 1 H, 10-H),
1
3
260 (4.35), 288 (3.90), 372 nm (3.50). H NMR: δ ϭ 1.28 (d, J ϭ 12.16 (s, D2O exchangeable, 1 H, 5-OH), 13C NMR: δ ϭ 21.2, 21.4,
5.8 Hz, 3 H, C3ϪCH3), 1.56 (d, 3J ϭ 7.0 Hz, 3 H, C1ϪCH3), 2.33 29.8, 56.6, 63.2, 71.0, 110.5, 111.8, 116.1, 117.1, 129.3, 149.2, 160.2,
(ddd, 2J ϭ 17.2, 3J ϭ 9.6, 5J ϭ 1.0 Hz, 1 H, pseudoaxial 4-H), 2.86
160.4, 184.1, 184.7 ppm. C16H16O5 (288.1): calcd. C 66.66, H 5.59;
found 66.41, 5.34. C16H16O5: calcd. 288.0998; found
1 H, 3-H), 4.00 (s, 3 H, OCH3), 4.89 (d, 2J ϭ 10.4 Hz, 1 H, CH2Ph), 288.1003 (HRMS).
2
3
(dd, J ϭ 17.2, J ϭ 3.2 Hz, 1 H, pseudoequatorial 4-H), 3.95 (m,
C
H
2
3
5
5.01 (d, J ϭ 10.4 Hz, 1 H, CH2Ph), 5.02 (dq, J ϭ 7.0, J ϭ 1.0
Hz, 1 H, 1-H), 5.97 (s, 1 H, 8-H), 7.39 (m, 3 H, 3Ј, 4Ј,5Ј-H of aryl
ring), 7.40 (s, 1 H, 10-H), 7.55 (m, 2 H, 2Ј,6Ј-H of aryl ring) ppm.
13C NMR: δ ϭ 21.2, 21.6, 30.6, 56.9, 63.6, 70.7, 76.0, 102.6, 117.4,
118.1, 128.5, 128.6, 129.0 (ϫ 2), 131.1, 133.6, 134.4, 136.8, 148.4,
148.7, 159.7, 178.8, 179.8. HR MS (C23H22O5): calcd. 378.1467;
found 378.1476.
rac-(1R,3R)-5-Benzyloxy-7-hydroxy-1,3-dimethyl-1H-naphtho[2,3-
c]pyran-6,9-dione (29): solution of quinone 26 (300 mg,
A
0.83 mmol) in EtOAc (100 mL) containing palladium catalyst (10%
on C, 90 mg) and two drops of concentrated HCl solution was
hydrogenated at 20 °C until 2 mol equivalent of hydrogen had been
absorbed. Filtration of the reaction mixture and removal of the
solvent produced a yellow clay which upon careful recrystallisation
from ethanol afforded fine olive yellow crystals of quinone 29
(100 mg, 33%), m.p. 195Ϫ196 °C. IR: ν˜ ϭ 3350 cmϪ1 (OH), 1667
cmϪ1 (CϭO). UV (ethanol): λmax. (ε) ϭ 258 (4.18), 281 (4.19),
355 nm (3.52). 1H NMR: δ ϭ 1.29 (d, 3J ϭ 6.2 Hz, 3 H, C3ϪCH3),
1.56 (d, 3J ϭ 6.6 Hz, 3 H, C1ϪCH3), 2.36 (dd, 2J ϭ 17.4, 3J ϭ 9.2
3-Ethyl-1-hydroxy-2-(2Ј-hydroxypropyl)-7-methoxy-5,8-naphtho-
quinone (28): A mixture of the quinones 23 and 25 (192 mg,
0.51 mmol) in ethyl acetate (30 mL) containing palladium catalyst
(10% on C, 40 mg) was hydrogenated for 24 h and the residue ob-
tained after filtration of catalyst and removal of solvent was chrom-
atographed with EtOAc/hexane (1:1) as eluent to yield a mixture
of the quinone 7 and 8 (63 mg, 43%; see later). Further elution
afforded the ring-opened naphthoquinone 28 (59 mg, 40%) as yel-
low crystals, m.p. 142Ϫ144 °C (from EtOAc). IR: ν˜ ϭ 3402 (OH),
1661 cmϪ1 (CϭO). UV (ethanol): λmax. (ε) ϭ 251 (4.05), 296 (4.07),
423 nm (3.63). 1H NMR: δ ϭ 1.25 (t, 3J ϭ 7.8 Hz, 3 H, CH2CH3),
1.32 (d, 3J ϭ 6.2 Hz, 3 H, CH2CH(OH)CH3], 1.90 (s, D2O ex-
2
3
Hz, 1 H, pseudoaxial 4-H), 2.89 (dd, J ϭ 17.4, J ϭ 3.2 Hz, 1 H,
2
pseudoaxial 4-H), 3.94 (m, 1 H, 3-H), 4.92 (d, J ϭ 10.2 Hz, 1 H,
CH2Ph), 5.00 (d, 2J ϭ 10.2 Hz, 1 H, CH2Ph), 5.07 (q, 3J ϭ 6.6 Hz,
1 H, 1-H), 6.32 (s, 1 H, 8-H), 7.41 (m, 3 H, 3Ј-, 4Ј-, and 5Ј-H of
aryl ring), 7.52 (m, 2 H, 2Ј- and 6Ј-H of aryl ring), 7.69 (br. s, one
D2O exchangeable H, 2 H, 7-OH and 10-H) ppm. 13C NMR: δ ϭ
21.2, 21.5, 30.8, 63.6, 70.8, 76.0, 109.2, 120.5, 128.5 (ϫ 2), 128.7
(ϫ 2), 129.7, 132.6, 135.4 (ϫ 2), 136.7, 149.4, 156.9, 157.5, 180.3,
184.6 ppm. C22H20O5 (364.1): calcd. C 72.53, H 5.53; found C
72.91, H 5.63. HR MS (C22H20O5): calcd. 364.1311; found
364.1312.
3
changeable, 1 H, CH2CH(OH)CH3], 2.80 (dq, 2J ϭ 7.8, J ϭ 7.6
3
Hz, 2 H, CH2CH3), 2.93 [d, J ϭ 6.6 Hz, 2 H, CH2CH(OH)CH3],
3.90 (s, 3 H, OCH3), 4.15 [m, 1 H, CH2CH(OH)CH3], 6.09 (s, 1 H,
6-H), 7.51 (s, 1 H, 4-H), 12.32 (s, D2O exchangeable, 1 H, 1-OH)
ppm. 13C NMR: δ ϭ 14.0, 23.4, 26.4, 34.7, 56.0, 67.5, 109.8, 111.4,
119.2, 129.3, 131.7, 153.3, 159.7, 160.4, 183.5, 184.2 ppm.
C16H18O5 (290.1): calcd. C 66.20, H 6.25; found C 66.40, H 6.35.
HR MS (C16H18O5): calcd. 290.1154; found 290.1163.
Acknowledgments
rac-(1R,3S)-3,4-Dihydro-5-hydroxy-7-methoxy-1,3-dimethyl-1H-
naphtho[2,3-c]pyran- 6,9-dione (7) (Ventiloquinone F) and the rac-
(1R,3R) Diastereoisomer 8 (Isoventiloquinone F): A mixture of the
quinones 23 and 25 (362 mg, 0.96 mmol) in EtOAc (30 mL) con-
taining palladium catalyst (10% on C, 40 mg) was hydrogenated at
20 °C until 2 mol equivalents of H2 had been adsorbed. Removal
of the solvent after filtration of the catalyst afforded a residue
which was chromatographed on a long column (1.0 m ϫ 15 mm
ID) using EtOAc/hexane (1:4) as eluent to give ventiloquinone F
(7, 121 mg, 44%) as fine yellow crystals, m.p. 197Ϫ199 °C (from
EtOAc/hexane) (ref.[2] m.p. 213 °C). IR: ν˜ ϭ 3696 (OH), 1642 and
1664 cmϪ1 (CϭO). 1H NMR: δ ϭ 1.38 (d, 3J ϭ 6.2 Hz, 3 H,
This work was supported by the National Research Foundation
and the University of the Western Cape.
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