Synthetic approaches to sporochnols A-C

Article abstract of DOI:10.1081/SCC-200061679

Formal total synthesis of sporochnols A-C, hydroxyphenyl substituted monoterpenes isolated from the Caribbean brown alga Sporochnus bolleanus exhibiting feeding deterrent property toward herbivorous fish, is described. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200061679

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Synthetic Approaches to
Sporochnols A–C
A. Srikrishna a , G. Satyanarayana a & M. R. Prasad a
a Department of Organic Chemistry , Indian Institute
of Science , Bangalore, India
Published online: 16 Aug 2006.
To cite this article: A. Srikrishna , G. Satyanarayana & M. R. Prasad (2005) Synthetic
Approaches to Sporochnols A–C, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 35:12, 1687-1698, DOI:
10.1081/SCC-200061679
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Synthetic Communicationsw, 35: 1687–1698, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200061679
Synthetic Approaches to Sporochnols A–C
A. Srikrishna, G. Satyanarayana, and M. R. Prasad
Department of Organic Chemistry, Indian Institute of Science,
Bangalore, India
Abstract: Formal total synthesis of sporochnols A–C, hydroxyphenyl substituted
monoterpenes isolated from the Caribbean brown alga Sporochnus bolleanus exhi-
biting feeding deterrent property toward herbivorous fish, is described.
Keywords: Sporochnols, sesquiterpene, Claisen rearrangement
In a variety of marine organisms, chemical defense is common phenomenon
as part of the self-defense mechanism to protect themselves from higher
animals. During their investigations on the families of chemically
defended tropical marine algae, Shen et al.[1] have reported the isolation
and structure elucidation of one major, sporochnol A 1, and two minor,
sporochnols B 2 and C 3, metabolites from the brown alga Sporochnus
bolleanus, which was found to be rejected by the Caribbean surgeon fish.
It was found that the major metabolite sporochnol A 1, when incorporated
into a palatable food, deterred feeding by a mixed species group of
herbivorous Caribbean parrotfishes. Structures of sporochnols A–C 1–3
were established from their spectral data, and compounds 2 and 3 were
found to be 1:1 mixtures of diastereomers. Feeding deterrence toward herbi-
vorous fish exhibited by sporochnol A made the compounds 1–3 interesting
Received in India February 11, 2005
Address correspondence to A. Srikrishna, Department of Organic Chemistry, Indian
Institute of Science, Bangalore 560 012, India. Fax: 91-80-23600683; 23600529;
E-mail: ask@orgchem.iisc.ernet.in
1687

1688
A. Srikrishna, G. Satyanarayana, and M. R. Prasad
synthetic targets.[2] Herein, we report our approaches toward the synthesis
of sporochnols A–C 1–3.
It was contemplated that sporochnols A–C 1–3 could be obtained
from the pentenoate 4 via alkylation with dimethylallyl bromide followed
by decarboxylation and hydrolysis of the methyl ether. The pentenoate 4,
containing the requisite quaternary carbon atom, could be obtained from the
acetophenone 5 via the cinnamyl alcohol 6 employing a Claisen rearrange-
ment–based methodology, Scheme 1.
The synthetic sequence starting from 4-methoxyacetophenone 5 is
depicted in Schemes 2 and 3. First, synthesis of the pentenoate 4 was accom-
plished via the alcohol 6. Thus, Horner–Wadsworth–Emmons reaction of the
acetophenone 5 with triethyl phosphonoacetate and sodium hydride in
refluxing THF furnished a 9:1 E,Z-mixture of the cinnamate 7 in 95% yield.
Regioselective reduction with lithium aluminium hydride (LAH) in ether at
a low temperature transformed the cinnamate 7 into the allyl alcohol 6 in
97% yield. Johnsons’ one-pot ortho ester variation[3] of the Claisen rearrange-
ment was employed for the conversion of the allyl alcohol 6 into the penteno-
ate 4. Thermal activation of the allyl alcohol 6 with triethyl orthoacetate and a
catalytic amount of propionic acid in a sealed tube at 1808C for 48 h furnished
the pentenoate 4 in 69% yield, creating the requisite quaternary carbon atom,
whose structure was established from its spectral data. Generation of enolate
of the ester 4 with lithium diisopropylamide (LDA) in THF at 2708C and
alkylating with dimethylallyl bromide furnished the hexenoate 8 in 74%
Scheme 1.

Synthetic Approaches to Sporochnols A–C
1689
Scheme 2. Reagents, conditions, and yields: (a) (EtO)2P(O)CH2COOEt, NaH, THF,
reflux, 10 h, 95%; (b) LAH, Et2O, 2708C ! 2 208C, 1 h, 97%; (c) CH3C(OEt)3,
EtCOOH, sealed tube, 1808C, 48 h, 69%; (d) LDA, THF, 2708C ! RT,
Me2C55CHCH2Br, 16 h, 74%; (e) 20% KOH in MeOH, reflux, 48 h; (f) i. (COCl)2,
C6H6, RT, 2 h; ii. N-hydroxypyridine-2-thione Na salt, C6H6, DMAP, reflux, 1 h; (g)
nBu3SnH, C6H6, AIBN, reflux, 14 h; 36% (from the ester 8).
yield. Next, attention was turned to decarboxylation for the conversion of the
hexenoate 8 into the methyl ether 9 of sporochnol A, and Barton’s radical-
mediated decarboxylation method[4] was chosen. Base-catalyzed hydrolysis
of the hexenoate 8 furnished the acid 10, which was converted into the
N-hydroxypyridinethione ester 11 via the corresponding acid chloride.
Treatment of the ester 11 with tributyltin hydride in the presence of azobisi-
sobutyronitrile (AIBN) in refluxing benzene, however, failed to produce the
expected product 9, and generated the rearrangement product 12, whose
structure was deduced from the spectral data, in particular 1H and 13C NMR.

1690
A. Srikrishna, G. Satyanarayana, and M. R. Prasad
Scheme 3. Reagents, conditions, and yields: (a) LAH, Et2O, 08C, 1 h, 92%; (b) PCC,
silica gel, CH2Cl2, RT, 0.5 h, 88%; (c) Ph3P55CHOMe, THF, 08C ! RT, 40 min, 70%;
(d) 3 N HCl, THF, RT, 1.5 h, 87%; (e) Ph3P55CMe2, THF, RT, 1 h, 78%; (f) reference 2 g.
Formation of the diene 12 from the ester 11 can be readily explained as
shown in Scheme 4. The homoallyl radical 13 formed from the ester 11
undergoes 3-exo trig cyclization to generate the cyclopropylmethyl radical
14. Opening of the cyclopropylmethyl radical 14 generates the more stable
benzylic radical 15, which abstracts hydrogen from tinhydride leading to
the diene 12.[5] Generation of the rearranged product 12 in the radical-
mediated decarboxylation prompted us to alter the strategy, and a homologa-
tion and Wittig reaction was contemplated for the conversion of the
pentenoate 4 into the diene 9, which is depicted in Scheme 3. The ester 4
was converted into the aldehyde 16 employing a two-step protocol. Thus,
Scheme 4.

Synthetic Approaches to Sporochnols A–C
1691
reduction of the pentenoate 4 with LAH in ether furnished the alcohol 17,
which upon oxidation with pyridinium chlorochromate (PCC) and silica gel
in methylene chloride generated the pentenal 16 in 81% yield. Wittig
reaction of the aldehyde 16 with methoxymethylenetriphenylphosphorane
followed by hydrolysis of the resultant enol ether 18 with 3N hydrochloric
acid furnished the hexenal 19 in 61% yield. Finally, Wittig reaction with
isopropylidinetriphenylphosphorane in THF transformed the hexenal 19 into
sporochnol A methyl ether 9 in 78% yield, which exhibited spectral data
identical to that reported in the literature. Because the conversion of the
ether 9 into sporochnols A–C 1–3 has already been reported,[2g] the present
sequence constitutes the formal total synthesis of sporochnols A–C.
In conclusion, we have developed an efficient methodology for
the synthesis of sporochnols A–C, which can be extended to several
analogues.1
EXPERIMENTAL
IR spectra were recorded on a Jasco FTIR 410 spectrophotometer.
1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded on JNM
l-300 spectrometer, using 1:1 mixture of CDCl3 and CCl4 as solvent. The
chemical shifts (d ppm) and coupling constants (Hz) are reported in the
1
standard fashion with reference to either internal tetramethylsilane (for H)
or the central line (77.0 ppm) of CDCl3 (for 13C). In the 13C NMR spectra,
1Synthesis of a keto analogue I of sporochnols has also been accomplished in ꢀ35%
yield starting from the alcohol 17 via the bromide as depicted. Spectral data for the
ketone I: IR (neat): nmax/cm21 1712, 1609, 1512, 915. 1H NMR (300 MHz,
CDCl3 þ CCl4): d 7.16 (2 H, d, J 8.7 Hz, H-20 and 60), 6.78 (2 H, d, J 8.7 Hz, H-30
and 50), 5.94 (1 H, dd, J 17.7 and 10.8 Hz, H-7), 5.07 (1 H, dd, J 10.8 and 0.9 Hz),
and 5.02 (1 H, dd, J 17.7 and 0.9 Hz) [H-8], 3.77 (3 H, s, OCH3), 2.47 (1 H, septet,
J 6.9 Hz), 2.35–2.10 (2 H, m, H-4), 2.10–1.85 (2 H, m, H-5), 1.32 (3 H, s, tert-
CH3), 1.01 (3 H, d, J 6.9 Hz), and 1.02 (3 H, d, J 6.9 Hz) [CH(CH3)2]. 13C NMR
(75 MHz, CDCl3 þ CCl4): d 213.4 (C, C-3), 157.8 (C, C-40), 146.7 (CH, C-7), 138.4
(C, C-10), 127.6 (2 C, CH, C-20 and 60), 113.6 (2 C, CH, C-30 and 50), 112.1 (CH2,
C-8), 55.0 (CH3, OMe), 43.3 (C, C-6), 40.9 (CH, C-2), 36.0 (CH2), 34.2 (CH2, tert-
CH3), 25.5 (CH3), 18.4 [2 C, CH3, CH(CH3)2].

1692
A. Srikrishna, G. Satyanarayana, and M. R. Prasad
the nature of the carbons (C, CH, CH2, or CH3) was determined by recording
DEPT-135 spectra and is given in parentheses. Low-resolution mass spectra
were recorded using Shimadzu QP-5050A GCMS instrument using direct
inlet mode. Relative intensities are given in parentheses. High-resolution
mass spectra were recorded on a Micromass Q-TOF micromass spectrometer
using electron spray ionization mode.
Ethyl E-3-(4-methoxyphenyl)but-2-enoate (7): A suspension of sodium
hydride (667 mg, 60% dispersion in oil, 16.7 mmol) in hexanes under
nitrogen atmosphere was magnetically stirred for 10 min and the solvent
was syringed out. The oil-free NaH was then suspended in dry THF (4 ml)
and cooled in an ice bath. Triethyl phosphonoacetate (3.43 ml, 17.3 mmol)
was added dropwise and the reaction mixture was stirred for 30 min at rt. A
solution of 4-methoxyacetophenone 5 (1 g, 6.7 mmol) in dry THF (2 ml)
was added dropwise to the reaction mixture and refluxed for 10 h. It was
cooled, quenched by careful addition of saturated aqueous NH4Cl solution,
and extracted with ether (4 ꢁ 5 ml). The ether extract was washed with
brine and dried (Na2SO4). Evaporation of the solvent and purification of the
residue over a silica-gel column using ethyl acetate–hexane (1:20) as eluent
furnished 9:1 diastereomers of the cinnamate 7 (1.4 g, 95%) as oil. IR (neat):
nmax/cm21 1711, 1626, 1604, 1574, 1513. 1H NMR (300 MHz,
CDCl3 þ CCl4): peaks resulting from the major isomer d 7.42 (2 H, d, J
8.7 Hz, H-20 and 60), 6.84 (2 H, d, J 8.7 Hz, H-30 and 50), 6.06 (1 H, s, H-2),
4.18 (2 H, q, J 7.2 Hz, OCH2CH3), 3.81 (3 H, s, OCH3), 2.55 (3 H, s, H-4),
1.31 (3 H, t, J 7.2 Hz, OCH2CH3). Peaks resulting from the minor isomer: d
7.14 (2 H, d, J 8.7 Hz, H-20 and 60), 6.82 (2 H, d, J 8.7 Hz, H-30 and 50),
5.82 (1 H, s, H-2), 4.02 (2 H, q, J 7.2 Hz, OCH2CH3), 3.80 (3 H, s, OCH3),
2.16 (3 H, s, H-4), 1.14 (3 H, t, J 7.2 Hz, OCH2CH3). 13C NMR (75 MHz,
CDCl3 þ CCl4): d 166.5 (C, OC55O), 160.4 (C, C-3), 154.7 (C, C-40), 134.4
(C, C-10), 127.6 (2 C, CH, C-20 and 60), 115.4 (CH, C-2), 113.8 (2 C, CH,
C-30 and 50), 59.4 (CH2, OCH2CH3), 55.1 (CH3, OMe), 17.7 (CH3, C-4),
14.5 (CH3, OCH2CH3). Peaks resulting from the minor isomer: d 165.7
(C, OC55O), 159.5 (C, C-3), 154.5 (C, C-40), 132.6 (C, C-10), 128.6 (2 C,
CH, C-20 and 60), 117.2 (CH, C-2), 113.2 (2 C, CH, C-30 and 50), 59.5
(CH2, OCH2CH3), 55.0 (CH3, OMe), 27.4 (CH3, C-4), 14.3 (CH3,
OCH2CH3). Mass: m/z 220 (Mþ, 97%), 175 (100), 174 (45), 148 (82), 115
(28), 103 (20), 91 (32).
E-3-(4-methoxyphenyl)but-2-enol (6): To a cold (2908C), magnetically
stirred solution of the cinnamate 7 (1.05 g, 4.8 mmol) in dry ether (10 ml)
was added LAH (181 mg, 4.8 mmol) and stirred for 1 h. The reaction
mixture was then diluted with ether (30 ml) and carefully quenched with
water (5 ml). The organic layer was separated and the aqueous phase
extracted with ether (20 ml). The combined organic phase was washed with
brine and dried (Na2SO4). Evaporation of the solvent and purification of the

Synthetic Approaches to Sporochnols A–C
1693
residue over a silica-gel column using ethyl acetate–hexane (1:20 to 1:5) as
eluent furnished the alcohol 6 (848 mg, 99%) as a colorless solid.[6] Mp
1
51–538C. IR (neat): nmax/cm21 3340, 3247, 1607, 1514, 1029. H NMR
(300 MHz, CDCl3 þ CCl4): d 7.28 (2 H, d, J 8.7 Hz, H-20 and 60), 6.78 (2
H, d, J 8.7 Hz, H-30 and 50), 5.86 (1 H, t, J 6.6 Hz, H-2), 4.28 (2 H, d, J
6.6 Hz, CH2OH), 3.78 (3 H, s, OCH3), 2.02 (3 H, s, H-4), 1.86 (1 H, brs).
13C NMR (75 MHz, CDCl3 þ CCl4): d 159.0 (C, C-40), 137.2 (C), 135.3
(C), 126.8 (2 C, CH, C-20 and 60), 125.0 (CH, C-2), 113.6 (2 C, CH, C-30
and 50), 59.8 (CH2, OCH2), 55.0 (CH3, OMe), 16.0 (CH3, C-4). Mass: 178
(Mþ, 31%), 163 (21), 136 (10), 135 (100), 121 (15), 105 (15), 91 (20).
Ethyl 3-methyl-3-(4-methoxyphenyl)pent-4-enoate (4): A solution of the
allyl alcohol 6 (1 g, 5.6 mmol), triethyl orthoacetate (5 ml, 28.1 mmol), and
a catalytic amount of propionic acid was placed in a sealed tube and heated
to 1808C for 2 days in an oil bath. The reaction mixture was then cooled,
diluted with ether (10 ml), washed with 3 N of aqueous HCl (10 ml),
followed by saturated NaHCO3 solution (10 ml) and brine, and dried
(Na2SO4). Evaporation of the solvent and purification of the residue over a
silica-gel column using ethyl acetate–hexane (1:50) as eluent furnished the
pentenoate 4 (960 mg, 69%) as oil. IR (neat): nmax/cm21 1734, 1609, 1512,
1
917. H NMR (300 MHz, CDCl3 þ CCl4): d 7.18 (2 H, d, J 8.7 Hz, H-20 and
60), 6.77 (2 H, d, J 8.7 Hz, H-30 and 50), 6.10 (1 H, dd, J 17.4 and 10.5 Hz,
H-4), 5.08 (1 H, d, J 10.5 Hz) and 5.02 (1 H, d, J 17.4 Hz) [H-5], 3.96 (2 H,
q, J 7.2 Hz, OCH2CH3), 3.75 (3 H, s, OCH3), 2.72 and 2.66 (2 H, AB q, J
13.8 Hz, H-2), 1.52 (3 H, s, tert-CH3), 1.10 (3 H, t, J 7.2 Hz, OCH2CH3).
13C NMR (75 MHz, CDCl3 þ CCl4): d 170.8 (C, OC55O), 157.9 (C, C-40),
146.0 (CH, C-4), 137.9 (C, C-10), 127.4 (2 C, CH, C-20 and 60), 113.4 (2 C,
CH, C-30 and 50), 112.0 (CH2, C-5), 59.8 (CH2, OCH2), 54.9 (CH3, OMe),
45.7 (CH2, C-2), 42.9 (C, C-3), 25.7 (CH3, tert-CH3), 14.2 (CH3,
OCH2CH3). Mass: 248 (Mþ, 8%), 162 (12), 161 (100), 91 (14). HRMS:
m/z calcd. for C15H20O3Na (M þ Na): 271.1310. Found: 271.1306.
Ethyl 2-[2-(4-methoxyphenyl)but-3-en-2-yl]-5-methylhex-4-enoate (8):
To a cold (2708C), magnetically stirred solution of LDA [prepared from dii-
sopropylamine (0.28 ml, 2.03 mmol) and BuLi (2.4 M in hexane, 0.81 ml,
n
1.9 mmol)] in dry THF (3 ml) was added a solution of the ester 4 (100 mg,
0.4 mmol) in dry THF (2 ml), and the reaction mixture stirred for 40 min at
the same temperature. The enolate thus formed was treated with prenyl
bromide (0.24 ml, 2.03 mmol) and stirred for 16 h at rt. It was then diluted
with water (5 ml) and extracted with ether (2 ꢁ 10 ml). The combined ether
extract was washed with 3 N of HCl, followed by brine, and dried
(Na2SO4). Evaporation of the solvent and purification of the residue over a
silica-gel column using ethyl acetate–hexane (1:49) as eluent furnished a 2:1
diastereomeric mixture of the ester 8 (70 mg, 74% based on starting
1
material consumed). IR (neat): nmax/cm21 1732, 1726, 1611, 1513, 919. H

1694
A. Srikrishna, G. Satyanarayana, and M. R. Prasad
NMR (300 MHz, CDCl3 þ CCl4, 2:1 mixture of diastereomers): d 7.26–7.18 (2
H, m, H-200 and 600), 6.60–6.40 (2 H, m, H-300 and 500), 6.35 (dd, J 17.7 and
10.8 Hz) and 6.15 (dd, J 17.1 and 10.5 Hz) [1 H, H-30], 5.22–4.90 (3 H, m,
H-4 and 40), 4.10–3.60 (2 H, m, OCH2), 3.76 and 3.75 (3 H, s, OCH3),
2.82–2.60 (1 H, m), 2.42–1.50 (2 H, m), 1.63 (3 H, s) and 1.47 (3 H, s)
[2 ꢁ olefinic CH3], 1.47 (3 H, s, tert-CH3), 1.09 (t, J 7.2 Hz) and 0.97 (t, J
6.9 Hz) [3 H, OCH2CH3]. 13C NMR (75 MHz, CDCl3 þ CCl4): d 173.8 and
173.7 (C, OC55O), 157.8 and 157.9 (C, C-400), 144.4 and 144.0 (CH, C-30),
137.9 and 137.8 (C), 133.1 and 133.0 (C), 127.7 and 127.8 (2 C, CH, C-200
and 600), 121.8 and 121.9 (CH, C-4), 113.4 and 113.3 (2 C, CH, C-300 and
500), 112.6 (CH2, C-40), 59.6 (CH2, OCH2CH3), 55.6 and 55.7 (CH, C-2),
55.0 (CH3, OMe), 45.8 and 45.7 (C, C-20), 27.2 (CH2, C-3), 25.9 (CH3),
21.2 and 21.3 (CH3), 17.7 and 17.8 (CH3), 14.1 and 14.3 (CH3, OCH2CH3).
Mass: 316 (Mþ, 2%), 162 (14), 161 (100), 160 (4), 159 (4), 146 (5).
HRMS: m/z calcd. for C20H28O3Na (M þ Na): 339.1936. Found: 339.1938.
Further elution furnished starting material (26 mg).
3-[1-(4-Methoxyphenyl)ethyl]-6-methylhepta-1,5-diene (12): To a magne-
tically stirred solution of 20% KOH in methanol (3 ml) was added the ester 8
(55 mg, 0.17 mmol) and refluxed for 50 h. The reaction mixture was cooled,
taken in water (10 ml), and washed with CH2Cl2 (5 ml). The aqueous layer
was acidified with 3 N of HCl and extracted with CH2Cl2 (3 ꢁ 5 ml). The
organic extract was washed with brine and dried (Na2SO4). Evaporation of
the solvent furnished the acid 10 (50 mg, 99%). To a magnetically stirred
solution of the acid 10 (50 mg, 0.17 mmol) in dry benzene (2 ml) at 08C was
added oxalyl chloride (0.11 ml, 1.22 mmol) and stirred for 2 h at rt. Evapor-
ation of the solvent and excess oxalyl chloride under reduced pressure
afforded the acid chloride, which was taken in dry benzene (2 ml), added to
a magnetically stirred solution of 2-thiopyridine-1-oxide sodium salt
(39 mg, 0.26 mmol) and a catalytic amount of DMAP in dry benzene (3 ml),
and the resulting reaction mixture was refluxed for 1 h. To the ester 11 thus
formed was added dropwise a solution of tributyltin hydride and a catalytic
amount of AIBN in dry benzene (5 ml) over a period of 5 min and refluxed
for 14 h. The reaction mixture was cooled, washed with 1% ammonia
solution, and extracted with ether (3 ꢁ 5 ml). The combined ether extract
was washed with brine and dried (Na2SO4). Evaporation of the solvent and
purification of the residue over a silica-gel column using hexane as eluent
furnished a 3:2 diastereomeric mixture of the diene 12 (15 mg, 36%) as oil.
1
IR (neat): nmax/cm21 1511, 910. H NMR (300 MHz, CDCl3 þ CCl4, 3:2
mixture of the diastereomers): d 7.10–6.95 (2 H, m) and 6.85–6.72 (2 H,
m) [Ar-H], 5.43 (ddd, J 18.9, 10.2 and 8.4 Hz) and 5.57 (ddd, J 19.2, 9.9
and 9.0 Hz) [1 H, H-2], 5.11–4.80 (3 H, m, H-1 and 5), 3.77 (3 H, s,
OCH3), 2.56 (quintet, J 6.9 Hz) and 2.70 (d of q, J 6.9 and 5.7 Hz) [1 H],
2.20–1.60 (3 H, m), 1.64 and 1.68 (3 H, s), 1.42 and 1.53 (3 H, s)
[2 ꢁ olefinic CH3], 1.15 (d, J 7.5 Hz) and 1.23 (d, J 7.5 Hz) [3 H, sec-CH3].

Synthetic Approaches to Sporochnols A–C
1695
13C NMR (75 MHz, CDCl3 þ CCl4, 3:2 mixture of the diastereomers): d 157.8
(C, C-400), 140.4 and 141.2 (CH, C-2), 136.6 and 138.5 (C), 131.8 and 131.7
(C), 129.2 and 128.4 (2 C, CH, C-200 and 600), 123.1 and 122.8 (CH, C-5),
115.5 and 115.6 (CH2, C-1), 113.2 and 113.6 (2 C, CH, C-300 and 500), 55.1
(CH3, OMe), 50.9 and 51.7 (CH), 42.0 and 42.6 (CH), 30.7 and 31.4 (CH2),
25.9 (CH3), 19.3 and 19.9 (CH3), 17.9 and 18.0 (CH3). Mass: 244 (Mþ,
2%), 221 (3), 136 (10), 135 (100), 105 (9), 91 (7). HRMS: m/z calcd. for
C9H11O (M-C8H13): 135.0810. Found: 135.0815.
3-Methyl-3-(4-methoxyphenyl)pent-4-en-1-ol (17): To an ice-cold, magne-
tically stirred solution of the ester 4 (645 mg, 2.6 mmol) in dry ether (10 ml)
was added LAH (99 mg, 2.6 mmol) and stirred for 1 h. The reaction mixture
was then diluted with ether (20 ml) and carefully quenched with water
(5 ml). The organic layer was separated and the aqueous phase was
extracted with ether (15 ml). The combined organic phase was washed with
brine and dried (Na2SO4). Evaporation of the solvent and purification of the
residue over a silica-gel column using ethyl acetate–hexane (1:20 to 1:5) as
eluent furnished the alcohol 17 (494 mg, 92%). IR (neat): nmax/cm21 3370,
1
1634, 1609, 1580, 1513, 916. H NMR (300 MHz, CDCl3 þ CCl4): d 7.16
(2 H, d, J 8.7 Hz, H-20 and 60), 6.77 (2 H, d, J 8.7 Hz, H-30 and 50), 5.96 (1
H, dd, J 17.4 and 10.5 Hz, H-4), 5.06 (1 H, d, J 10.5 Hz) and 5.02 (1 H, d, J
17.4 Hz) [H-5], 3.74 (3 H, s, OCH3), 3.60–3.35 (2 H, m, H-1), 2.20–1.90
(3 H, m, H-2 and OH), 1.34 (3 H, s, tert-CH3). 13C NMR (75 MHz,
CDCl3 þ CCl4): d 157.7 (C, C-40), 146.9 (CH, C-4), 138.7 (C, C-10), 127.3
(2 C, CH, C-20 and 60), 113.5 (2 C, CH, C-30 and 50), 111.6 (CH2, C-5),
59.5 (CH2, C-1), 54.9 (CH3, OMe), 43.3 (CH2, C-2), 42.5 (C, C-3), 25.6
(CH3). Mass: m/z 206 (Mþ, 8%), 162 (12), 161 (100), 146 (11), 135 (9),
121 (9), 115 (10), 91 (20). HRMS: m/z calcd. for C13H18O2Na (M þ Na):
229.1204. Found: 229.1206.
3-(4-Methoxyphenyl)-3-methylpent-4-enal (16): To a magnetically stirred
solution of the primary alcohol 17 (404 mg, 2.0 mmol) in dry CH2Cl2 (3 ml)
was added a homogeneous mixture of PCC (1.3 g, 5.9 mmol) and silica gel
(1.3 g) and stirred vigorously for 30 min at RT. The reaction mixture was
then filtered through a small silica-gel column and the column was eluted
with excess CH2Cl2. Evaporation of the solvent and purification of the
residue over a silica-gel column using ethyl acetate–hexane (1:40 to 1:20) as
eluent furnished the pentenal 16 (352 mg, 88%) as an oil.[7] IR (neat):
1
nmax/cm21 2737, 1719, 1677, 1635, 1608, 1510, 920. H NMR (300 MHz,
CDCl3 þ CCl4): d 9.51 (1 H, t, J 3 Hz, CHO), 7.20 (2 H, d, J 8.7 Hz, H-20
and 60), 6.81 (2 H, d, J 8.7 Hz, H-30 and 50), 6.05 (1 H, dd, J 17.7 and
10.5 Hz, H-4), 5.16 (1 H, d, J 10.5 Hz) and 5.07 (1 H, d, J 17.7 Hz) [H-5],
3.76 (3 H, s, OCH3), 2.75 and 2.66 (2 H, d of AB q, J 15.0 and 3.0 Hz,
H-2), 1.48 (3 H, s, tert-CH3). 13C NMR (75 MHz, CDCl3 þ CCl4): d 201.7
(CH, CHO), 158.1 (C, C-40), 145.4 (CH, C-4), 137.2 (C, C-10), 127.3 (2 C,

1696
A. Srikrishna, G. Satyanarayana, and M. R. Prasad
CH, C-20 and 60), 113.8 (2 C, CH, C-30 and 50), 112.7 (CH2, C-5), 54.9 (CH3,
OMe), 53.3 (CH2, C-2), 42.2 (C, C-3), 26.3 (CH3).
4-(4-Methoxyphenyl)-4-methylhexa-1,5-dienyl methyl ether (18): To a
magnetically stirred suspension of methoxymethyltriphenylphosphonium
chloride (984 mg, 2.9 mmol) in dry THF (4 ml) at 08C was added a solution
n
of BuLi (1.95 M in hexane, 1.12 ml, 2.2 mmol) dropwise and the resulting
dark red solution was stirred for 15 min at rt. To a magnetcially stirred
solution of the aldehyde 16 (178 mg, 0.87 mmol) in dry THF (1 ml) at 08C
was added the dark-red-colored solution of methoxymethylenetriphenlypho-
sphorane and stirred for 40 min at rt. Saturated aq. NH4Cl solution (5 ml)
was added to the reaction mixture and extracted with ether (2 ꢁ 10 ml). The
combined ether extract was washed with brine and dried (Na2SO4). Evapor-
ation of the solvent and purification of the residue over a silica-gel column
using hexane as eluent furnished the enol ether 18 (141 mg, 70%) as oil. IR
(neat): nmax/cm21 1664, 1654, 1609, 1511, 915. 1H NMR (300 MHz,
CDCl3 þ CCl4, 5:4 mixture of E,Z-isomers): d 7.21 and 7.19 (2 H, d, J
9.0 Hz, H-20 and 60), 6.79 and 6.80 (2 H, d, J 9.0, Hz, H-30 and 50), 6.20
(d, J 12.9 Hz) and 5.84 (m of d, J 6.0 Hz) [1 H, H-1], 6.00 (dd, J 17.4 and
10.8 Hz) and 5.99 (dd, J 17.4 and 10.8 Hz) [1 H, H-6], 5.13–4.80 (2 H, m,
H-6), 4.45 (t of d, J 12.9 and 7.8 Hz) and 4.15 (quintet, J 6.9 Hz) [1 H,
H-2], 3.77 and 3.76 (3 H, s), 3.53 and 3.40 (3 H, s), 2.50 (d of AB q J 12.9
and 7.5 Hz) and 2.32 (1 H, dd, J 7.5 and 2.7 Hz) [H-3], 1.32 and 1.30 (3 H,
13
s, tert-CH3). C NMR (75 MHz, CDCl3 þ CCl4): d 157.6 (C, C-40), 148.6
and 147.2 (CH), 147.0 (CH), 139.2 and 139.1 (C, C-10), 127.7 and 127.6
(2 C, CH, C-20 and 60), 113.3 and 113.2 (2 C, CH, C-30 and 50), 111.7
and 111.6 (CH2, C-6), 103.1 and 98.7 (CH, C-2), 59.3 and 55.7 (CH3,
OCH3), 55.0 (CH3, ArOMe), 43.8 (C), 39.6 and 35.1 (CH2, C-3), 25.3 and
24.9 (CH3).
4-(4-Methoxyphenyl)-4-methylhex-5-enal (19): A solution of the enol ether
18 (141 mg, 0.6 mmol) in THF (3 ml) and 3 N of HCl (3 ml) was magnetically
stirred for 1.5 h at rt. The reaction mixture was diluted with water (5 ml) and
extracted with ether (3 ꢁ 7 ml). The combined ether extract was washed with
aqueous NaHCO3 and brine, and dried (Na2SO4). Evaporation of the solvent
and purification of residue over a silica-gel column using ethyl acetate–
hexane (1:49 to 1:20) as eluent furnished the aldehyde 19 (115 mg, 87%) as
1
oil. IR (neat): nmax/cm21 2721, 1723, 1634, 1609, 1580, 1512, 917. H
NMR (300 MHz, CDCl3 þ CCl4): d 9.67 (1 H, s, CHO), 7.18 (2 H, d,
J 8.7 Hz, H-20 and 60), 6.81 (2 H, d, J 8.7 Hz, H-30 and 50), 5.96 (1 H, dd, J
17.1 and 10.5 Hz, H-5), 5.11 (1 H, d, J 10.5 Hz) and 5.04 (1 H, d, J
17.1 Hz) [H-6], 3.77 (3 H, s, OCH3), 2.40–2.19 (2 H, m, H-2), 2.19–1.70
(2 H, m, H-3), 1.34 (3 H, s, tert-CH3). 13C NMR (75 MHz, CDCl3 þ CCl4):
d 201.6 (CH, CHO), 157.9 (C, C-40), 146.2 (CH, C-5), 138.0 (C, C-10),

Synthetic Approaches to Sporochnols A–C
1697
127.5 (2 C, CH, C-20 and 60), 113.6 (2 C, CH, C-30 and 50), 112.3 (CH2, C-6),
55.0 (CH3, OMe), 43.0 (C, C-4), 39.9 (CH2), 32.5 (CH2), 25.1 (CH3).
3-(4-Methoxyphenyl)-3,7-dimethylocta-1,6-diene (methyl ether of sporo-
chnol A 9): To a cold (08C), magnetically stirred suspension of isopropyltri-
phenylphosphonium bromide (420 mg, 1.1 mmol) in dry THF (3 ml) was
n
added a solution of BuLi (1.9 M in hexane, 0.41 ml, 0.78 mmol) dropwise
and the resulting red-colored solution was stirred for 15 min at rt. The isopro-
pylidene-triphenylphosphorane thus formed was added to a magnetically
stirred solution of the aldehyde 19 (34 mg, 0.15 mmol) in THF (1 ml) and
the reaction mixture was stirred for 1 h at rt. Saturated aq. ammonia
solution (3 ml) was added to the reaction mixture and extracted with ether
(3 ꢁ 5 ml). The combined ether extract was washed with brine and dried
(Na2SO4). Evaporation of the solvent and purification of residue over
silver nitrate–impregnated silica-gel column using hexane as eluent
furnished the diene 9 (30 mg, 77%) as oil. IR (neat): nmax/cm21 3081,
1
1633, 1609, 1580, 1512, 913. H NMR (300 MHz, CDCl3 þ CCl4): d 7.18
(2 H, d, J 8.7 Hz, H-20 and 60), 6.78 (2 H, d, J 8.7 Hz, H-30 and 50), 5.98
(1 H, dd, J 17.4 and 10.8 Hz, H-2), 5.05–5.00 (1 H, m), 5.04 (1 H, d, J
10.8 Hz) and 4.99 (1H, d, J 17.4 Hz) [H-1], 3.77 (3 H, s, OCH3), 2.00–
1.50 (4 H, m), 1.64 (3 H, s) and 1.50 (3 H, s) [2 ꢁ olefinic-CH3], 1.34 (3
13
H, s, tert-CH3). C NMR (75 MHz, CDCl3 þ CCl4): d 157.6 (C, C-40),
147.3 (CH, C-2), 139.3 (C, C-7), 131.0 (C, C-10), 127.6 (2 C, CH, C-20
and 60), 125.0 (CH, C-6), 113.4 (2 C, CH, C-30 and 50), 111.5 (CH2, C-1),
55.0 (CH3, OMe), 43.7 (C, C-3), 41.3 (CH2, C-4), 25.8 (CH3), 25.3 (CH3),
23.4 (CH2, C-5), 17.7 (CH3). Mass: 244 (Mþ, 5%), 162 (20), 161 (100),
146 (8), 134 (8), 121 (9), 91 (11).
ACKNOWLEDGMENTS
We thank the C. S. I. R., New Delhi, India, for the award of a research fellow-
ship to GS, and Indian Institute of Science for providing Young Science
Fellowship of IISc to MRP.
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