Synthesis of the analogues of lurlenic acid with modification in the side-chain or in the aromatic nucleus: Summary of the structure-activity relationships

Article abstract of DOI:10.1002/(SICI)1099-0690(199801)1998:1<43::AID-EJOC43>3.0.CO;2-L

Nine analogues of lurlenic acid [(4E,8E,12E)-14-[2′-hydroxy3′,4′-dimethyl-5′-(1″- β-D-xylopyranosyloxy)phenyl]-4,8,12-trimethyltetradeca-4,8,12-trienoic acid (1)], a component of the mating pheromone of the green flagellate Chlamydomonas allensworthii, we

Full text of DOI:10.1002/(SICI)1099-0690(199801)1998:1<43::AID-EJOC43>3.0.CO;2-L

FULL PAPER
Pheromone Synthesis, CLXXXVII[᭛]
Synthesis of the Analogues of Lurlenic Acid with Modification in the
Side-Chain or in the Aromatic Nucleus: Summary of the Structure؊Activity
Relationships
Shin-ichi Takanashi and Kenji Mori*
Department of Chemistry, Faculty of Science, Science University of Tokyo,
Kagurazaka 1-3, Shinjuku-ku, Tokyo 162, Japan
Fax: (internat.) ϩ 81-3-3235-2214
Received July 21, 1997
Keywords: Chlamydomonas / Glycosides / Lurlenic acid / Pheromones / Sex attractant / Structure-activity relationships
Nine analogues of lurlenic acid {(4E,8E,12E)-14-[2Ј-hydroxy-
3Ј,4Ј-dimethyl-5Ј-(1Љ-β- -xylopyranosyloxy)phenyl]-4,8,12- the 2Ј-deoxy-2Ј-methyl analogue 10. Structural requirements
trimethyltetradeca-4,8,12-trienoic acid (1)}, a component of for the expression of the pheromonal activity is briefly discus-
the mating pheromone of the green flagellate Chlamydomo- sed, indicating the importance of the sugar part, the phenolic
nate (7), butyl lurlenate (8), the bisdemethyl analogue 9, and
D
nas allensworthii, were synthesized. They are the (12Z) iso-
mer 2, the hexahydro derivative 3, the norprenyl analogue 4,
the homoprenyl analogue 5, methyl lurlenate (6), ethyl lurle-
hydroxy group, the appropriate length and the unsaturation
of the side-chain part, and the presence of a polar group at
the terminal position of the side-chain.
Lurlenic acid (1) (Scheme 1) is a component of the sex Scheme 1. Structures of lurlenic acid (1) and its analogues
pheromone excreted by the female gametes of the green
flagellate Chlamydomonas allensworthii to attract the male
gametes for mating[1][2][3]. It is attractive to the male ga-
metes at a concentration as low as 10Ϫ12 [1]. The structure
1 proposed for lurlenic acid[2] was confirmed by our syn-
thesis[4]. Compound 1 consists of three parts: the sugar, the
aromatic nucleus, and the isoprenoidal side-chain. We
therefore started our project to modify these three parts one
by one so as to clarify the structureϪactivity relationships.
The first phase of our endeavor to modify the sugar part
revealed only the -xyloside 1 to be extremely bioactive,
indicating the importance of the sugar in pheromone per-
ception by the male gametes[5]. This paper describes the
modification of other two parts, and reports the synthesis
of the seven analogues 2Ϫ8 with a modified side-chain, and
the two analogues 9 and 10 with a modified aromatic nu-
cleus. The present work confirms the importance of all of
the three parts of 1 for the expression of its pheromone ac-
tivity.
(12Z) Isomer 2 of Lurlenic Acid
In our first synthesis of lurlenic acid[4][6], what we ob-
tained as the final product was a 2:1 mixture of lurlenic
acid (1) and its (12Z) isomer 2. Its bioassay against the male
thesis[4][7], we secured pure lurlenic acid (1) with its bioac-
gametes of Chlamydomonas allensworthii showed it to be
tivity equal to the natural product. We therefore became
almost as active as 1 itself. Then in the second syn-
interested in preparing the pure (12Z) isomer 2 of 1 so as
to evaluate its bioactivity exactly.
Scheme 2 summarizes the synthesis of 2. The (12Z)
double bond of 2 was constructed by Still’s (Z)-selective
[᭛] Part CLXXXVI: H. Takikawa, S. Sano, K. Mori, Liebigs Ann.
1997, 2495Ϫ2498.
Eur. J. Org. Chem. 1998, 43Ϫ55
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1434Ϫ193X/98/0101Ϫ0043 $ 17.50ϩ.50/0
43

S. Takanashi, K. Mori
FULL PAPER
Scheme 2. Synthesis of the (12Z) isomer 2 of lurlenic acid
verted to the corresponding chloride 15. The dianion de-
rived from the known C12 building block 17, which was
prepared from farnesol (16)[4], was alkylated with 15 to give
the new phenylsulfone 18. Reductive removal of the phenyl-
sulfonyl group of 18 was achieved with lithium triethylhy-
droborate in the presence of palladium chloride 1,3-bis(di-
phenylphosphanyl)propane [(dppp)PdCl2] complex in
THF[10] to give 19. This alcohol 19 was converted to the
(12Z) isomer 2 of lurlenic acid via 20Ϫ25 by the sequence
of reactions used in our previous synthesis of lurlenic acid
1
(1)[4]. In the H-NMR spectrum of 2, the proton signals of
the methyl group at C-12 (17-H3) appeared at δ ϭ 1.76 as
a singlet confirming the (12Z) geometry of 2. The overall
yield of 2 was 4.0% based on 3,4-dimethyl-p-hydroquinone
(11, 18 steps), or 5.3% based on farnesol (16, 16 steps).
A bioassay revealed 2 to be approximately 0.1% as active
as 1. Since all the intermediates as well as 2 itself are non-
crystalline and cannot be purified rigorously by recrystalli-
zation, a possibility cannot be excluded that 2 contains
0.1% of lurlenic acid (1) while 2 is totally inactive. The
seemingly full activity of the previously synthesized 2:1 mix-
ture of 1 and 2[4] manifests the difficulty of discerning the
full activity from 66% activity by the bioassay method em-
ployed.
Scheme 3. Synthesis of hexahydrolurlenic acid (3)
Reagents: (a) (CF3CH2O)2P(O)CH(Me)CO2Et, 18-crown-6 MeCN
complex, KN(TMS)2, THF (81%). Ϫ (b) LiAlH4, Et2O (85%). Ϫ
(c) MsCl, LiCl, sym-collidine, DMF (94%). Ϫ (d) 2 equiv. BuLi,
HMPA, THF, 15 (85%). Ϫ (e) 0.1 equiv. (dppp)PdCl2, 3 equiv.
LiBEt3H, THF (89%). Ϫ (f) DessϪMartin periodinane, C5H5N,
CH2Cl2. Ϫ (g) 1) NaClO2, NaH2PO4, DMSO/H2O/MeCN; 2)
CH2N2, Et2O (75% based on 19). Ϫ (h) 9 equiv. CsF, HMPA . Ϫ
(i) Ac2O, C5H5N (80% based on 21). Ϫ (j) TsOH, MeOH (92%). Ϫ
(k) 3 equiv. 2,3,4-tri-O-acetyl-α--xylopyranosyl fluoride, 3 equiv.
1,1,3,3-tetramethylguanidine, 8 equiv. BF3 ·OEt2, MeCN. Ϫ (l)
NaOH, MeOH, H2O (54% based on 24).
modification[8][9] of the HornerϪWadsworthϪEmmons re-
action. The starting aldehyde 12 was prepared from 2,3-
dimethyl-p-hydroquinone (11) according to the published
method[4]. Reaction of 12 with ethyl 2-[bis(2,2,2-trifluoro-
ethyl)phosphono]propanoate in the presence of potassium
hexamethyldisilazide [KN(TMS)2] and 18-crown-6 in THF
furnished the (Z)-unsaturated ester 13 as the single isomer
as revealed by its H-NMR analysis [δ ϭ 1.90, d, J ϭ 1
Hz, 3 H, CHϭC(Me)CO2Et]. Reduction of 13 with lithium
tetrahydridoaluminate gave the alcohol 14, which was con- NaOH, MeOH, H2O (55% based on 33).
Reagents: (a) 0.05 equiv. (dba)2Pd, 3 equiv. LiCl, DMF (98%). Ϫ
(b) 9 equiv. CsF, HMPA . Ϫ (c) Ac2O, C5H5N (82% based on 29).
Ϫ (d) TsOH, MeOH (95%). Ϫ (e) H2, PtO2, EtOH (quant.). Ϫ
(f) 3 equiv. 2,3,4-tri-O-acetyl-α--xylopyranosyl fluoride, 3 equiv.
1,1,3,3-tetramethylguanidine, 8 equiv. BF3 ·OEt2, MeCN. Ϫ (g)
1
44 Liebigs Ann./Recueil 1997, 43Ϫ55

Pheromone Synthesis, CLXXXVII
FULL PAPER
Scheme 4. Synthesis of norprenyl analogue 4 of lurlenic acid
Reagents: (a) 0.025 equiv. (dba)3Pd2, 3 equiv. LiCl, DMF (83%). Ϫ (b) 9 equiv. CsF, HMPA . Ϫ (c) Ac2O, C5H5N (74% based on 36).
Ϫ (d) TsOH, MeOH (97%). Ϫ (e) 3 equiv. 2,3,4-tri-O-acetyl-α--xylopyranosyl fluoride, 3 equiv. 1,1,3,3-tetramethylguanidine, 8 equiv.
BF3 ·OEt2, MeCN. Ϫ (f) NaOH, MeOH, H2O (42% based on 39).
Additional Three Analogues 3, 4 and 5 with a Modified
Side-Chain
higher prenylogue 5 was as active as lurlenic acid against
the male gametes of Chlamydomonas allensworthii.
To further clarify the structural requirement at the side-
chain part for the expression of bioactivity, three analogues
3, 4 and 5 of lurlenic acid were synthesized.
Scheme 5. Synthesis of homoprenyl analogue 5 of lurlenic acid
Hexahydrolurlenic acid (3) was synthesized as shown in
Scheme 3. By the methods previously reported[4], geranyl-
geraniol (26) and 2,3-dimethyl-p-hydroquinone (11) were
converted to the acetoxy ester 27 and the stannane 28,
respectively. These two building blocks were coupled in the
presence of bis(dibenzylideneacetone)palladium [(dba)2Pd],
and further transformation of the protective groups of the
coupling product 29 yielded 32 via 30 and 31[4]. Hydrogen-
ation of 32 over Adams’ platinum oxide afforded the hexa-
hydroaglycone part 33 as a stereoisomeric mixture. Glycos-
idation of 33 with 2,3,4-tri-O-acetyl-α--xylopyranosyl flu-
oride by Yamaguchi’s method[11] afforded 34, whose depro-
tection provided hexahydrolurlenic acid (3). This derivative
3 was biologically inactive.
The next target was the lower prenylogue 4 (Scheme 4).
The necessary and known intermediate 35[12] was prepared
from farnesol (16) by the method used for the preparation
of its higher prenylogue 27[4]. The coupling of the stannane
28 with 35 afforded 36, which was converted to 39 via 37
and 38. Glycosidation of 39 was followed by removal of
the protective groups of 40 to give the lower prenylogue 4
(norprenyllurlenic acid). This acid 4 was a 1.3:1 mixture of
(8E) and (8Z) isomer, and weakly bioactive (0.1% as active
as lurlenic acid).
Reagents: (a) LiAlH4, Et2O (95%). Ϫ (b) DessϪMartin periodi-
nane, C5H5N, CH2Cl2 (90%). Ϫ (c) 2-lithiopropene, THF (89%).
Ϫ (d) MeC(OEt)3, EtCO2H (83%). Ϫ (e) 9 equiv. CsF, HMPA . Ϫ
(f) Ac2O, C5H5N (90% based on 44). Ϫ (g) TsOH, MeOH (quant.).
Ϫ (h) 3 equiv. 2,3,4-tri-O-acetyl-α--xylopyranosyl fluoride, 3
equiv. 1,1,3,3-tetramethylguanidine, 8 equiv. BF3 ·OEt2, MeCN. Ϫ
(i) NaOH, MeOH, H2O (47% based on 47).
Scheme 5 summarizes the synthesis of the higher pre-
nylogue 5. The known protected aglycone 29 of lurlenic acid
was reduced with lithium tetrahydridoaluminate to give the
Ester Derivatives 6, 7 and 8 of Lurlenic Acid
It is known that lurlenol [the alcohol (CH2OH instead of
corresponding primary alcohol 41. This was oxidized with CO2H of 1) corresponding to lurlenic acid] is another nat-
DessϪMartin periodinane[13] to give the aldehyde 42. Treat- urally occurring pheromone component of Chlamydomonas
ment of 42 with 2-lithiopropene yielded the allyic alcohol allensworthii[3], and our synthetic lurlenol is also highly bio-
43, which was subjected to the Johnson orthoester Claisen active[4]. It is of interest to clarify whether the esters of lurl-
rearrangement[14] to give 44 with clean stereoselectivity at enic acid (1) are bioactive or not. To solve this problem, we
C-4 to give (4E)-44. Conversion of 44 to 47 was carried out synthesized three esters 6, 7 and 8 of a mixture of 1 and its
in the usual manner[4] via 45 and 46, and 47 was glycosy- (12Z) isomer obtained by the palladium-catalyzed coup-
lated to give 48. Removal of the protective groups of 48 ling route[4]
furnished the higher prenylogue 5 (homoprenyllurlenic As shown in Scheme 6, lurlenic acid was methylated with
acid) as a 1.3:1 mixture of (16E) and (16Z) isomers. This diazomethane to give amorphous methyl lurlenate (6) as a
.
Liebigs Ann./Recueil 1997, 43Ϫ55
45

S. Takanashi, K. Mori
Scheme 7. Synthesis of 3Ј,4Ј-bisdemethyllurlenic acid (9)
FULL PAPER
1.5:1 mixture of its (12E) and (12Z) isomers. It was as bi-
oactive as lurlenic acid itself. Secondly, the known methyl
lurlenate tetraacetate (49)[4] was prepared from 32 by glyco-
sidation, and treated with sodium ethoxide in ethanol to
effect transesterification, yielding amorphous ethyl lurlenate
(7) as a 1.3:1 mixture of (12E) and (12Z) isomers. Ethyl
lurlenate (7) was 0.1% as bioactive as lurlenic acid. Thirdly,
treatment of 49 with sodium butoxide in 1-butanol afforded
butyl lurlenate (8), which was obtained as an amorphous
solid consisting of 1.3:1 ratio of (12E) and (12Z) isomers
contaminated with about 10% of an unknown purity. This
butyl ester (8) was weakly bioactive to show 0.1% bioactiv-
ity of 1.
Scheme 6. Synthesis of ester 6, 7 and 8 of lurlenic acid
Reagents: (a) 1.2 equiv. DHP, TsOH, THF. Ϫ (b) 1.5 equiv. SEMCl,
(iPr)2NEt, CH2Cl2 (44% based on 50). Ϫ (c) 1.5 equiv. BuLi, 1.5
equiv. Me3SnCl, THF (quant.). Ϫ (d) 0.025 equiv. (dba)3Pd2, 3
equiv. LiCl, DMF (92%). Ϫ (e) 9 equiv. CsF, HMPA. Ϫ (f) Ac2O,
C5H5N (77% based on 54). Ϫ (g) TsOH, MeOH (88%). Ϫ (h) 3
equiv. 2,3,4-tri-O-acetyl-α--xylopyranosyl fluoride,
3 equiv.
1,1,3,3-tetramethylguanidine, 8 equiv. BF3 ·OEt2, MeCN. Ϫ (i)
NaOH, MeOH, H2O (44% based on 57).
groups of 62 yielded 2Ј-deoxy-2Ј-methyllurlenic acid (10) as
a 1.5:1 mixture of (12E) and (12Z) isomers. A bioassay of
10 proved it to be biologically inactive.
Scheme 8. Synthesis of 2Ј-deoxy-2Ј-methyllurlenic acid (10)
Reagents: (a) CH2N2, MeOH (99%). Ϫ (b) 3 equiv. 2,3,4-tri-O-
acetyl-α--xylopyranosyl fluoride, 3 equiv. 1,1,3,3-tetramethylgua-
nidine, 8 equiv. BF3 ·OEt2, MeCN. Ϫ (c) EtONa, EtOH (53% ba-
sed on 32). Ϫ (d) BuONa, BuOH (46% based on 32).
Analogues 9 and 10 with a Modified Aromatic Nucleus
Scheme 7 summarizes the synthesis of 3Ј,4Ј-didemeth-
yllurlenic acid (9), which is necessary to evaluate the role of
the two methyl groups attached to the aromatic nucleus.
Commercially available bromohydroquinone (50) was pro-
tected twice to give 52 via 51. Lithiation of 52 was followed
by stannylation with trimethylstannyl chloride to furnish
53. Palladium-catalyzed coupling of 53 with 27 gave 54.
Transformation of protective groups of 54 via 55 and 56
yielded 57. Glycosylation of 57 to 58 was followed by the
removal of its protective groups to give 3Ј,4Ј-bisdemethyl-
lurlenic acid (9) as a 1.3:1 mixture of (12E) and (12Z) iso-
mers. This analogue 9 was weakly bioactive (0.1% activity
of 1).
Reagents: (a) Tf2O, C5H5N. Ϫ (b) Me4Sn, LiCl, (Ph3P)2PdCl2,
DMF. Ϫ (c) TsOH, MeOH (63% based on 30). Ϫ (d) 3 equiv. 2,3,4-
tri-O-acetyl-α--xylopyranosyl fluoride, 3 equiv. 1,1,3,3-tetrame-
thylguanidine, 8 equiv. BF3 ·OEt2, MeCN. Ϫ (e) NaOH, MeOH,
H2O (51% based on 61).
Brief Summary of the Pheromone Structure؊Activity
Relationships
Although the full details of the pheromone structure-ac-
Finally, the phenolic hydroxy group at C-2Ј of lurlenic tivity relationship will be discussed separately by Jaenicke
acid was replaced by a methyl group to give 10 (Scheme 8). et al. in due course, Scheme 9 summarizes the results of
For that purpose, the known intermediate 30 was converted bioassay of lurlenic acid (1) and related compounds so far
to the triflate 59. Treatment of 59 with tetramethylstannane synthesized.
and bis(triphenylphosphane)palladium chloride complex in
Fully bioactive compounds are lurlenic acid (1), lurlenol,
DMF[15] afforded 60. Removal of the tetrahydropyranyl homoprenyllurlenic acid (5) and methyl lurlenate (6), while
(THP) protective group of 60 furnished 61, which was gly- the totally inactive compounds are the possible precursor
cosylated to give 62. Further removal of the protective of 1 derived from Plastoquinone 4, glycosides other than β-
46
Liebigs Ann./Recueil 1997, 43Ϫ55

Pheromone Synthesis, CLXXXVII
FULL PAPER
Scheme 9. Pheromone structure-activity relationships
Bruker DPX 300 (75.5 MHz), (CDCl3 at δC ϭ 77.0 or CD3OD at
δC ϭ 49.0 as an internal standard). Ϫ MS: Jeol JMS-SX 102A.
Ϫ Optical rotation: Jasco DIP-1000. Ϫ Column chromatography:
Merck Kieselgel 60 Art 1.07734 and Merck Kieselgel 60 Art
1.15111. Ϫ TLC: 0.25 mm Merck silica gel plates (60F-254).
-xylopyranoside and α- or β--arabinopyranoside, hexa-
hydrolurlenic acid (3), and 2Ј-deoxy-2Ј-methyllurlenic acid
(10). Those which show a bioactivity of 0.1% of that of
active 1 are its (12Z) isomer 2, norprenyllurlenic acid (4),
ethyl and butyl lurlenate (6 and 7), and 3Ј,4Ј-bisdemethyl-
lurlenic acid (9).
Accordingly, the important structural features for the ex-
pression of bioactivity are : (i) the sugar part, (ii) the phe-
nolic hydroxy group, (iii) the appropriate length and the
unsaturation of the side-chain part, and (iv) the presence of
Ethyl (Z)-2-Methyl-4-{3Ј,4Ј-dimethyl-5Ј-tetrahydropyranyloxy-
2Ј-[2-(trimethylsilyl)ethoxymethoxy]phenyl}-2-butenoate (13): To a
stirred solution of ethyl 2-[bis(2,2,2-trifluoroethyl)phosphono]pro-
panoate (4.52 g, 13.0 mmol) and 18-crown-6 acetonitrile complex
(19.8 g, 64.9 mmol) in THF (100 ml), potassium bis(trimethylsilyl)-
a polar group such as a carboxy, a hydroxymethyl or an amide (0.6  in toluene, 21.7 ml, 13.0 mmol) was added dropwise
at Ϫ78°C under argon. Then the aldehyde 12 (3.42 g, 8.66 mmol)
was added and the resulting mixture was stirred for 30 min at
Ϫ78°C. After the addition of water (100 ml), the mixture was ex-
tracted three times with diethyl ether (200 ml). The combined eth-
ereal extracts were successively washed with water and brine, dried
with Na2SO4 and concentrated in vacuo. The residue was purified
by chromatography on silica gel (150 g, hexane/ethyl acetate, 30:1)
to give 3.36 g (81%) of 13 as a colorless oil; n2D2 ϭ 1.5064. Ϫ IR
(film): ν˜max ϭ 1715 cmϪ1 (s, CϭO), 1640 (w, CϭC), 1585 (w, Cϭ
C), 1250 (m, SiϪC), 1220 (s, CϪO), 1200 (m, CϪO), 1125 (s,
CϪO), 1080 (m, CϪO), 1065 (m, CϪO), 1040 (m, CϪO). Ϫ 1H
NMR (300 MHz, CDCl3): δ ϭ 0.02 (s, 9 H, SiMe3), 0.99 (br. t, J ϭ
9 Hz, 2 H, CH2Si), 1.32 (t, J ϭ 7 Hz, 3 H, CH3CH2), 1.50Ϫ2.10 (m,
6 H, THP), 1.90 [d, J ϭ 1 Hz, 3 H, CHϭC(Me)CO2Et], 2.16 (s, 3
H, ArCH3), 2.21 (s, 3 H, ArCH3), 3.55Ϫ3.65 (m, 1 H, THP),
ester group at the terminal position of the side-chain.
We thank Prof. L. Jaenicke (Universität Köln) for bioassays and
stimulating discussions. Our thanks are also due to Prof. R. C.
Starr (University of Texas) for discussions. Geranylgeraniol and
farnesol were supplied by Kuraray Co., to whom we express our
thanks. Financial support of this work by a Grant-in-Aid for Scien-
tific Research (No. 09680576), Japanese Ministry of Education, Sci-
ence, Sports and Culture is gratefully acknowledged. This work was
also supported by Kyowa Hakko Kogyo Co., Takasago International
Corporation, T. Hasegawa Co., and Mitsubishi Chemical Co.
Experimental Section
General: Melting points: Uncorrected values. Ϫ IR: Perkin-
Elmer 1640. Ϫ 1H NMR: Jeol JNM-EX 90A (90 MHz) and Bruker 3.80Ϫ4.00 (m, 5 H, THP, ArCH2, CH2CH2Si), 4.23 (q, J ϭ 7 Hz,
DPX 300 (300 MHz), (TMS at δH ϭ 0.00, CHCl3 at δH ϭ 7.26 or
2 H, CH3CH2), 4.91 (s, 2 H, OCH2O), 5.30 (t, J ϭ 3 Hz, 1 H,
CHD2OD at δH ϭ 3.31 as an internal standard). Ϫ 13C NMR: THP), 6.08 (dt, J ϭ 1 Hz, JЈ ϭ 7 Hz, 1 H, olefinic H), 6.80 (s, 1
Liebigs Ann./Recueil 1997, 43Ϫ55
47

S. Takanashi, K. Mori
FULL PAPER
H, aromatic H). Ϫ C26H42O6 (428.7): calcd. C 65.24, H 8.84; found
C 64.90, H 8.48.
on silica gel (100 g, hexane/ethyl acetate, 3:1) to give 2.71 g (85%)
of 18 as a colorless oil; n2D2 ϭ 1.5250. Ϫ IR (film): ν˜max ϭ 3445
cmϪ1 (m, OϪH), 1650 (m, CϭC), 1305 (s, SO2), 1250 (m, SiϪC),
1145 (s, SO2), 1085 (s, CϪO), 1065 (s, CϪO), 1035 (m, CϪO). Ϫ
1H NMR (300 MHz, CDCl3): δ ϭ 0.03 (s, 9 H, SiMe3), 1.00 (t,
J ϭ 9 Hz, 2 H, CH2Si), 1.10 (s, 3 H, 17-H3), 1.50Ϫ1.75 (m, 5 H,
THP, 2-H2), 1.56 (s, 3 H, 15-H3), 1.62 (s, 3 H, 16-H3), 1.75Ϫ2.10
(m, 8 H, OH, THP, 6,7-H2), 2.01 (t, J ϭ 8 Hz, 2 H, 3-H2), 2.14 (s,
3 H, ArCH3), 2.19 (s, 3 H, ArCH3), 2.62 (ddd, J ϭ 3 Hz, JЈ ϭ 14
Hz, JЉ ϭ 14 Hz, 1 H, 11-H), 2.89 (dd, J ϭ 3 Hz, JЈ ϭ 14 Hz, 1 H,
11-H), 3.15Ϫ3.45 (m, 2 H , 14-H2), 3.50Ϫ3.62 (m, 1 H, THP), 3.58
(t, J ϭ 8 Hz, 2 H, 1-H2), 3.80Ϫ3.95 (m, 2 H, THP, 10-H), 3.85 (br.
t, J ϭ 9 Hz, 2 H, CH2CH2Si), 4.91 (d, J ϭ 1 Hz, 2 H, OCH2O),
4.95Ϫ5.10 (m, 2 H, 5,9-H), 5.29 (br. d, J ϭ 2 Hz, 1 H, THP), 5.40
(t, J ϭ 6 Hz, 1 H, 13-H), 6.72 (s, 1 H, aromatic H), 7.50 (dt, J ϭ
1 Hz, JЈ ϭ 11 Hz, 2 H, aromatic H), 7.60 (dt, J ϭ 1 Hz, JЈ ϭ 11
Hz, 1 H, aromatic H), 7.86 (dd, J ϭ 1 Hz, JЈ ϭ 11 Hz, 2 H,
aromatic H). Ϫ 13C NMR (75.5 MHz, CDCl3): δ ϭ Ϫ1.5, 12.3,
13.6, 15.8, 16.1, 18.2, 19.1, 23.6, 23.7, 25.3, 25.9, 29.1, 29.6, 30.6,
30.7, 35.8, 39.5, 62.1, 62.5, 63.5, 67.3, 96.8, 96.9, 97.9, 113.6, 117.0,
123.7, 125.1, 127.3, 128.6, 129.2, 130.6, 130.7, 131.0, 131.3, 133.3,
135.1, 137.9, 145.1, 148.3, 151.2, 151.3. Ϫ HRMS: C42H64O7SSi
[Mϩ]: calcd. 740.4142, found 740.4160. This compound so strongly
retained the solvents that the correct combustion analytical data
could not be obtained.
(Z)-4-{3Ј,4Ј-Dimethyl-5Ј-tetrahydropyranyloxy-2Ј-[2-(trimethyl-
silyl)ethoxymethoxy]phenyl}-2-methyl-2-buten-1-ol (14): To
a
stirred suspension of lithium tetrahydroaluminate (238 mg, 6.26
mmol) in diethyl ether (20 ml) was added a solution of 13 (3.00 g,
6.26 mmol) in diethyl ether (40 ml) at 0°C. After stirring for 1 h at
0°C, water (0.25 ml), 15% NaOH (0.25 ml) and water (0.75 ml)
were added to the reaction mixture with ice-cooling. The mixture
was filtered through a Celite pad and washed with diethyl ether.
The ethereal solution was dried with Na2SO4, and concentrated in
vacuo. The residue was purified by chromatography on silica gel
(75 g, hexane/ethyl acetate, 10:1) to give 2.31 g (85%) of 14 as a
colorless oil; nD23 ϭ 1.5093. Ϫ IR (film): ν˜max ϭ 3440 cmϪ1 (m,
OϪH), 1585 (w, CϭC), 1250 (m, SiϪC), 1220 (m, CϪO), 1125 (s,
CϪO), 1080 (s, CϪO), 1065 (s, CϪO). Ϫ 1H NMR (300 MHz,
CDCl3): δ ϭ 0.03 (s, 9 H, SiMe3), 1.01 (t, J ϭ 9 Hz, 2 H, CH2Si),
1.52Ϫ1.75 (m, 3 H, THP), 1.81 [s, 3 H, CHϭC(Me)CH2],
1.82Ϫ2.27 (m, 4 H, THP, OH), 2.15 (s, 3 H, ArCH3), 2.20 (s, 3 H,
ArCH3), 3.39 (br. d, J ϭ 10 Hz, 2 H, ArCH2), 3.53Ϫ3.63 (m, 1 H,
THP), 3.80Ϫ3.95 (m, 1 H, THP), 3.87 (t, J ϭ 9 Hz, 2 H,
CH2CH2Si), 4.18 (d, J ϭ 5 Hz, 2 H, CH2OH), 4.91 (s, 2 H,
OCH2O), 5.33 (t, J ϭ 3 Hz, 1 H, THP), 5.39 (t, J ϭ 3 Hz, olefinic
H), 6.79 (s, 1 H, aromatic H). Ϫ HRMS: C24H40O5Si [Mϩ]: calcd.
436.2640, found 436.2642. Due to the instability of 14, the correct
combustion analytical data could not be obtained.
(4E,8E,12Z)-14-{3Ј,4Ј-Dimethyl-5Ј-tetrahydropyranyloxy-2Ј-[2-
(trimethylsilyl)ethoxymethoxy]phenyl}-4,8,12-trimethyltetradeca-
4,8,12-trien-1-ol (19): To a stirred solution of 18 (2.50 g, 3.37 mmol)
and [1,3-bis(diphenylphosphanyl)propane]palladium chloride com-
plex (199 mg, 0.337 mmol) in dry THF (45 ml) was added dropwise
lithium triethylhydroborate (1.0  in THF, 10.1 ml, 10.1 mmol) at
0°C under argon. The stirring was continued for 3 h at 4°C. Then
the mixture was diluted with 10% NaCN aqueous solution (50 ml)
and extracted three times with diethyl ether (100 ml). The com-
bined ethereal extracts were successively washed with water and
brine, dried with Na2SO4, and concentrated in vacuo. The residue
was purified by chromatography on silica gel (75 g, hexane/ethyl
(Z)-4-{3Ј,4Ј-Dimethyl-5Ј-tetrahydropyranyloxy-2Ј-[2-(trimethyl-
silyl)ethoxymethoxy]phenyl}-2-methyl-2-butenyl Chloride (15): To a
solution of 14 (2.05 g, 4.69 mmol) in DMF (40 ml) were added
lithium chloride (595 mg, 14.1 mmol) and sym-collidine (2.27 g,
18.8 mmol) at 0°C. The mixture was stirred for 30 min at 0°C to
dissolve lithium chloride and then methanesulfonyl chloride (1.08
g, 9.40 mmol) was added. After stirring for 1 h at 0°C, the reaction
mixture was diluted with water (100 ml) and extracted three times
with diethyl ether (100 ml). The combined ethereal extracts were
washed with water and brine, dried with Na2SO4, and concentrated
in vacuo. The residue was purified by chromatography on silica gel
(70 g, hexane/ethyl acetate, 25:1) to give 2.01 g (94%) of 15 as a
colorless oil; IR (film): ν˜max ϭ 1585 cmϪ1 (w, CϭC), 1250 (m,
SiϪC), 1200 (m, CϪO), 1125 (s, CϪO), 1080 (s, CϪO), 1065 (s,
acetate, 10:1) to give 1.81 g (89%) of 19 as a colorless oil; nD22
ϭ
1.5079. Ϫ IR (film): ν˜max ϭ 3420 cmϪ1 (m, OϪH), 1250 (m, SiϪC),
1200 (m, CϪO), 1125 (m, CϪO), 1080 (m, CϪO), 1065 (m, CϪO).
1
Ϫ H NMR (300 MHz, CDCl3) δ ϭ 0.04 (s, 9 H, SiMe3), 1.01 (br.
1
CϪO). Ϫ H NMR (90 MHz, CDCl3): δ ϭ 0.03 (s, 9 H, SiMe3),
t, J ϭ 8 Hz, 2 H, CH2Si), 1.50Ϫ1.80 (m, 5 H, THP, 2-H2), 1.61 (s,
6 H, 15,16-H3), 1.74 (d, J ϭ 1 Hz, 3 H, 17-H3), 1.80Ϫ1.92 (m, 2
H, THP), 1.92Ϫ2.25 (m, 12 H, OH, THP, 3,6,7,10,11-H2), 2.16 (s,
3 H, ArCH3), 2.21 (s, 3 H, ArCH3), 3.28Ϫ3.45 (m, 2 H, 14-H2),
3.53Ϫ3.65 (m, 1 H, THP), 3.60 (t, J ϭ 7 Hz, 2 H, 1-H2), 3.85Ϫ4.00
(m, 1 H, THP), 3.87 (br. t, J ϭ 8 Hz, 2 H, CH2CH2Si), 4.91 (s, 2
H, OCH2O), 5.12Ϫ5.22 (m, 2 H, 5,9-H), 5.25Ϫ5.37 (m, 2 H, THP,
13-H), 6.77 (s, 1 H, aromatic H). Ϫ 13C NMR (75.5 MHz, CDCl3):
δ ϭ Ϫ1.5, 12.3, 13.6, 15.8, 15.9, 18.2, 19.1, 23.4, 25.3, 26.4, 26.5,
28.7, 30.6, 30.7, 32.1, 35.8, 35.9, 39.6, 62.1, 62.7, 62.9, 67.3, 96.9,
97.8, 113.5, 123.7, 124.3, 124.6, 124.9, 125.8, 130.8, 132.1, 134.5,
134.9, 136.0, 148.2, 151.3. This product was contaminated with
about 5% of an inseparable impurity and therefore was used for
the next reaction without further purification. The impurity disap-
peared after further operation at the steps to convert 19 to 21. The
NMR signals (in italics) are due to the impurity.
1.01 (br. t, J ϭ 9 Hz, 2 H, CH2Si), 1.45Ϫ2.30 (m, 6 H, THP), 1.85
[d, J ϭ 1 Hz, 3 H, CHϭC(Me)CH2], 2.15 (s, 3 H, ArCH3), 2.20 (s,
3 H, ArCH3), 3.42 (d, J ϭ 8 Hz, 2 H, ArCH2), 3.55Ϫ4.10 (m, 2
H, THP), 3.87 (br. t, J ϭ 9 Hz, 2 H, CH2CH2Si), 4.18 (s, 2 H,
CH2Cl), 4.91 (s, 2 H, OCH2O), 5.25 (t, J ϭ 3 Hz, 1 H, THP), 5.54
(dt, J ϭ 1 Hz, JЈ ϭ 8 Hz, 1 H, olefinic H), 6.78 (s, 1 H, aromatic
H). This compound was used for the next reaction without
further purification.
(4E,8E,12Z)-14-{3Ј,4Ј-Dimethyl-5Ј-tetrahydropyranyloxy-2Ј-[2-
(trimethylsilyl)ethoxymethoxy]phenyl}-4,8,12-trimethyl-10-
(phenylsulfonyl)tetradeca-4,8,12-trien-1-ol (18): To a stirred solu-
tion of 17 (1.66 g, 5.16 mmol) in THF (20 ml) and HMPA (7 ml)
was added dropwise butyllithium (1.58  in hexane, 6.53 ml, 10.3
mmol) at Ϫ50°C under argon, and the mixture was stirred at
Ϫ50°C for 30 min. Then a solution of 15 (1.95 g, 4.29 mmol) in
THF (15 ml) was added dropwise, and the stirring was continued
Methyl (4E,8E,12Z)-14-{3Ј,4Ј-Dimethyl-5Ј-tetrahydropyranyl-
for 20 h at 4°C. After the addition of water (100 ml), the mixture oxy-2Ј-[2-(trimethylsilyl)ethoxymethoxy]phenyl}-4,8,12-trimethyl-
was neutralized with acetic acid and extracted three times with di- tetradeca-4,8,12-trienoate (21): To a stirred solution of Dess-Martin
ethyl ether (100 ml). The combined ethereal extracts were succes- periodinane (3.59 g, 8.49 mmol) in dichloromethane (60 ml) was
sively washed with water and brine, dried with Na2SO4, and con- added pyridine (3.36 g, 42.5 mmol) under argon. The stirring was
centrated in vacuo. The residue was purified by chromatography continued at room temperature until a clear solution was obtained
48
Liebigs Ann./Recueil 1997, 43Ϫ55

Pheromone Synthesis, CLXXXVII
FULL PAPER
and a solution of 19 (1.70 g, 2.83 mmol) in dichloromethane (10
5 H, OH, 5,9,13-H, THP), 6.75 (s, 1 H, aromatic H). This com-
ml) was added. The mixture was stirred at room temperature for 1 pound was used for the next reaction without further purification.
h, diluted with a saturated NaHCO3 solution (25 ml) and a satu-
Methyl
(4E,8E,12Z)-14-(2Ј-Acetoxy-3Ј,4Ј-dimethyl-5Ј-tetra-
rated Na2S2O3 solution (25 ml), and extracted three times with di-
chloromethane (50 ml). The combined extracts were successively
washed with water and brine, dried with Na2SO4, and filtered
through silica gel. The filtrate was concentrated in vacuo to give
1.47 g of crude 20. Ϫ IR (film): ν˜max ϭ 2715 cmϪ1 (m, CHO), 1725
(s, CϭO), 1580 (w, CϭC), 1250 (m, SiϪC), 1200 (m, CϪO), 1125
hydropyranyloxyphenyl)-4,8,12-trimethyltetradeca-4,8,12-trienoate
(23): To a stirred and ice-cooled solution of crude 22 (948 mg) in
dry pyridine (5.0 ml) was added acetic anhydride (500 mg, 4.90
mmol). The stirring was continued for 20 h at room temperature
and for another 1 h after the addition of water (50 ml). The mixture
was extracted three times with diethyl ether (50 ml). The combined
ethereal extracts were successively washed with water, a saturated
CuSO4 solution, a saturated NaHCO3 solution and brine, dried
with Na2SO4, and concentrated in vacuo. The residue was purified
by chromatography on silica gel (50 g, hexane/ethyl acetate, 10:1)
1
(s, CϪO), 1080 (s, CϪO), 1065 (s, CϪO), 1035 (m, CϪO). Ϫ H
NMR (90 MHz, CDCl3): δ ϭ 0.03 (s, 9 H, SiMe3), 1.01 (br. t, J ϭ
9 Hz, 2 H, CH2Si), 1.40Ϫ2.50 (m, 18 H, THP, 2,3,6,7,10,11-H2),
1.60 (s, 6 H, 15,16-H3), 1.73 (br. s, 3 H, 17-H3), 2.16 (s, 3 H,
ArCH3), 2.21 (s, 3 H, ArCH3), 3.33 (d, J ϭ 6 Hz, 2 H, 14-H2),
3.45Ϫ4.00 (m, 2 H, THP), 3.93 (br. t, J ϭ 9 Hz, 2 H, CH2CH2Si),
4.92 (s, 2 H, OCH2O), 5.00Ϫ5.40 (m, 4 H, 5,9,13-H, THP), 6.78
(s, 1 H, aromatic H), 9.75 (t, J ϭ 2 Hz, 1 H, CHO). Ϫ To a solution
of crude 20 (1.47 g) in dimethyl sulfoxide (20 ml) and acetonitrile
(20 ml) was added a solution of potassium dihydrogen phosphate
(1.32 g, 8.46 mmol) in water (24 ml). The mixture was stirred at
room temperature for 10 min and sodium chlorite (512 mg, 5.66
mmol) was added. After stirring for 2 h at room temperature, the
mixture was diluted with brine (70 ml) and extracted three times
with diethyl ether (100 ml). The combined ethereal extracts were
washed with brine, dried with Na2SO4, and concentrated in vacuo.
The residue was dissolved in diethyl ether (10 ml) and treated with
a solution of diazomethane (8.49 mmol) in diethyl ether (10 ml) at
0°C. The mixture was stirred at room temperature for 1 h and
concentrated in vacuo. The residue was purified by chromatogra-
phy on silica gel (50 g, hexane/ethyl acetate, 50:1) to give 1.33 g
(75% based on 19) of 21 as a yellowish oil; n2D3 ϭ 1.5095. Ϫ IR
(film): ν˜max ϭ 1740 cmϪ1 (s, CϭO), 1585 (w, CϭC), 1250 (s, SiϪC),
1200 (s, CϪO), 1150 (s, CϪO), 1125 (s, CϪO), 1080 (s, CϪO), 1065
(s, CϪO), 1035 (s, CϪO). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ
0.03 (s, 9 H, SiMe3), 1.00 (t, J ϭ 9 Hz, 2 H, CH2Si), 1.52Ϫ1.80
(m, 3 H, THP), 1.60 (s, 6 H, 15,16-H3), 1.73 (d, J ϭ 1 Hz, 3 H,
17-H3), 1.80Ϫ1.90 (m, 2 H, THP), 1.90Ϫ2.22 (m, 9 H, THP,
6,7,10,11-H2), 2.15 (s, 3 H, ArCH3), 2.20 (s, 3 H, ArCH3), 2.28 (t,
J ϭ 9 Hz, 2 H, 3-H2), 2.40 (br. t, J ϭ 9 Hz, 2 H, 2-H2), 3.25Ϫ3.45
(m, 2 H, 14-H2), 3.50Ϫ3.65 (m, 1 H, THP), 3.65 (s, 3 H, CO2CH3),
3.80Ϫ4.00 (m, 1 H, THP), 3.86 (t, J ϭ 9 Hz, 2 H, CH2CH2Si),
4.91 (s, 2 H, OCH2O), 5.10Ϫ5.20 (m, 2 H, 5.9-H), 5.25Ϫ5.35 (m,
2 H, THP, 13-H), 6.78 (s, 1 H, aromatic H). Ϫ 13C NMR (75.5
MHz, CDCl3): δ ϭ Ϫ1.5, 12.3, 13.6, 15.86, 15.95, 18.2, 19.1, 23.5,
25.3, 26.5, 26.6, 28.7, 30.6, 32.1, 33.0, 34.6, 39.5, 51.4, 62.1, 67.2,
96.9, 97.8, 113.5, 123.7, 124.2, 124.9, 125.1, 130.8, 132.1, 133.2,
135.0, 136.0, 148.2, 151.3, 173.9. Ϫ C37H60O6Si (629.0): calcd. C
70.66, H 9.62; found C 70.28, H 9.38
to give 615 mg (80% based on 21) of 23 as a colorless oil; nD23
ϭ
1.5161. Ϫ IR (film): ν˜max ϭ 1760 cmϪ1 (s, CϭO), 1740 (s, CϭO),
1585 (w, CϭC), 1200 (s, CϪO), 1195 (s, CϪO), 1125 (s, CϪO),
1080 (s, CϪO), 1035 (s, CϪO). Ϫ 1H NMR (300 MHz, CDCl3):
δ ϭ 1.55Ϫ1.80 (m, 3 H, THP), 1.60 (s, 6 H, 15,16-H3), 1.72 (d, J ϭ
1 Hz, 3 H, 17-H3), 1.80Ϫ1.90 (m, 2 H, THP), 1.90Ϫ2.20 (m, 9 H,
THP, 6,7,10,11-H2), 2.03 (s, 3 H, ArCH3), 2.16 (s, 3 H, ArCH3),
2.24Ϫ2.34 (m, 2 H, 3-H2), 2.29 (s, 3 H, acetyl), 2.41 (br. t, J ϭ 9
Hz, 2 H, 2-H2), 3.15 (d, J ϭ 7 Hz, 2 H, 14-H2), 3.52Ϫ3.62 (m, 1
H, THP), 3.66 (s, 3 H, CO2CH3), 3.90 (ddd, J ϭ 2 Hz, JЈ ϭ 12
Hz, JЉ ϭ 12 Hz, 1 H, THP), 5.14 (br. t, J ϭ 6 Hz, 2 H, 5,9-H),
5.21 (dt, J ϭ 1 Hz, JЈ ϭ 7 Hz, 1 H, 13-H), 5.32 (t, J ϭ 3 Hz, 1 H,
THP), 6.83 (s, 1 H, aromatic H). Ϫ C33H48O6 (540.7): calcd. C
73.30, H 8.95; found C 72.95, H 8.60.
Methyl
(4E,8E,12Z)-14-(2Ј-Acetoxy-5Ј-hydroxy-3Ј,4Ј-dimeth-
ylphenyl)-4,8,12-trimethyltetradeca-4,8,12-trienoate (24): To a
stirred solution of 23 (550 mg, 1.02 mmol) in methanol (5 ml) was
added p-toluenesulfonic acid monohydrate (10 mg, 0.058 mmol).
The stirring was continued for 4 h at room temperature. Then the
mixture was quenched with a saturated NaHCO3 solution (50 ml)
and extracted three times with diethyl ether (50 ml). The combined
ethereal extracts were washed with water and brine, dried with
MgSO4, and concentrated in vacuo. The residue was purified by
chromatography on silica gel (50 g, hexane/ethyl acetate, 10:1) to
give 431 mg (92%) of 24 as a yellowish oil; n2D3 ϭ 1.5170. Ϫ IR
(film): ν˜max ϭ 3445 cmϪ1 (m, OϪH), 1760 (s, CϭO), 1740 (s, Cϭ
O), 1590 (w, CϭC), 1190 (s, CϪO), 1080 (s, CϪO). Ϫ 1H NMR
(300 MHz, CDCl3): δ ϭ 1.60 (s, 6 H, 15,16-H3), 1.72 (d, J ϭ 1 Hz,
3 H, 17-H3), 1.95Ϫ2.20 (m, 8 H, 6,7,10,11-H2), 2.02 (s, 3 H,
ArCH3), 2.11 (s, 3 H, ArCH3), 2.25Ϫ2.35 (m, 2 H, 3-H2), 2.31 (s,
3 H, acetyl), 2.42 (br. t, J ϭ 8 Hz, 2 H, 2-H2), 3.11 (d, J ϭ 8 Hz,
2 H, 14-H2), 3.67 (s, 3 H, CO2CH3), 5.02Ϫ5.17 (m, 2 H, 5,9-H),
5.21 (dt, J ϭ 1 Hz, JЈ ϭ 6 Hz, 1 H, 13-H), 5.58 (s, 1 H, OH), 6.48
(s, 1 H, aromatic H). Ϫ 13C NMR (75.5 MHz, CDCl3): δ ϭ 11.9,
13.1, 15.8, 20.5, 23.4, 26.3, 26.4, 28.5, 31.9, 33.0, 34.6, 39.4, 51.6,
113.4, 121.6, 122.4, 124.1, 125.1, 125.8, 129.8, 130.9, 133.1, 135.0,
136.5, 140.8, 151.6, 169.8, 174.3. Ϫ C28H40O5 (456.6): calcd. C
73.65, H 8.83; found C 73.32, H 8.97.
Methyl (4E,8E,12Z)-14-(2Ј-Hydroxy-3Ј,4Ј-dimethyl-5Ј-tetrahy-
dropyranyloxyphenyl)-4,8,12-trimethyltetradeca-4,8,12-trienoate
(22): To a stirred solution of 21 (900 mg 1.43 mmol) in HMPA (9
ml) was added cesium fluoride (1.74 g, 11.4 mmol) under argon.
The stirring was continued for 2 h at 120°C. Then the mixture was
Methyl (4E,8E,12Z)-14-[2Ј-Acetoxy-3Ј,4Ј-dimethyl-5Ј-(2Љ,3Љ,4Љ-
tri-O-acetyl-1Љ-β--xylopyranosyloxy)phenyl]-4,8,12-trimethyl-
diluted with diethyl ether (200 ml), and the solution was washed tetradeca-4,8,12-trienoate (25): To a stirred solution of 24 (350 mg,
with water and brine. The ethereal solution was dried with Na2SO4 0.743 mmol), 2,3,4-tri-O-acetyl-α--xylopyranosyl fluoride (620
and concentrated in vacuo to give 948 mg of crude 22 as a brown mg, 2.23 mmol) and 1,1,3,3-tetramethylguanidine (513 mg, 4.46
oil. Ϫ IR (film): ν˜max ϭ 3480 cmϪ1 (m, OϪH), 1740 (s, CϭO),
mmol) in dry acetonitrile (8 ml) was added boron trifluorideϪdi-
1200 (s, CϪO), 1120 (s, CϪO), 1080 (s, CϪO), 1035 (s, CϪO). Ϫ ethyl ether (844 mg, 5.94 mmol) at room temperature under argon.
1H NMR (90 MHz, CDCl3):
1.40Ϫ2.45 (m, 18 H, After stirring at room temperature for 20 h, The mixture was
δ
ϭ
2,3,6,7,10,11-H2, THP), 1.60 (s, 6 H, 15,16-H3), 1.77 (s, 3 H, 17-
H3), 2.17 (s, 6 H, ArCH3), 3.31 (d, J ϭ 9 Hz, 2 H, 14-H2),
quenched with a saturated NaHCO3 solution (20 ml) and extracted
three times with diethyl ether (50 ml). The combined ethereal ex-
3.50Ϫ4.10 (m, 2 H, THP), 3.65 (s, 3 H, CO2CH3), 4.90Ϫ5.40 (m, tracts were successively washed with water and brine, dried with
Liebigs Ann./Recueil 1997, 43Ϫ55 49

S. Takanashi, K. Mori
FULL PAPER
Na2SO4, and concentrated in vacuo. The residue was purified by
14-[2Ј-Hydroxy-3Ј,4Ј-dimethyl-5Ј-(1Љ-β--xylopyranosyloxy)-
chromatography on silica gel (50 g, hexane/ethyl acetate, 3:1) to phenyl]-4,8,12-trimethyltetradecanoic Acid (3): This was prepared
give 413 mg of crude 25 as a colorless oil. Ϫ IR (film): ν˜max ϭ 1755
from crude 34 (345 mg) in the same manner as described for 2 to
give 159 mg (55% based on 33) of 3 as a colorless waxy solid. Ϫ
cmϪ1 (s, CϭO), 1585 (w, CϭC), 1245, (s, CϪO), 1220 (s, CϪO),
1195 (s, CϪO), 1080 (s, CϪO), 1060 (m, CϪO), 1040 (s, CϪO). [α]2D4 ϭ Ϫ16 (c ϭ 0.10, MeOH). Ϫ Rf ϭ 0.65 (iBuOH/MeOH/H2O,
This was employed in the next step without further purification.
8:1:1). Ϫ IR (film): ν˜max ϭ 3370 cmϪ1 (s, OϪH), 2925 (s), 2860 (s),
1710 (m, CϭO), 1550 (w), 1460 (m), 1455 (m), 1415 (m), 1380 (w),
1225 (m, CϪO), 1075 (m, CϪO), 1050 (s, CϪO), 1030 (s, CϪO).
(4E,8E,12Z)-14-[2Ј-Hydroxy-3Ј,4Ј-dimethyl-5Ј-(1Љ-β--xylopy-
ranosyloxy)phenyl]-4,8,12-trimethyltetradeca-4,8,12-trienoic Acid
(2): To a solution of crude 25 (413 mg) in methanol (3.0 ml) was
added a 10% NaOH aqueous solution (3.0 ml). The stirring was
continued for 2 h at room temperature. The mixture was neu-
tralized with acetic acid, and extracted three times with chloroform
(50 ml). The combined extracts were dried with Na2SO4, and con-
centrated in vacuo. The residue was purified by chromatography
on silica gel (25 g, chloroform/methanol, 10:1) to give 213 mg (54%
based on 24) of 2 as a colorless amorphous solid. Ϫ [α]2D4 ϭ Ϫ15
1
Ϫ H NMR (300 MHz, CD3OD): δ ϭ 0.86 (d, J ϭ 6 Hz, 3 H, 15
or 16-H3), 0.88 (d, J ϭ 6 Hz, 3 H, 15 or 16-H3), 0.94 (d, J ϭ 6 Hz,
3 H, 17-H3), 1.00Ϫ1.75 (m, 19 H, 3,5,6,7,9,10,11,13-H2, 4,8,12-H),
2.14 (s, 3 H, 18 or 19-H3), 2.16 (s, 3 H, 18 or 19-H3), 2.20Ϫ2.35
(m, 2 H, 2-H2), 2.45Ϫ2.70 (m, 2 H, 14-H2), 3.22 (t, J ϭ 10 Hz, 1
H, 5Љa-H), 3.41 (t, J ϭ 8 Hz, 1 H, 3Љ-H), 3.46 (t, J ϭ 8 Hz, 1 H,
2Љ-H), 3.57 (ddd, J ϭ 5 Hz, JЈ ϭ 8 Hz, JЉ ϭ 10 Hz, 1 H, 4Љ-H),
3.89 (dd, J ϭ 5 Hz, JЈ ϭ 10 Hz, 1 H, 5Љe-H), 4.64 (d, J ϭ 8 Hz, 1
H, 1Љ-H), 6.71 (s, 1 H, 6Ј-H). Ϫ 13C NMR (75.5 MHz, CD3OD):
δ ϭ 12.8, 13.0, 19.7, 19.8, 20.12, 20.19, 20.24, 25.4, 29.1, 33.37,
33.46, 33.53, 33.61, 33.68, 33.74, 33.9, 38.2, 38.4, 38.5, 66.8, 71.0,
74.9, 77.8, 105.2, 105.3, 117.1, 126.1, 126.5, 126.6, 129.2, 129.3,
148.9, 150.4, 150.5, 179.6. Ϫ MS (70 eV); m/z (%): 538 (1) [Mϩ],
520 (1), 478 (1), 420 (28), 406 (43), 388 (42), 151 (100). Ϫ HRMS:
C30H50O8 [Mϩ]: calcd. 538.3506, found 538.3499.
(c ϭ 0.15, MeOH). Ϫ Rf ϭ 0.65 (iBuOH/MeOH/H2O, 8:1:1) (ref[4]
R ϭ 0.65). Ϫ IR (KBr): ν
ϭ 3395 cmϪ1 (s, OϪH), 2965 (m),
.
˜
f
max
2930 (m), 2900 (m), 2865 (m), 1715 (m, CϭO), 1560 (w, CϭC),
1480 (m), 1440 (m), 1385 (w), 1280 (m, CϪO), 1215 (s, CϪO), 1165
(s, CϪO), 1100 (m, CϪO), 1065 (s, CϪO), 1055 (s, CϪO), 1005
1
(m), 985 (m), 845 (m). Ϫ H NMR (300 MHz, CD3OD): δ ϭ 1.60
(s, 6 H, 15,16-H3), 1.76 (s, 3 H, 17-H3), 1.90Ϫ2.00 (m, 2 H, 6-H2),
2.00Ϫ2.25 (m, 6 H, 7,10,11-H2), 2.14 (s, 3 H, 18 or 19-H3), 2.16 (s,
3 H, 18 or 19-H3), 2.25 (br. t, J ϭ 7 Hz, 2 H, 3-H2), 2.35 (br. t,
J ϭ 7 Hz, 2 H, 2-H2), 3.19 (t, J ϭ 10 Hz, 1 H, 5Љa-H), 3.20Ϫ3.30
(m, 2 H, 14-H2), 3.38 (t, J ϭ 7 Hz, 1 H, 3Љ-H), 3.42 (t, J ϭ 7 Hz,
1 H, 2Љ-H), 3.56 (ddd, J ϭ 5 Hz, JЈ ϭ 7 Hz, JЉ ϭ 10 Hz, 1 H, 4Љ-
H), 3.86 (dd, J ϭ 5 Hz, JЈ ϭ 10 Hz, 1 H, 5Љe-H), 4.60 (d, J ϭ 7
Hz, 1 H, 1Љ-H), 5.15 (br. s, 2 H, 5,9-H), 5.33 (t, J ϭ 7 Hz, 1 H, 13-
H), 6.72 (s, 1 H, 6Ј-H). Ϫ 13C NMR (75.5 MHz, CD3OD): δ ϭ
12.7, 12.9, 16.07, 16.13, 23.8, 27.6, 29.5, 32.9, 34.6, 36.0, 40.7, 66.9,
71.1, 74.9, 77.9, 105.1, 116.5, 124.4, 125.4, 125.9, 126.1, 126.5,
127.3, 127.9, 134.8, 136.1, 137.4, 148.9, 150.6, 178.6. Ϫ MS (70
eV); m/z (%): 532 (1) [Mϩ], 514 (3), 496 (1), 472 (1), 400 (73), 189
(74), 151 (100), 81 (33). Ϫ HRMS: C30H42O7 [Mϩ Ϫ H2O]: calcd.
514.2930, found 514.2933.
Methyl (4E)-10-{3Ј,4Ј-Dimethyl-5Ј-tetrahydropyranyloxy-2Ј-[2-
(trimethylsilyl)ethoxymethoxy]phenyl}-4,8-dimethyldeca-4,8-
dienoate (36): To a stirred solution of 28 (3.58 g, 6.96 mmol) and
35 (1.50 g, 5.60 mmol) in DMF (30 ml) were added lithium chloride
(885 mg, 20.9 mmol) and tris(benzylideneacetone)dipalladium(0)
(159 mg, 0.174 mmol) under argon. The stirring was continued for
7 h at 100°C. Then the mixture was diluted with water (50 ml)
and extracted three times with diethyl ether (50 ml). The combined
ethereal extracts were successively washed with water and brine,
dried with Na2SO4, and concentrated in vacuo. The residue was
purified by chromatography on silica gel (100 g, hexane/ethyl ace-
tate, 20:1) to give 2.63 g (84%) of 36 as a yellowish oil; nD23
ϭ
1.5058. Ϫ IR (film): ν˜max ϭ 1740 cmϪ1 (s, CϭO), 1580 (w, CϭC),
1250 (m, SiϪC), 1200 (m, CϪO), 1155 (m, CϪO), 1125 (m, CϪO),
1080 (m, CϪO), 1065 (m, CϪO), 1035 (m, CϪO). Ϫ 1H NMR (90
MHz, CDCl3): δ ϭ 0.03 (s, 9 H, SiMe3), 1.01 (t, J ϭ 9 Hz, 2 H,
CH2Si), 1.50Ϫ2.25 (m, 10 H, 6,7-H2, THP), 1.60 (s, 3 H, 11-H3),
1.70 (s, 3 H, 12-H3), 2.16 (s, 3 H, ArCH3), 2.21 (s, 3 H, ArCH3),
2.25Ϫ2.45 (m, 4 H, 2,3-H2), 3.35 (d, J ϭ 7 Hz, 2 H, 10-H2),
3.45Ϫ4.10 (m, 2 H, THP), 3.64 (s, 3 H, CO2CH3), 3.86 (t, J ϭ 9
Hz, 2 H, CH2CH2Si), 4.92 (s, 2 H, OCH2O), 5.00Ϫ5.40 (m, 3 H,
5,9-H, THP), 6.79 (s, 1 H, aromatic H). Ϫ C32H52O6Si (560.8):
calcd. C 68.53, H 9.35; found C 68.69, H 9.38.
Methyl 14-(2Ј-Acetoxy-5Ј-hydroxy-3Ј,4Ј-dimethylphenyl)-4,8,12-
trimethyltetradecanoate (33): To a stirred solution of 32 (300 mg,
0.656 mmol) in ethanol (6 ml) was added platinum oxide (60.0 mg,
0.264 mmol) under hydrogen. The stirring was continued for 24 h
at room temperature. Then the mixture was filtered through a Ce-
lite pad and washed with diethyl ether. The ethereal solution was
concentrated in vacuo. The residue was purified by chromatogra-
phy on silica gel (30 g, hexane/ethyl acetate, 10:1) to give 310 mg
(quantitative) of 33 as a colorless oil; n2D2 ϭ 1.4928. Ϫ IR (film):
ν˜max ϭ 3445 cmϪ1 (m, OϪH), 1760 (s, CϭO), 1730 (s, CϭO), 1590
Methyl
(4E)-10-(2Ј-Hydroxy-3Ј,4Ј-dimethyl-5Ј-tetrahydropy-
1
(w, CϭC), 1195 (s, CϪO), 1080 (s, CϪO). Ϫ H NMR (300 MHz,
ranyloxyphenyl)-4,8-dimethyldeca-4,8-dienoate (37): This was pre-
pared from 36 (1.95 g, 3.48 mmol) in the same manner as described
for 22 to give 2.30 g of crude 37 as a brown oil. Ϫ IR (film): ν˜max ϭ
3415 cmϪ1 (m, OϪH), 1740 (s, CϭO), 1200, (s, CϪO), 1170 (s,
CϪO), 1125 (s, CϪO), 1075 (s, CϪO), 1035 (s, CϪO). Ϫ 1H NMR
(90 MHz, CDCl3): δ ϭ 1.50Ϫ2.25 (m, 10 H, 6,7-H2, THP), 1.60 (s,
3 H, 11-H3), 1.77 (s, 3 H, 12-H3), 2.17 (s, 6 H, ArCH3), 2.15Ϫ2.45
(m, 4 H, 2,3-H2), 3.29 (d, J ϭ 7 Hz, 2 H, 10-H2), 3.40Ϫ4.20 (m, 2
H, THP), 3.64 (s, 3 H, CO2CH3), 4.90Ϫ5.40 (m, 4 H, 5,9-H, THP,
OH), 6.74 (s, 1 H, aromatic H). This was employed in the next step
without further purification.
CDCl3): δ ϭ 0.84 (d, J ϭ 6 Hz, 3 H, 15 or 16-H3), 0.87 (d, J ϭ 6
Hz, 3 H, 15 or 16-H3), 0.91 (d, J ϭ 6 Hz, 3 H, 17-H3), 1.00Ϫ1.75
(m, 19 H, 3,5,6,7,9,10,11,13-H2, 4,8,12-H), 2.03 (s, 3 H, ArCH3),
2.11 (s, 3 H, ArCH3), 2.20Ϫ2.45 (m, 4 H, 2,14-H2), 2.33 (s, 3 H,
acetyl), 3.67 (s, 3 H, CO2CH3), 5.15Ϫ5.30 (m, 1 H, OH), 6.47 (s, 1
H, aromatic H). Ϫ C28H46O5 (462.7): calcd. C 72.69, H 10.02;
found C 72.48, H 10.03.
Methyl 14-[2Ј-Acetoxy-3Ј,4Ј-dimethyl-5Ј-(2Љ,3Љ,4Љ-tri-O-acetyl-
1Љ-β--xylopyranosyloxy)phenyl]-4,8,12-trimethyltetradecanoate
(34): This was prepared from 33 (250 mg, 0.540 mmol) in the same
manner as described for 25 to give 345 mg of crude 34 as a colorless
oil. Ϫ IR (film): ν˜max ϭ 1760 cmϪ1 (s, CϭO), 1580 (w, CϭC), 1245,
Methyl
(4E)-10-(2Ј-Acetoxy-3Ј,4Ј-dimethyl-5Ј-tetrahydropy-
(s, CϪO), 1220 (s, CϪO), 1195 (s, CϪO), 1120 (m, CϪO), 1080 (s, ranyloxyphenyl)-4,8-dimethyldeca-4,8-dienoate (38): This was pre-
CϪO), 1060 (s, CϪO), 1040 (s, CϪO). This was employed in the
next step without further purification.
pared from crude 37 (2.30 g) in the same manner as described for
23 to give 1.21 g (74% based on 36) of 38 as a yellowish oil; nD23
ϭ
50
Liebigs Ann./Recueil 1997, 43Ϫ55

Pheromone Synthesis, CLXXXVII
FULL PAPER
1.5148. Ϫ IR (film): ν˜max ϭ 1760 cmϪ1 (s, CϭO), 1740 (s, CϭO),
(4E,8E)-14-{3Ј,4Ј-Dimethyl-5Ј-tetrahydropyranyloxy-2Ј-[2-
1585 (w, CϭC), 1220 (s, CϪO), 1195 (s, CϪO), 1125 (s, CϪO), (trimethylsilyl)ethoxymethoxy]phenyl}-4,8,12-trimethyltetradeca-
1080 (s, CϪO), 1035 (s, CϪO). Ϫ 1H NMR (90 MHz, CDCl3): δ ϭ 4,8,12-trien-1-ol (41): This was prepared from 29 (3.30 g, 5.25
1.50Ϫ2.25 (m, 10 H, 6,7-H2, THP), 1.60 (s, 3 H, 11-H3), 1.65 [s, mmol) in the same manner as described for 14 to give 3.00 g (95%)
5/3 H, 12-H3 (E)], 1.70 [br. s, 4/3 H, 12-H3 (Z)], 2.03 (s, 3 H,
ArCH3), 2.17 (s, 3 H, ArCH3), 2.25Ϫ2.45 (m, 4 H, 2,3-H2), 2.30
of 41 as a colorless oil; n2D4 ϭ 1.5150. Ϫ IR (film): ν˜max ϭ 3435
cmϪ1 (m, OϪH), 1250 (m, SiϪC), 1200 (m, CϪO), 1150 (m, CϪO),
(s, 3 H, acetyl), 3.17 (d, J ϭ 7 Hz, 2 H, 10-H2), 3.40Ϫ4.20 (m, 2 1125 (s, CϪO), 1080 (s, CϪO), 1065 (s, CϪO), 1035 (s, CϪO). Ϫ
H, THP), 3.64 (s, 3 H, CO2CH3), 5.00Ϫ5.25 (m, 2 H, 5,9-H), 5.32 1H NMR (90 MHz, CDCl3): δ ϭ 0.05 (s, 9 H, SiMe3), 1.01 (t, J ϭ
(br. s, 1 H, THP), 6.82 (s, 1 H, aromatic H). Ϫ C28H40O6 (472.6): 9 Hz, 2 H, CH2Si), 1.40Ϫ2.20 (m, 19 H, THP, 2,3,6,7,10,11-H2,
calcd. C 71.16, H 8.53; found C 70.78, H 8.62.
OH), 1.60 (s, 6 H, 15,16-H3), 1.70 (s, 3 H, 17-H3), 2.15 (s, 3 H,
ArCH3), 2.21 (s, 3 H, ArCH3), 3.35 (d, J ϭ 7 Hz, 2 H, 14-H2),
3.40Ϫ4.10 (m, 2 H, THP), 3.60 (t, J ϭ 6 Hz, 2 H, 1-H2), 3.85 (t,
J ϭ 9 Hz, 2 H, CH2CH2Si), 4.92 (s, 2 H, OCH2O), 5.00Ϫ5.40 (m,
4 H, 5,9,13-H, THP), 6.78 (s, 1 H, aromatic H). These spectral data
are identical to those reported in ref[4], and very similar to those
of 19.
Methyl (4E)-10-(2Ј-Acetoxy-5Ј-hydroxy-3Ј,4Ј-dimethylphenyl)-
4,8-dimethyldeca-4,8-dienoate (39): This was prepared from 38 (950
mg, 2.01 mmol) in the same manner as described for 24 to give 753
mg (97%) of 39 as a yellowish oil; n2D2 ϭ 1.5171. Ϫ IR (film): νmax ϭ
˜
3445 cmϪ1 (s, OϪH), 1760 (s, CϭO), 1735 (s, CϭO), 1590 (m, Cϭ
C), 1245 (s, CϪO), 1215 (s, CϪO), 1200 (s, CϪO), 1080 (s, CϪO).
1
Ϫ H NMR (300 MHz, CDCl3): δ ϭ 1.61 (s, 3 H, 11-H3), 1.65 [s,
(4E,8E)-14-{3Ј,4Ј-Dimethyl-5Ј-tetrahydropyranyloxy-2Ј-[2-
(trimethylsilyl)ethoxymethoxy]phenyl}-4,8,12-trimethyltetradeca-
4,8,12-trienal (42): This was prepared from 41 (2.25 g, 3.74 mmol)
in the same manner as described for 20 to give 2.01 g of crude 42
as a colorless oil. Ϫ IR (film): ν˜max ϭ 2715 cmϪ1 (m, CHO), 1725
(s, CϭO), 1585 (w, CϭC), 1250 (m, SiϪC), 1200 (m, CϪO), 1150
(m, CϪO), 1125 (s, CϪO), 1080 (s, CϪO), 1065 (s, CϪO), 1035 (s,
5/3 H, 12-H3 (E)], 1.70 [s, 4/3 H, 12-H3 (Z)], 2.00Ϫ2.20 (m, 4 H,
6,7-H2), 2.04 (s, 3 H, ArCH3), 2.11 (s, 3 H, ArCH3), 2.25Ϫ2.40 (m,
2 H, 3-H2), 2.32 (s, 3 H, acetyl), 2.44 (t, J ϭ 7 Hz, 2 H, 2-H2), 3.11
(d, J ϭ 7 Hz, 2 H, 10-H2), 3.67 [s, 5/3 H, CO2CH3 (E)], 3.68 [s, 4/
3 H, CO2CH3 (Z)], 5.10Ϫ5.35 (m, 2 H, 5,9-H), 6.49 (s, 1 H, aro-
matic H), 6.55Ϫ6.63 (m, 1 H, OH). Ϫ 13C NMR (75.5 MHz,
CDCl3): δ ϭ 11.7, 12.9, 15.6, 15.7, 15.8, 20.4, 23.0, 25.6, 25.7, 28.2,
31.0, 32.7, 34.4, 34.5, 39.1, 51.6, 113.0, 113.1, 121.6, 121.9, 122.5,
124.6, 124.7, 129.45, 129.51, 130.5, 133.0, 133.2, 135.9, 136.2,
140.5, 151.78, 151.81, 169.9, 174.6, 174.7. Ϫ C23H32O5 (388.5):
calcd. C 71.11, H 8.30; found C 71.09, H 8.08.
1
CϪO). Ϫ H NMR (90 MHz, CDCl3): δ ϭ 0.03 (s, 9 H, SiMe3),
1.01 (t, J ϭ 9 Hz, 2 H, CH2Si), 1.40Ϫ2.25 (m, 14 H, THP,
6,7,10,11-H2), 1.60 (s, 6 H, 15,16-H3), 1.70 (s, 3 H, 17-H3), 2.17 (s,
3 H, ArCH3), 2.21 (s, 3 H, ArCH3), 2.25Ϫ2.65 (m, 4 H, 2,3-H2),
3.36 (d, J ϭ 7 Hz, 2 H, 14-H2), 3.40Ϫ4.20 (m, 2 H, THP), 3.86 (t,
J ϭ 9 Hz, 2 H, CH2CH2Si), 4.92 (s, 2 H, OCH2O), 5.00Ϫ5.45 (m,
4 H, 5,9,13-H, THP), 6.79 (s, 1 H, aromatic H), 9.75 (t, J ϭ 2 Hz,
1 H, CHO). This was employed in the next step without further
purification.
Methyl
(4E)-10-[2Ј-Acetoxy-3Ј,4Ј-dimethyl-5Ј-(2Љ,3Љ,4Љ-tri-O-
acetyl-1Љ-β--xylopyranosyloxy)phenyl]-4,8-dimethyldeca-4,8-
dienoate (40): This was prepared from 39 (400 mg, 1.03 mmol) in
the same manner as described for 25 to give 423 mg of crude 40 as
a colorless oil. Ϫ IR (film): ν˜max ϭ 1755 cmϪ1 (s, CϭO), 1585, (w,
CϭC), 1225 (s, CϪO), 1195 (s, CϪO), 1060 (s, CϪO), 1040 (s,
CϪO). This was employed in the next step without further purifi-
cation.
(6E,10E)-16-{3Ј,4Ј-Dimethyl-5Ј-tetrahydropyranyloxy-2Ј-[2-
( t r i m e t hy l s i ly l ) e t h ox y m e t h ox y ] p h en y l } - 2 , 6, 10 , 1 4 -
tetramethylhexadeca-1,6,10,14-tetraen-3-ol (43): To a stirred solu-
tion of 2-bromopropene (1.53 g, 12.6 mmol) in THF (40 ml) was
added dropwise s-butyllithium (1.03  in cyclohexane, 9.23 ml, 9.51
mmol) at Ϫ78°C under argon, and the mixture was stirred at
Ϫ78°C for 30 min. Then a solution of 42 (1.90 g, 3.17 mmol) in
THF (20 ml) was added dropwise, and the stirring was continued
for 2 h at room temperature. After the addition of water (50 ml),
the mixture was extracted three times with diethyl ether (50 ml).
The combined ethereal extracts were successively washed with
water and brine, dried with Na2SO4, and concentrated in vacuo.
The residue was purified by chromatography on silica gel (50 g,
hexane/ethyl acetate, 20:1) to give 0.40 g (21%) of the recovered 42
and 1.42 g (70%) of 43 as a colorless oil; n2D3 ϭ 1.5152. Ϫ IR (film):
ν˜max ϭ 3475 cmϪ1 (m, OϪH), 1250 (m, SiϪC), 1200 (m, CϪO),
1150 (m, CϪO), 1125 (s, CϪO), 1080 (s, CϪO), 1065 (s, CϪO),
(4E)-10-[2Ј-Hydroxy-3Ј,4Ј-dimethyl-5Ј-(1Љ-β--xylopyrano-
syloxy)phenyl]-4,8-dimethyldeca-4,8-dienoic Acid (4): This was pre-
pared from crude 40 (423 mg) in the same manner as described for
2 to give 200 mg (42% based on 39) of 4 as a colorless amorphous
solid. Ϫ [α]2D5 ϭ Ϫ17 (c ϭ 0.18, MeOH). Ϫ Rf ϭ 0.62 (iBuOH/
MeOH/H2O, 8:1:1). Ϫ IR (KBr): ν˜max ϭ 3440 cmϪ1 (s, OϪH), 2915
(m), 1715 (m, CϭO), 1645 (m), 1480 (m), 1455 (m), 1425 (m), 1385
(m), 1215 (m, CϪO), 1160 (m, CϪO), 1075 (m, CϪO), 1055 (s,
CϪO), 985 (m), 845 (m). Ϫ 1H NMR (300 MHz, CD3OD): δ ϭ
1.61 (s, 3 H, 11-H3), 1.71 [s, 5/3 H, 12-H3 (E)], 1.76 [s, 4/3 H, 12-
H3 (Z)], 2.00Ϫ2.20 (m, 4 H, 6,7-H2), 2.14 (s, 3 H, 13 or 14-H3),
2.16 (s, 3 H, 13 or 14-H3), 2.24 (t, J ϭ 7 Hz, 2 H, 3-H2), 2.31 (br.
t, J ϭ 7 Hz, 2 H, 2-H2), 3.19, 3.20 (each t, J ϭ 10 Hz, total 1 H,
5Љa-H), 3.27 (d, J ϭ 7 Hz, 2 H, 10-H2), 3.38 (t, J ϭ 8 Hz, 1 H, 3Љ-
H), 3.44 (t, J ϭ 8 Hz, 1 H, 2Љ-H), 3.58 (ddd, J ϭ 5 Hz, JЈ ϭ 8 Hz,
JЉ ϭ 10 Hz, 1 H, 4Љ-H), 3.87 (dd, J ϭ 5 Hz, JЈ ϭ 10 Hz, 1 H, 5Љe-
H), 4.60 (d, J ϭ 8 Hz, 1 H, 1Љ-H), 5.17, 5.19 (each t, J ϭ 7 Hz,
total 1 H, 5-H), 5.31, 5.33 (each t, J ϭ 7 Hz, total 1 H, 9-H), 6.71
(s, 1 H, 6Ј-H). Ϫ 13C NMR (75.5 MHz, CD3OD): δ ϭ 12.7, 12.9,
16.06, 16.11, 16.3, 23.8, 27.5, 27.6, 29.4, 29.6, 32.8, 34.1, 34.2, 35.8,
35.9, 40.7, 66.9, 71.1, 74.9, 77.9, 105.07, 105.10, 116.46, 116.53,
124.1, 124.5, 125.8, 126.1, 126.2, 126.56, 126.59, 127.7, 127.8,
134.9, 135.1, 136.9, 137.2, 148.8, 150.5, 150.6, 178.3. Ϫ MS (70
1
1035 (s, CϪO). Ϫ H NMR (90 MHz, CDCl3): δ ϭ 0.03 (s, 9 H,
SiMe3), 1.01 (t, J ϭ 9 Hz, 2 H, CH2Si), 1.55Ϫ2.30 (m, 19 H, THP,
4,5,8,9,12,13-H2, OH), 1.61 (s, 6 H, 18,19-H3), 1.72 (s, 6 H, 17,20-
H3), 2.15 (s, 3 H, ArCH3), 2.21 (s, 3 H, ArCH3), 3.32 (d, J ϭ 7
Hz, 2 H, 16-H2), 3.40Ϫ4.20 (m, 3 H, 3-H, THP), 3.87 (t, J ϭ 9
Hz, 2 H, CH2CH2Si), 4.80Ϫ5.45 (m, 6 H, 1-H2, 7,11,15-H, THP),
4.92 (s, 2 H, OCH2O), 6.78 (s, 1 H, aromatic H). Ϫ C39H64O5Si
(641.0): calcd. C 73.08, H 10.06; found C 73.03, H 10.06.
Ethyl (4E,8E,12E)-18-{3Ј,4Ј-Dimethyl-5Ј-tetrahydropyranyloxy-
eV); m/z (%): 464 (1) [Mϩ], 446 (1), 332 (97), 205 (17), 189 (53), 2Ј-[2-(trimethylsilyl)ethoxymethoxy]phenyl}-4,8,12,16-
151 (100). Ϫ HRMS: C25H36O8 [Mϩ]: calcd. 464.2410, found tetramethyloctadeca-4,8,12,16-tetraenoate (44): To a stirred solution
464.2418. This material is an inseparable mixture of (8E) and (8Z) of 43 (1.35 g, 2.11 mmol) in MeCH(OEt)3 (10.0 g, 61.3 mmol) was
isomers (1.3:1).
added a catalytic amount of propionic acid (10 mg). The stirring
Liebigs Ann./Recueil 1997, 43Ϫ55
51

S. Takanashi, K. Mori
FULL PAPER
was continued for 1 h at 140°C under the condition for distillative CϭC), 1240 (m, CϪO), 1190 (s, CϪO), 1080 (m, CϪO). Ϫ 1H
removal of ethanol. Then the mixture was concentrated to remove NMR (300 MHz, CDCl3): δ ϭ 1.26 (t, J ϭ 7 Hz, 3 H, CH3CH2),
MeCH(OEt)3. After cooling, the mixture was diluted with diethyl
ether (150 ml). The ethereal solution was successively washed with 1 Hz, 4/3 H, 22-H3 (Z)], 1.90Ϫ2.15 (m, 12 H, 6,7,10,11,14,15-H2),
water and brine, dried with Na2SO4, and concentrated in vacuo. 2.03 (s, 3 H, ArCH3), 2.11 (s, 3 H, ArCH3), 2.25-2.35 (m, 2 H, 3-
The residue was purified by chromatography on silica gel (70 g, H2), 2.307 [s, 4/3 H, acetyl (Z)], 2.313 [ s, 5/3 H, acetyl (E)], 2.39
1.60 (s, 9 H, 19,20,21-H3), 1.66 [s, 5/3 H, 22-H3 (E)], 1.73 [d, J ϭ
hexane/ethyl acetate, 20:1) to give 1.31 g (83%) of 44 as a colorless
(br. t, J ϭ 7 Hz, 2 H, 2-H2), 3.11 (d, J ϭ 7 Hz, 2 H, 18-H2), 4.13
(q, J ϭ 7 Hz, 2 H, CH3CH2), 5.05Ϫ5.25 (m, 4 H, 5,9,13,17-H),
oil; n2D4 ϭ 1.5080. Ϫ IR (film): ν˜max ϭ 1735 cmϪ1 (s, CϭO), 1250
(s, SiϪC), 1200 (s, CϪO), 1150 (s, CϪO), 1125 (s, CϪO), 1080 (s, 5.49 [s, 5/9 H, OH (E)], 5.51 [s, 4/9 H, OH (Z)], 6.47 (s, 1 H, aro-
CϪO), 1065 (s, CϪO), 1035 (s, CϪO). Ϫ 1H NMR (300 MHz, matic H). Ϫ 13C NMR (75.5 MHz, CDCl3): δ ϭ 11.9, 13.1, 14.2,
CDCl3): δ ϭ 0.04 (s, 9 H, SiMe3), 1.01 (br. t, J ϭ 9 Hz, 2 H, 15.8, 15.9, 16.1, 20.5, 23.4, 26.4, 26.5, 28.46, 28.54, 31.9, 33.2, 34.6,
CH2Si), 1.25 (t, J ϭ 8 Hz, 3 H, CH3CH2), 1.55Ϫ1.75 (m, 3 H, 39.5, 39.6, 39.7, 60.4, 113.28, 113.34, 121.48, 121.53, 122.4, 123.9,
THP), 1.59, 1.61 (each s, total 9 H, 19,20,21-H3), 1.71 [s, 5/3 H, 124.1, 124.3, 125.1, 129.7, 129.8, 130.86, 130.92, 133.1, 134.7,
22-H3 (E)], 1.73 [d, J ϭ 1 Hz, 4/3 H, 22-H3 (Z)], 1.80Ϫ1.90 (m , 2
134.8, 135.0, 135.3, 136.60, 136.63, 140.8, 140.9, 151.5, 169.9,
H, THP), 1.90Ϫ2.15 (m, 13 H, 6,7,10,11,14,15-H2, THP), 2.15 (s, 173.9. Ϫ C34H50O5 (538.8): calcd. C 75.80, H 9.36; found C 75.66,
3 H, ArCH3), 2.21 (s, 3 H, ArCH3), 2.29 (t, J ϭ 7 Hz, 2 H, 3-H2), H 9.06.
2.39 (br. t, J ϭ 7 Hz, 2 H, 2-H2), 3.28Ϫ3.45 (m, 2 H, 18-H2),
Ethyl (4E,8E,12E)-18-[2Ј-Acetoxy-3Ј,4Ј-dimethyl-5Ј-(2Љ,3Љ,4Љ-
3.52Ϫ3.64 (m, 1 H, THP), 3.80Ϫ4.00 (m, 1 H, THP), 3.86 (br. t,
tri-O-acetyl-1Љ-β- -xylopyranosyloxy)phenyl]-4,8,12,16-
J ϭ 9 Hz, 2 H, CH2CH2Si), 4.12 (q, J ϭ 8 Hz, 2 H, CH3CH2),
tetramethyloctadeca-4,8,12,16-tetraenoate (48): This was prepared
4.91 (s, 2 H, OCH2O), 5.05Ϫ5.20 (m, 3 H, 5,9,13-H), 5.25Ϫ5.35
from 47 (400 mg, 0.742 mmol) in the same manner as described
(m, 2 H, 17-H, THP), 6.78 [s, 5/9 H, aromatic H (E)], 6.79 [s, 4/9
for 25 to give 378 mg of crude 48 as a colorless oil. Ϫ IR (film):
H, aromatic H (Z)]. Ϫ 13C NMR (75.5 MHz, CDCl3): δ ϭ Ϫ1.5,
ν˜max ϭ 1760 cmϪ1 (s, CϭO), 1245 (s, CϪO), 1220 (s, CϪO), 1080
(s, CϪO), 1060 (s, CϪO), 1040 (s, CϪO). This was employed in
the next step without further purification.
12.2, 13.5, 14.2, 15.8, 15.9, 16.2, 18.2, 19.1, 23.4, 25.3, 26.6, 26.8,
28.7, 30.6, 32.1, 33.2, 34.6, 39.5, 39.63, 39.66, 39.72, 60.1, 62.0,
67.2, 96.8, 97.7, 113.42, 113.48, 123.0, 123.7, 124.06, 124.14, 124.3,
124.75, 124.80, 125.0, 130.7, 132.0, 133.1, 134.60, 134.65, 134.9,
135.1, 135.9, 148.1, 148.2, 151.3, 173.4. Ϫ C43H70O6Si (711.1):
calcd. C 72.63, H 9.92; found C 72.14, H 9.77.
(4E,8E,12E)-18-[2Ј-Hydroxy-3Ј,4Ј-dimethyl-5Ј-(1ЈЈ-β--xylopy-
ranosyloxy)phenyl]-4,8,12,16-tetramethyloctadeca-4,8,12,16-tetra
enoic Acid (5): This was prepared from crude 48 (378 mg) in the
same manner as described for 2 to give 208 mg (47% based on 47)
of 5 as a colorless amorphous solid. Ϫ [α]2D5 ϭ Ϫ15 (c ϭ 0.079,
MeOH). Ϫ Rf ϭ 0.69 (iBuOH/MeOH/H2O, 8:1:1). Ϫ IR (KBr):
ν˜max ϭ 3430 cmϪ1 (s, OϪH), 2925 (s), 2860 (m), 1715 (s, CϭO),
1550 (w, CϭC), 1480 (m), 1445 (m), 1380 (m), 1280 (m, CϪO),
1255 (m, CϪO), 1215 (m, CϪO), 1165 (m, CϪO), 1100 (m, CϪO),
1050 (s, CϪO), 985 (m), 845 (w). Ϫ 1H NMR (300 MHz, CD3OD):
δ ϭ 1.58, 1.60 (each s, total 9 H, 19,20,21-H3), 1.71 [s, 5/3 H, 22-
H3 (E)], 1.76 [s, 4/3 H, 22-H3 (Z)], 1.90Ϫ2.20 (m, 12 H,
6,7,10,11,14,15-H2), 2.14 (s, 3 H, 23 or 24-H3), 2.16 (s, 3 H, 23 or
24-H3), 2.25 (t, J ϭ 7 Hz, 2 H, 3-H2), 2.35 (br. t, J ϭ 7 Hz, 2 H,
2-H2), 3.18, 3.20 (each t, J ϭ 10 Hz, total 1 H, 5Љa-H), 3.25Ϫ3.35
(m, 2 H, 18-H2), 3.37 (t, J ϭ 7 Hz, 1 H, 3Љ-H), 3.43 (t, J ϭ 7 Hz,
1 H, 2Љ-H), 3.57 (ddd, J ϭ 5 Hz, JЈ ϭ 7 Hz, JЉ ϭ 10 Hz, 1 H, 4Љ-
H), 3.86, 3.87 (each dd, J ϭ 5 Hz, JЈ ϭ 10 Hz, total 1 H, 5Љe-H),
4.59, 4.60 (each d, J ϭ 8 Hz, total 1 H, 1Љ-H), 5.05Ϫ5,20 (m, 3 H,
5,9,13-H), 5.32 (t, J ϭ 7 Hz, 1 H, 17-H), 6.72 (s, 1 H, 6Ј-H). Ϫ 13C
Ethyl (4E,8E,12E)-18-(2Ј-Hydroxy-3Ј,4Ј-dimethyl-5Ј-tetrahydro-
pyranyloxyphenyl)-4,8,12,16-tetramethyloctadeca-4,8,12,16-tetra-
enoate (45): This was prepared from 44 (1.10 g, 1.55 mmol) in the
same manner as described for 22 to give 1.53 g of crude 45 as a
brown oil. Ϫ IR (film): ν˜max ϭ 3420 cmϪ1 (s, OϪH), 1735 (m, Cϭ
1
O), 1200, (s, CϪO), 1170 (s, CϪO), 1065 (m, CϪO). Ϫ H NMR
(90 MHz, CDCl3): δ ϭ 1.25 (t, J ϭ 7 Hz, 3 H, CH3CH2), 1.55Ϫ2.40
(m, 25 H, 2,3,6,7,10,11,14,15-H2, 22-H3, THP), 1.60 (s, 9 H,
19,20,21-H3), 2.16 (s, 6 H, ArCH3), 3.31 (d, J ϭ 7 Hz, 2 H, 18-
H2), 3.40Ϫ4.00 (m, 2 H, THP), 4.12 (q, J ϭ 7 Hz, 2 H, CH3CH2),
4.90Ϫ5.40 (m, 6 H, 5,9,13,17-H, THP, OH), 6.72 (s, 1 H, aromatic
H). This was employed in the next step without further purifi-
cation.
Ethyl (4E,8E,12E)-18-(2Ј-Acetoxy-3Ј,4Ј-dimethyl-5Ј-tetrahydro-
dropyranyloxyphenyl)-4,8,12,16-tetramethyloctadeca-4,8,12,16-
tetraenoate (46): This was prepared from crude 45 (1.53 g) in the
same manner as described for 23 to give 873 mg (90% based on NMR (75.5 MHz, CD3OD): δ ϭ 12.7, 12.9, 16.06, 16.14, 16.18,
44) of 46 as a yellowish oil; n2D3 ϭ 1.5069. Ϫ IR (film): ν˜max ϭ 1760
16.3, 23.8, 27.5, 27.62, 27.68, 27.74, 29.5, 29.6, 33.0, 34.5, 36.0,
cmϪ1 (s, CϭO), 1735 (s, CϭO), 1585 (w, CϭC), 1220 (m, CϪO), 40.7, 40.8, 41.0, 66.9, 71.1, 75.0, 78.0, 105.1, 116.5, 123.9, 124.4,
1190 (s, CϪO), 1150 (w, CϪO), 1125 (m, CϪO), 1080 (m, CϪO), 125.4, 125.60, 125.62, 126.0, 126.11, 126.13, 126.5, 126.6, 127.7,
1
1040 (m, CϪO). Ϫ H NMR (90 MHz, CDCl3): δ ϭ 1.23 (t, J ϭ 127.9, 134.7, 135.68, 135.72, 136.0, 136.2, 137.1, 137.4, 148.9,
7 Hz, 3 H, CH3CH2), 1.40Ϫ2.40 (m, 22 H, 2,3,6,7,10,11,14,15-H2, 150.58, 150.60, 178.4. Ϫ MS (70 eV); m/z (%): 600 (2) [Mϩ], 582
THP), 1.60 (s, 9 H, 19,20,21-H3), 1.68 [s, 5/3 H, 22-H3 (E)], 1.71 (2), 564 (1), 482 (20), 468 (100), 255 (25), 189 (100), 151 (100), 81
[br. s, 4/3 H, 22-H3 (Z)], 2.02 (s, 3 H, ArCH3), 2.18 (s, 3 H, ArCH3), (100). Ϫ HRMS: C35H52O8 [Mϩ]: calcd. 600.3662, found 600.3672.
2.29 (s, 3 H, acetyl), 3.17 (d, J ϭ 7 Hz, 2 H, 18-H2), 3.40Ϫ4.00 (m, This material is an inseparable mixture of (16E) and (16Z) iso-
2 H, THP), 4.12 (q, J ϭ 7 Hz, 2 H, CH3CH2), 5.00Ϫ5.40 (m, 5 H,
5,9,13,17-H, THP), 6.82 (s, 1 H, aromatic H). Ϫ C39H58O6 (622.9):
calcd. C 75.20, H 9.39; found C 74.88, H 9.63.
mers (1.3:1).
Methyl (4E,8E)-14-[2Ј-Hydroxy-3Ј,4Ј-dimethyl-5Ј-(1Љ-β--xylo-
pyranosyloxy)phenyl]-4,8,12-trimethyltetradeca-4,8,12-tri-
enoate (6): To a stirred and ice-cooled solution of mixture of lurl-
Ethyl
(4E,8E,12E)-18-(2Ј-Acetoxy-5Ј-hydroxy-3Ј,4Ј-dimethyl-
phenyl)-4,8,12,16-tetramethyloctadeca-4,8,12,16-tetraenoate enic acid (1) and its (12Z) isomer (50 mg) in methanol (1.0 ml) was
(47): This was prepared from 46 (700 mg, 1.12 mmol) in the same added a solution of diazomethane (20.2 mmol) in diethyl ether (2
manner as described for 24 to give 601 mg (quantitative) of 47 as
ml). The stirring was continued for 2 h at room temperature. Then
a yellowish oil; nD23 ϭ 1.5171. Ϫ IR (film): ν˜max ϭ 3435 cmϪ1 (m, the mixture was concentrated in vacuo. The residue was purified
OϪH), 1760 (s, CϭO), 1735 (s, CϭO), 1710 (m, CϭO), 1590 (w, by chromatography on silica gel (2.5 g, chloroform/methanol, 30:1)
52
Liebigs Ann./Recueil 1997, 43Ϫ55

Pheromone Synthesis, CLXXXVII
FULL PAPER
to give 51 mg (99%) of 6 as a colorless amorphous solid. Ϫ [α]D24
ϭ
in 1-butanol (1.5 ml). The stirring was continued for 6 h at room
Ϫ17 (c ϭ 0.040, MeOH). Ϫ Rf ϭ 0.45 (CHCl3/MeOH, 7:1). Ϫ IR temperature. After the addition of chloroform (150 ml), the mixture
(KBr): ν˜max ϭ 3460 cmϪ1 (s, OϪH), 2920 (s), 2855 (m), 1740 (s,
CϭO), 1485 (m), 1445 (m), 1385 (m), 1320 (m), 1220 (m, CϪO),
was washed with brine, dried with Na2SO4, and concentrated in
vacuo. The residue was purified by chromatography on silica gel
1190 (m, CϪO), 1150 (m, CϪO), 1100 (m, CϪO), 1075 (m, CϪO), (25 g, chloroform/methanol, 100:1) to give 152 mg (46% based on
1
1040 (s, CϪO), 970 (m), 895 (w), 855 (w). Ϫ H NMR (300 MHz, 32) of 8 as a colorless amorphous solid. Ϫ [α]2D4 ϭ Ϫ15 (c ϭ 0.21,
CD3OD): δ ϭ 1.60 (s, 6 H, 15,16-H3), 1.71 [s, 9/5 H, 17-H3 (E)], MeOH). Ϫ Rf ϭ 0.45 (CHCl3/MeOH, 7:1). Ϫ IR (KBr): ν˜max
1.76 [s, 6/5 H, 17-H3 (Z)], 1.90Ϫ2.20 (m, 8 H, 6,7,10,11-H2), 2.14
ϭ
3380 cmϪ1 (s, OϪH), 2965 (s), 2920 (s), 2860 (m), 1735 (s, CϭO),
(s, 3 H, 18 or 19-H3), 2.16 (s, 3 H, 18 or 19-H3), 2.24 (t, J ϭ 7 Hz, 1480 (m), 1455 (m), 1425 (m), 1385 (m), 1320 (m), 1220 (m, CϪO),
2 H, 3-H2), 2.38 (t, J ϭ 7 Hz, 2 H, 2-H2), 3.19, 3.20 (each t, J ϭ 1190 (m, CϪO), 1150 (s, CϪO), 1100 (s, CϪO), 1075 (s, CϪO),
10 Hz, total 1 H, 5Љa-H), 3.25Ϫ3.35 (m, 2 H, 14-H2), 3.38 (t, J ϭ
7 Hz, 1 H, 3Љ-H), 3.44 (t, J ϭ 7 Hz, 1 H, 2Љ-H), 3.50Ϫ3.65 (m, 1 (300 MHz, CD3OD):
H, 4Љ-H), 3.62 (s, 3 H, CO2CH3), 3.86, 3.88 (each dd, J ϭ 5 Hz, CH3CH2CH2CH2), 1.36 (sext, J ϭ 7 Hz, 2 H, CH3CH2CH2CH2),
1040 (s, CϪO), 970 (m), 890 (w), 860 (w), 835 (w). Ϫ 1H NMR
δ
ϭ 0.93 (t, J ϭ 7 Hz, 3 H,
JЈ ϭ 10 Hz, total 1 H, 5Љe-H), 4.60 (d, J ϭ 7 Hz, 1 H, 1Љ-H), 1.55Ϫ1.65 (m, 2 H, CH3CH2CH2CH2), 1.59 (s, 6 H, 15,16-H3),
5.08Ϫ5.20 (m, 2 H, 5,9-H), 5.33 (t, J ϭ 7 Hz, 1 H, 13-H), 6.72 (s, 1.71 [s, 5/3 H, 17-H3 (E)], 1.76 [s, 4/3 H, 17-H3 (Z)], 1.90Ϫ2.20 (m,
1 H, 6Ј-H). Ϫ 13C NMR (75.5 MHz, CD3OD): δ ϭ 12.7, 12.9,
8 H, 6,7,10,11-H2), 2.14 (s, 3 H, 18 or 19-H3), 2.16 (s, 3 H, 18 or
16.0, 16.1, 16.2, 16.3, 23.8, 27.5, 27.6, 27.7, 29.4, 29.6, 32.9, 33.9, 19-H3), 2.25 (t, J ϭ 7 Hz, 2 H, 3-H2), 2.39 (br. t, J ϭ 7 Hz, 2 H,
35.7, 40.6, 40.9, 52.0, 66.9, 71.1, 74.9, 77.9, 79.4, 105.1, 116.5, 2-H2), 3.19, 3.20 (each t, J ϭ 10 Hz, total 1 H, 5Љa-H), 3.25Ϫ3.35
123.9, 124.4, 125.5, 126.0, 126.1, 126.2, 126.51, 126.54, 127.2, (m, 2 H, 14-H2), 3.38 (t, J ϭ 8 Hz, 1 H, 3Љ-H), 3.44 (t, J ϭ 8 Hz,
127.6, 127.8, 134.4, 135.8, 136.0, 137.1, 137.3, 148.9, 150.6, 175.6. 1 H, 2Љ-H), 3.58 (ddd, J ϭ 5 Hz, JЈ ϭ 8 Hz, JЉ ϭ 10 Hz, 1 H, 4Љ-
Ϫ MS (70 eV); m/z (%): 546 (2) [Mϩ], 414 (100), 346 (8), 206 (10), H), 3.86, 3.87 (each dd, J ϭ 5 Hz, JЈ ϭ 10 Hz, total 1 H, 5Љe-H),
189 (38), 151 (58), 81 (34). Ϫ HRMS: C31H46O8 [Mϩ]: calcd. 4.04 (t, J ϭ 7 Hz, 2 H, CH3CH2CH2CH2), 4.60 (d, J ϭ 8 Hz, 1 H,
546.3193, found 546.3182. This material is an inseparable mixture 1Љ-H), 5.08Ϫ5.20 (m, 2 H, 5,9-H), 5.32 (t, J ϭ 7 Hz, 1 H, 13-H),
of (12E) and (12Z) isomers (1.5:1).
6.72 (s, 1 H, 6Ј-H). Ϫ 13C NMR (75.5 MHz, CD3OD): δ ϭ 11.8,
12.0, 13.1, 15.08, 15.19, 15.24, 15.4, 19.2, 22.9, 26.56, 26.62, 26.74,
28.7, 30.9, 33.2, 34.8, 39.7. 39.9, 64.3, 66.0, 70.1, 74.0, 77.0, 104.2,
115.6, 123.0, 123.5, 124.5, 125.07, 125.11, 125.3, 125.6, 126.7,
126.8, 133.4, 133.5, 134.9, 135.1, 136.1, 136.3, 147.9, 149.60,
149.63, 174.3. Ϫ MS (70 eV); m/z (%): 588 (1) [Mϩ], 542 (1), 514
(6), 456 (75), 388 (12), 206 (17), 189 (52), 151 (100), 81 (25). Ϫ
HRMS: C34H52O8 [Mϩ]: calcd. 588.3662, found 588.3652. This ma-
terial is an inseparable mixture of (12E) and (12Z) isomers (1.3:1)
and is contaminated with about 10% of an inseparable impurity.
Ethyl (4E,8E)-14-[2Ј-Hydroxy-3Ј,4Ј-dimethyl-5Ј-(1Љ-β--xylopy-
ranosyloxy)phenyl]-4,8,12-trimethyltetradeca-4,8,12-trienoate (7):
To a stirred solution of crude 49 (150 mg) in ethanol (2.0 ml) was
added a solution of sodium ethoxide (50 mg) in ethanol (1.0 ml).
The stirring was continued for 6 h at room temperature. After the
addition of chloroform (100 ml), the mixture was washed with
brine, dried with Na2SO4, and concentrated in vacuo. The residue
was purified by chromatography on silica gel (25 g, chloroform/
methanol, 100:1) to give 82 mg (53% based on 32) of 7 as a color-
less amorphous solid. Ϫ [α]2D4 ϭ Ϫ15 (c ϭ 0.18, MeOH). Ϫ Rf ϭ
2-Bromo-4-tetrahydropyranyloxyphenol (51): To a stirred and ice-
0.45 (CHCl3/MeOH, 7:1). Ϫ IR (KBr): ν˜max ϭ 3380 cmϪ1 (s, cooled solution of 50 (9.00 g, 47.6 mmol) in THF (230 ml) were
OϪH), 2975 (m), 2920 (s), 2860 (m), 1735 (s, CϭO), 1485 (m), 1445 added 3,4-dihydro-2H-pyran (4.80 g, 57.1 mmol) and p-toluenesul-
(m), 1425 (m), 1385 (m), 1320 (m), 1220 (m, CϪO), 1190 (m, fonic acid monohydrate (100 mg, 0.582 mmol). The stirring was
CϪO), 1150 (s, CϪO), 1100 (s, CϪO), 1075 (s, CϪO), 1040 (s, continued for 20 h at room temperature. Then the mixture was
CϪO), 970 (m), 890 (w), 860 (w). Ϫ 1H NMR (300 MHz, CD3OD): diluted with a saturated NaHCO3 solution (200 ml) and extracted
δ ϭ 1.21 (t, J ϭ 7 Hz, 3 H, CH3CH2), 1.59 (s, 6 H, 15,16-H3), 1.71 three times with diethyl ether (200 ml). The combined ethereal ex-
[s, 5/3 H, 17-H3 (E)], 1.75 [s, 4/3 H, 17-H3 (Z)], 1.90Ϫ2.20 (m, 8 tracts were successively washed with water and brine, dried with
H, 6,7,10,11-H2), 2.14 (s, 3 H, 18 or 19-H3), 2.16 (s, 3 H, 18 or 19- Na2SO4, and concentrated in vacuo. The residue was purified by
H3), 2.24 (t, J ϭ 7 Hz, 2 H, 3-H2), 2.37 (br. t, J ϭ 7 Hz, 2 H, 2-
H2), 3.19, 3.22 (each t, J ϭ 10 Hz, total 1 H, 5Љa-H), 3.23Ϫ3.33
chromatography on silica gel (400 g, hexane/ethyl acetate, 30:1) to
give 3.77 g of the recovered 50 and 8.62 g of crude 51 as a colorless
(m, 2 H, 14-H2), 3.39 (t, J ϭ 8 Hz, 1 H, 3Љ-H), 3.45 (t, J ϭ 8 Hz, oil. Ϫ IR (film): ν˜max ϭ 3335 cmϪ1 (s, OϪH), 1200 (s, CϪO), 1120
1 H, 2Љ-H), 3.58 (ddd, J ϭ 5 Hz, JЈ ϭ 8 Hz, JЉ ϭ 10 Hz, 1 H, 4Љ- (s, CϪO), 1110 (s, CϪO), 1075 (m, CϪO), 1035 (s, CϪO), 1020 (s,
H), 3.86, 3.87 (each dd, J ϭ 5 Hz, JЈ ϭ 10 Hz, total 1 H, 5Љe-H), CϪO). Ϫ 1H NMR (90 MHz, CDCl3): δ ϭ 1.30Ϫ2.10 (m, 6 H,
4.07 (q, J ϭ 7 Hz, 2 H, CH3CH2), 4.595, 4.600 (each d, J ϭ 8 Hz,
THP), 3.30Ϫ3.75 (m, 1 H, THP), 3.75Ϫ4.10 (m, 1 H, THP), 5.26
total 1 H, 1Љ-H), 5.05Ϫ5.20 (m, 2 H, 5,9-H), 5.32 (t, J ϭ 7 Hz, 1 (br. s, 1 H, THP), 5.77 (s, 1 H, OH), 5.89 (br. s, 2 H, 5,6-H), 7.22
H, 13-H), 6.72 (s, 1 H, 6Ј-H). Ϫ 13C NMR (75.5 MHz, CD3OD): (t, J ϭ 2 Hz, 1 H, 3-H). This was employed in the next step without
δ ϭ 12.7, 12.9, 14.6, 16.0, 16.2, 16.3, 23.8, 27.5, 27.6, 27.7, 29.5, further purification.
29.6, 32.9, 34.1, 35.8, 40.6, 40.9, 61.4, 66.9, 71.1, 74.9, 77.9, 105.1,
116.5, 123.9, 124.5, 125.5, 126.02, 126.05, 126.2, 126.51, 126.54,
1-Bromo-5-tetrahydropyranyloxy-2-[2-(trimethylsilyl)-
ethoxymethoxy]benzene (52): To a stirred solution of crude 51 (4.50
g) in dichloromethane (45 ml) were added dropwise N,N-diisopro-
pylethylamine (6.14 g, 49.5 mmol) and 2-(trimethylsilyl)ethoxy-
methyl chloride (4.13 g, 24.7 mmol) under argon. The stirring was
continued for 3 h at room temperature. Then the mixture was di-
luted with a saturated NaHCO3 solution (50 ml) and extracted
three times with dichloromethane (50 ml). The combined extracts
127.6, 127.8, 134.39, 134.42, 135.8, 136.0, 137.1, 137.3, 148.9,
150.54, 150.56, 175.2. Ϫ MS (70 eV); m/z (%): 560 (1) [Mϩ], 514
(1), 428 (100), 189 (49), 151 (83), 81 (32). Ϫ HRMS: C32H48O8
[Mϩ]: calcd. 560.3349, found 560.3344. This material is an insepa-
rable mixture of (12E) and (12Z) isomers (1.3:1) and is contami-
nated with about 10% of an inseparable impurity.
Butyl (4E,8E)-14-[2Ј-Hydroxy-3Ј,4Ј-dimethyl-5Ј-(1Љ-β--xylo- were successively washed with water and brine, dried with Na2SO4,
pyranosyloxy)phenyl]-4,8,12-trimethyltetradeca-4,8,12-trienoate (8):
To a stirred and ice-cooled solution of crude 49 (300 mg) in 1-
and concentrated in vacuo. The residue was purified by chromatog-
raphy on silica gel (250 g, hexane/ethyl acetate, 50:1) to give 4.37 g
butanol (3.0 ml) was added a solution of sodium butoxide (50 mg) (44% based on 50) of 52 as a colorless oil; n2D3 ϭ 1.5151. ϪIR
Liebigs Ann./Recueil 1997, 43Ϫ55
53

S. Takanashi, K. Mori
FULL PAPER
(film): ν˜max ϭ 1600 (w, CϭC), 1250 cmϪ1 (m, SiϪC), 1200 (s,
4 H, 2,3-H2), 2.26 (s, 3 H, acetyl), 3.19 (d, J ϭ 7 Hz, 2 H, 14-H2),
3.40Ϫ4.05 (m, 2 H, THP), 3.64 (s, 3 H, CO2CH3), 5.00Ϫ5.30 (s, 3
CϪO), 1180 (m, CϪO), 1105 (s, CϪO), 1095 (s, CϪO), 1035 (s,
1
CϪO). Ϫ H NMR (90 MHz, CDCl3): δ ϭ 0.10 (s, 9 H, SiMe3), H, 5,9,13-H), 5.35 (br. t, J ϭ 3 Hz, 1 H, THP), 6.89 (s, 3 H, aro-
1.07 (t, J ϭ 9 Hz, 2 H, CH2Si), 1.60Ϫ2.15 (m, 3 H, THP),
matic H). Ϫ C31H44O6 (512.7): calcd. C 72.63, H 8.65; found C
3.50Ϫ4.20 (m, 2 H, THP), 3.92 (t, J ϭ 9 Hz, 2 H, CH2CH2Si), 72.72, H 8.76.
5.32 (s, 2 H, OCH2O), 5.32Ϫ5.50 (m, 1 H, THP), 7.03 (dd, J ϭ 3
Hz, JЈ ϭ 11 Hz, 1 H, 4-H), 7.21 (d, J ϭ 11 Hz, 1 H, 3-H), 7.39 (d,
J ϭ 3 Hz, 1 H, 6-H). Ϫ C17H27O4BrSi (403.4): calcd. C 50.62, H
6.75; found C 50.50, H 6.71.
Methyl
(4E,8E)-14-(2Ј-Acetoxy-5Ј-hydroxyphenyl)-4,8,12-tri-
methyltetradeca-4,8,12-trienoate (57): This was prepared from 56
(1.00 g, 1.95 mmol) in the same manner as described for 24 to give
735 mg (88%) of 57 as a yellowish oil; n2D3 ϭ 1.5172. Ϫ IR (film):
1-Tetrahydropyranyloxy-4-[2-(trimethylsilyl)ethoxymethoxy]-3-
ν˜max ϭ 3430 cmϪ1 (m, OϪH), 1760 (s, CϭO), 1740 (s, CϭO), 1590
1
(trimethylstannyl)benzene (53): To a stirred solution of 52 (2.50 g, (m, CϭC), 1215 (s, CϪO), 1185 (s, CϪO), 1100 (w, CϪO). Ϫ H
6.20 mmol) in THF (25 ml) was added dropwise butyllithium (1.59 NMR (300 MHz, CDCl3): δ ϭ 1.59 (s, 6 H, 15,16-H3), 1.66 [s, 5/3
 in hexane, 5.85 ml, 9.30 mmol) at Ϫ50°C under argon, and the H, 17-H3 (E)], 1.72 [s, 4/3 H, 17-H3 (Z)], 1.90Ϫ2.20 (m, 8 H,
mixture was stirred at Ϫ50°C for 30 min. Then trimethylstannyl 6,7,10,11-H2), 2.22Ϫ2.32 (m, 2 H, 3-H2), 2.27 (s, 3 H, acetyl), 2.42
chloride (1.85 g, 9.30 mmol) was added, and the stirring was con-
(t, J ϭ 7 Hz, 2 H, 2-H2), 3.15 (d, J ϭ 7 Hz, 2 H, 14-H2), 3.66 (s,
tinued for 3 h at room temperature. After the addition of water (50 3 H, CO2CH3), 5.10 (t, J ϭ 7 Hz, 1 H, 5 or 9-H), 5.12 (t, J ϭ 7
ml), the mixture was extracted three times with diethyl ether (100
ml). The combined ethereal extracts were successively washed with
Hz, 1 H, 5 or 9-H), 5.20 (t, J ϭ 7 Hz, 1 H, 13-H), 6.35Ϫ6.50 (m,
1 H, OH), 6.59 (dd, J ϭ 3 Hz, JЈ ϭ 8 Hz, 1 H, 4Ј-H), 6.66 (d, J ϭ
water and brine, dried with Na2SO4, and concentrated in vacuo to 3 Hz, 1 H, 6Ј-H), 6.81 (d, J ϭ 8 Hz, 1 H, 3Ј-H). Ϫ 13C NMR (75.5
give 3.02 g (quantitative) of 53 as a colorless oil; 1H NMR (90 MHz, CDCl3): δ ϭ 15.77, 15.83, 15.9, 16.0, 20.8, 23.3, 26.3, 26.4,
MHz, CDCl3): δ ϭ 0.03 (s, 9 H, SiMe3), 0.27 (s, 9 H, SnMe3), 0.97 28.4, 28.5, 31.8, 33.0, 34.5, 39.4, 39.6, 51.6, 113.50, 113.55, 116.4,
(t, J ϭ 9 Hz, 2 H, CH2Si), 1.50Ϫ2.10 (m, 6 H, THP), 3.40Ϫ4.10 121.2, 121.9, 122.59, 122.63, 123.97, 124.02, 125.1, 125.2, 132.9,
(m, 2 H, THP), 3.71 (br. t, J ϭ 9 Hz, 2 H, CH2CH2Si), 5.15 (s, 2 133.0, 134.36, 134.39, 134.8, 135.0, 136.8, 136.9, 141.86, 141.90,
H, OCH2O), 5.32 (br. s, 1 H, THP), 6.90Ϫ7.10 (m, 3 H, aromatic
153.9, 170.3, 174.5. Ϫ C26H36O5 (428.6): calcd. C 72.87, H 8.47;
H). This compound was employed in the next step without found C 73.06, H 8.58.
further purification.
Methyl (4E,8E)-14-[2Ј-Acetoxy-5Ј-(2Љ,3Љ,4Љ-tri-O-acetyl-1Љ-β--
Methyl (4E,8E)-14-{5Ј-Tetrahydropyranyloxy-2Ј-[2-(trimethyl-
silyl)ethoxymethoxy]phenyl}-4,8,12-trimethyltetradeca-4,8,12-tri-
enoate (54): This was prepared from 53 (3.00 g, 6.16 mmol) and 27
xylopyranosyloxy)phenyl]-4,8,12-trimethyltetradeca-4,8,12-tri-
enoate (58): This was prepared from 57 (400 mg, 0.932 mmol) in
the same manner as described for 25 to give 444 mg of crude 58 as
(1.50 g, 4.10 mmol) in the same manner as described for 36 to give a colorless oil. Ϫ IR (film): ν˜max ϭ 1760 cmϪ1 (s, CϭO), 1590 (w,
2.28 g (92%) of 54 as a yellowish oil; n2D3 ϭ 1.5082. Ϫ IR (film):
CϭC), 1220 (s, CϪO), 1180 (s, CϪO), 1070 (s, CϪO), 1045 (s,
ν˜max ϭ 1740 cmϪ1 (s, CϭO), 1590 (w, CϭC), 1250 (m, SiϪC), 1200 CϪO). This was employed in the next step without further purifi-
1
(s, CϪO), 1155 (m, CϪO), 1080 (s, CϪO). Ϫ H NMR (90 MHz, cation.
CDCl3): δ ϭ 0.03 (s, 9 H, SiMe3), 0.97 (t, J ϭ 9 Hz, 2 H, CH2Si),
(4E,8E)-14-[2Ј-Hydroxy-5Ј-(1Љ-β--xylopyranosyloxy)phenyl]-
1.50Ϫ2.22 (m, 14 H, THP, 6,7,10,11-H2), 1.60 (s, 6 H, 15,16-H3),
4,8,12-trimethyltetradeca-4,8,12-trienoic Acid (9): This was pre-
1.70 (br. s, 3 H, 17-H3), 2.22Ϫ2.43 (m, 4 H, 2,3-H2), 3.30 (d, J ϭ
pared from crude 58 (444 mg) in the same manner as described for
8 Hz, 2 H, 14-H2), 3.40Ϫ4.10 (m, 2 H, THP), 3.66 (s, 3 H,
2 to give 206 mg (44% based on 57) of 9 as a colorless amorphous
CO2CH3), 3.75 (t, J ϭ 9 Hz, 2 H, CH2CH2Si), 5.00Ϫ5.40 (m, 4 H,
solid. Ϫ [α]2D4 ϭ Ϫ16 (c ϭ 0.18, MeOH). Ϫ Rf ϭ 0.65 (iBuOH/
5,9,13-H, THP), 5.17 (s, 2 H, OCH2O), 6.70Ϫ7.10 (m, 3 H, aro-
MeOH/H2O, 8:1:1). Ϫ IR (KBr): ν˜max ϭ 3345 cmϪ1 (s, OϪH), 2930
matic H). Ϫ C35H56O6Si (600.9): calcd. C 69.96, H 9.39; found C
(m), 1700 (m, CϭO), 1655 (m), 1505 (m), 1440 (m), 1375 (w), 1265
70.28, H 9.32.
(w, CϪO), 1200 (m, CϪO), 1100 (m, CϪO), 1075 (m, CϪO), 1040
1
Methyl (4E,8E)-14-(2Ј-Hydroxy-5Ј-tetrahydropyranyloxyphen-
yl)-4,8,12-trimethyltetradeca-4,8,12-trienoate (55): This was pre-
(m, CϪO). Ϫ H NMR (300 MHz, CD3OD): δ ϭ 1.60 (br. s, 6 H,
15,16-H3), 1.70 [s, 5/3 H, 17-H3 (E)], 1.74 [s, 4/3 H, 17-H3 (Z)],
pared from 54 (2.00 g, 3.33 mmol) in the same manner as described 1.90-2.20 (m, 8 H, 6,7,10,11-H2), 2.25 (t, J ϭ 7 Hz, 2 H, 3-H2),
for 22 to give 1.86 g of crude 55 as a brown oil. Ϫ IR (film): ν˜max ϭ
2.35 (br. t, J ϭ 7 Hz, 2 H, 2-H2), 3.22Ϫ3.35 (m, 3 H, 14-H2, 5Љa-
H), 3.39 (t, J ϭ 6 Hz, 1 H, 3Љ-H,), 3.42 (t, J ϭ 6 Hz, 1 H, 2Љ-H),
3435 cmϪ1 (s, OϪH), 1735 (s, CϭO), 1190 (s, CϪO), 1110 (s,
CϪO), 1035 (s, CϪO). Ϫ 1H NMR (90 MHz, CDCl3): δ ϭ 3.50Ϫ3.62 (m, 1 H, 4Љ-H), 3.89 (dd, J ϭ 5 Hz, JЈ ϭ 12 Hz, 1 H,
1.40Ϫ2.25 (m, 14 H, 6,7,10,11-H2, THP), 1.60 (s, 6 H, 15,16-H3), 5Љe-H), 4.62Ϫ4.72 (m, 1 H, 1Љ-H), 5.13 (t, J ϭ 7 Hz, 1 H, 5 or 9-
1.77 (br. s, 3 H, 17-H3), 2.25Ϫ2.45 (m, 4 H, 2,3-H2), 3.32 (d, J ϭ 7 H), 5.15 (t, J ϭ 7 Hz, 1 H, 5 or 9-H), 5.32 (t, J ϭ 7 Hz, 1 H, 13-
Hz, 2 H, 14-H2), 3.40Ϫ4.10 (m, 2 H, THP), 3.64 (s, 3 H, CO2CH3),
4.80Ϫ5.40 (m, 5 H, OH, 5,9,13-H, THP), 6.72Ϫ6.90 (m, 3 H, aro-
H), 6.65 (d, J ϭ 9 Hz, 1 H, 3Ј-H), 6.74 (dd, J ϭ 3 Hz, JЈ ϭ 9 Hz,
1 H, 4Ј-H), 6.81 (br. s, 1 H, 6Ј-H). Ϫ 13C NMR (75.5 MHz,
matic H). This compound was used for the next reaction without CD3OD): δ ϭ 16.08, 16.12, 16.2, 16.3, 23.8, 27.53, 27.57, 27.62,
further purification.
28.9, 29.1, 32.9, 34.5, 35.9, 40.6, 40.8, 66.8, 71.0, 74.7, 77.6, 104.20,
104.23, 115.9, 116.0, 116.3, 119.8, 123.6, 124.2, 125.4, 125.9, 130.0,
130.1, 134.65, 134.69, 135.8, 136.0, 137.0, 137.2, 151.5, 152.0,
178.5. Ϫ MS (70 eV); m/z (%): 504 (1) [Mϩ], 486 (2), 468 (1), 372
(78), 249 (20), 177 (48), 161 (100), 123 (99), 81 (89). Ϫ HRMS:
C28H40O8 [Mϩ]: calcd. 504.2723, found 504.2723. This material is
an inseparable mixture of (12E) and (12Z) isomers (1.3:1).
Methyl (4E,8E)-14-(2Ј-Acetoxy-5Ј-tetrahydropyranyloxyphen-
yl)-4,8,12-trimethyltetradeca-4,8,12-trienoate (56): This was pre-
pared from crude 55 (1.86 g) in the same manner as described for
23 to give 1.32 g (77% based on 54) of 56 as a yellowish oil; nD23
ϭ
1.5169. Ϫ IR (film): ν˜max ϭ 1760 cmϪ1 (s, CϭO), 1740 (s, CϭO),
1210 (s, CϪO), 1190 (s, CϪO), 1180 (s, CϪO), 1125 (m, CϪO),
1040 (m, CϪO). Ϫ 1H NMR (90 MHz, CDCl3): δ ϭ 1.40Ϫ2.15
(m, 14 H, 6,7,10,11-H2, THP), 1.60 (s, 6 H, 15,16-H3), 1.70 [s, 5/3
Methyl (4E,8E)-4,8,12-Ttrimethyl-14-(2Ј,3Ј,4Ј-trimethyl-5Ј-te-
trahydropyranyloxyphenyl)tetradeca-4,8,12-trienoate (60): To
a
H, 17-H3 (E)], 1.75 [d, J ϭ 1 Hz, 4/3 H, 17-H3 (Z)], 2.15Ϫ2.43 (m, stirred and ice-cooled solution of 30 (700 mg, 1.40 mmol) in dry
54 Liebigs Ann./Recueil 1997, 43Ϫ55

Pheromone Synthesis, CLXXXVII
FULL PAPER
pyridine (25 ml) was added trifluoromethanesulfonic anhydride
(592 mg, 2.10 mmol). The stirring was continued for 6 h at room
temperature and for another 1 h after the addition of water (50
4,8,12-trienoate (62): This was prepared from 61 (200 mg, 0.484
mmol) in the same manner as described for 25 to give 197 mg of
crude 62 as a colorless oil. Ϫ IR (film): ν˜max ϭ 1755 cmϪ1 (s, Cϭ
ml). The mixture was extracted three times with diethyl ether (50 O), 1585 (w, CϭC), 1245 (s, CϪO), 1220 (s, CϪO), 1160 (m, CϪO),
ml). The combined ethereal extracts were successively washed with
water, a saturated CuSO4 solution, a saturated NaHCO3 solution
and brine, dried with Na2SO4, and concentrated in vacuo. The resi-
due was purified by chromatography on silica gel (50 g, hexane/
ethyl acetate, 50:1) to give 829 mg of 59 as a yellowish oil. Ϫ IR
(film): ν˜max ϭ 1740 cmϪ1 (s, CϭO), 1575 (w, CϭC), 1245 (m,
SiϪC), 1210 (s, CϪO), 1175 (m, CϪO), 1140 (s, CϪO), 1125 (m,
CϪO), 1085 (m, CϪO), 1040 (m, CϪO). Ϫ 1H NMR (90 MHz,
CDCl3): δ ϭ 1.45Ϫ2.40 (m, 18 H, 2,3,6,7,10,11-H2, THP), 1.60 (s,
6 H, 15,16-H3), 1.70 [s, 9/5 H, 17-H3 (E)], 1.74 [s, 6/5 H, 17-H3
(Z)], 2.18 (s, 3 H, ArCH3), 2.27 (s, 3 H, ArCH3), 3.30Ϫ4.00 (m, 2
H, THP), 3.40 (d, J ϭ 8 Hz, 2 H, 14-H2), 3.64 (s, 3 H, CO2CH3),
5.00Ϫ5.10 (m, 3 H, 5,9,13-H), 5.15 (br. s, 1 H, THP), 6.88 (s, 1 H,
aromatic H). Ϫ To a stirred solution of 59 (700 mg) and tetrameth-
ylstannane (1.18 g 6,59 mmol) in DMF (14 ml) were added lithium
chloride (140 mg, 3.30 mmol) and bis(triphenylphosphane)palladi-
um(II) dichloride (7.7 mg, 0.11 mmol). The stirring was continued
for 12 h at 110°C. The mixture was filtered through a Celite pad
and the Celite was washed with diethyl ether. The ethereal solution
was washed with water and brine, dried with Na2SO4, and concen-
trated in vacuo. The residue was purified by chromatography on
silica gel (50 g, hexane/ethyl acetate, 100:1) to give 409 mg of crude
60 as a colorless oil. Ϫ IR (film): ν˜max ϭ 1740 cmϪ1 (s, CϭO), 1585
(w, CϭC), 1200 (m, CϪO), 1160 (m, CϪO), 1120 (s, CϪO), 1080
(s, CϪO), 1040 (s, CϪO). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ
1.55Ϫ1.75 (m, 3 H, THP), 1.56, 1.58, 1.59, 1.61 (each s, total 6 H,
15,16-H3), 1.79, 1.80 (each s, total 1 H, 17-H3), 1.82Ϫ1.90 (m, 2
H, THP), 1.90Ϫ2.23 (m, 9 H, 6,7,10,11-H2, THP), 2.14, 2.15 (each
s, total 3 H, ArCH3), 2.19 (s, 3 H, ArCH3), 2.28 (br. t, J ϭ 7 Hz,
2 H, 3-H2), 2.35Ϫ2.45 (m, 2 H, 2-H2), 3.29 (d, J ϭ 6 Hz, 2 H, 14-
H2), 3.53Ϫ3.64 (m, 1 H, THP), 3.66 (s, 3 H, CO2CH3), 3.92 (br. t,
J ϭ 9 Hz, 1 H, THP), 5.07Ϫ5.25 (m, 3 H, 5,9,13-H), 5.33, 5.34
(each t, J ϭ 3 Hz, total 1 H, THP), 6.80 [s, 2/5 H, aromatic H (Z)],
6.81 [s, 3/5 H, aromatic H (E)]. This was employed in the next step
without further purification.
1120 (m, CϪO), 1060 (s, CϪO), 1040 (s, CϪO). This was employed
in the next step without further purification.
(4E,8E)-4,8,12-Trimethyl-14-[2Ј,3Ј,4Ј-trimethyl-5Ј-(1Љ-β--xylo-
pyranosyloxy)phenyl]tetradeca-4,8,12-trienoic Acid (10): This was
prepared from crude 62 (197 mg) in the same manner as described
for 2 to give 131 mg (51% based on 61) of 10 as a colorless amorph-
ous solid. Ϫ [α]2D4 ϭ Ϫ12 (c ϭ 0.14, MeOH). Ϫ Rf ϭ 0.64 (iBuOH/
MeOH/H O, 8:1:1). Ϫ IR (KBr): νmax ϭ 3410 cmϪ1 (s, OϪH), 2970
˜
2
(s), 2935 (s), 2905 (s), 1710 (s, CϭO), 1580 (w, CϭC), 1545 (s, Cϭ
C), 1445 (s), 1385 (s), 1305 (m), 1270 (m, CϪO), 1155 (m, CϪO),
1
1075 (s, CϪO), 1050 (s, CϪO), 985 (m), 756 (s). Ϫ H NMR (300
MHz, CD3OD): δ ϭ 1.56, 1.588, 1.593 (each s, total 6 H, 15,16-
H3), 1.70 [s, 9/5 H, 17-H3 (E)], 1.73 [s, 6/5 H, 17-H3 (Z)], 1.90Ϫ2.20
(m, 8 H, 6,7,10,11-H2), 2.10 [s, 9/5 H, 18-H3 (E)], 2.11 [s, 6/5 H,
18-H3 (Z)], 2.15 (s, 3 H, 19-H3), 2.18 (s, 3 H, 20-H3), 2.20Ϫ2.28
(m, 2 H, 3-H2), 2.28Ϫ2.40 (m, 2 H, 2-H2), 3.20Ϫ3.29 (m, 1 H, 5Љa-
H), 3.26 (d, J ϭ 7 Hz, 2 H, 14-H2), 3.39 (t, J ϭ 7 Hz, 1 H, 3Љ-H,),
3.46 (t, J ϭ 7 Hz, 1 H, 2Љ-H), 3.52Ϫ3.64 (m, 1 H, 4Љ-H), 3.89 (dd,
J ϭ 5 Hz, JЈ ϭ 11 Hz, 1 H, 5Љe-H), 4.70 [d, J ϭ 7 Hz, 2/5 H, 1Љ-
H (Z)], 4.72 [d, J ϭ 7 Hz, 3/5 H, 1Љ-H (E)], 5.02Ϫ5.25 (m, 3 H,
5,9,13-H), 6.75 (s, 1 H, 6Ј-H). Ϫ 13C NMR (75.5 MHz, CD3OD):
δ ϭ 12.8, 15.6, 16.11, 16.14, 16.2, 16.4, 16.5, 23.7, 27.4, 27.5, 27.6,
33.0, 33.7, 34.1, 35.3, 36.2, 40.65, 40.73, 66.8, 71.0, 74.8, 77.7,
104.1, 115.5, 115.7, 124.6, 125.0, 125.19, 125.25, 125.3, 125.7,
129.6, 129.7, 134.97, 135.01, 135.8, 136.1, 136.3, 136.9, 137.21,
137.24, 138.6, 154.5, 180.1. Ϫ MS (70 eV); m/z (%): 530 (1) [Mϩ],
512 (1), 503 (1), 476 (1), 398 (68), 203 (98), 149 (100), 81 (49).
Ϫ HRMS: C31H46O7 [Mϩ]: calcd. 530.3244, found 530.3257. This
material is an inseparable mixture of (12E) and (12Z) isomers
(1.5:1).
[1]
R. C. Starr, F. -J. Marner, L. Jaenicke, Proc. Natl. Acad. Sci.
U.S.A. 1995, 92, 641Ϫ645.
[2]
L. Jaenicke, F. -J. Marner, Liebigs Ann. 1995, 1343Ϫ1345.
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L. Jaenicke, R. C. Starr, Eur. J. Biochem. 1996, 241, 581Ϫ585.
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Methyl (4E,8E)-14-(5Ј-Hydroxy-2Ј,3Ј,4Ј-trimethylphenyl)-4,8,12-
trimethyltetradeca-4,8,12-trienoate (61): This was prepared from
crude 60 (350 mg) in the same manner as described for 24 to give
263 mg (63% based on 30) of 61 as a colorless oil; n2D3 ϭ 1.5298.
Ϫ IR (film): ν˜max ϭ 3445 cmϪ1 (s, OϪH), 1740 (s, CϭO), 1720 (s,
CϭO), 1595 (m, CϭC), 1260 (s, CϪO), 1205 (s, CϪO), 1160 (s,
S. Takanashi, K. Mori, Liebigs Ann. 1997, 825Ϫ838.
[5]
S. Takanashi, K. Mori, Liebigs Ann. 1997, 1081Ϫ1084.
[6]
K. Mori, S. Takanashi, Tetrahedron Lett. 1996, 37, 1821Ϫ1824.
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174Ϫ177.
[8]
W. C. Still, C. Gennari, Tetrahedron Lett. 1983, 24, 4405Ϫ4408.
[9]
H. J. Hensel, P. L. Fuchs, Synth. Commun. 1986, 16,
1
1285Ϫ1295.
CϪO), 1080 (s, CϪO). Ϫ H NMR (300 MHz, CDCl3): δ ϭ 1.58,
[10]
M. Mohri, H Kinoshita, K. Inomata, H. Kotake, Chem. Lett.
1,59, 1.61 (each s, total 6 H, 15,16-H3), 1.70 [s, 9/5 H, 17-H3 (E)],
1.72 [d, J ϭ 1 Hz, 6/5 H, 17-H3 (Z)], 1.92Ϫ2.23 (m, 8 H, 6,7,10,11-
H2), 2.13 [s, 9/5 H, 2Ј-CH3 (E)], 2.14 [s, 6/5 H, 2Ј-CH3 (Z)], 2.17
(s, 3 H, 3Ј-CH3), 2.20 (s, 3 H, 4Ј-CH3), 2.23Ϫ2.35 (m, 2 H, 3-H2),
2.35Ϫ2.45 (m, 2 H, 2-H2), 3.26 (d, J ϭ 7 Hz, 2 H, 14-H2), 3.67 (s,
3 H, CO2CH3), 4.77 [s, 3/5 H, OH (E)], 4.88 [s, 2/5 H, OH (Z)],
5.05Ϫ5.30 (m, 3 H, 5,9,13-H), 6.51 (s, 1 H, 6Ј-H). Ϫ C27H40O3
(412.6): calcd. C 78.60, H 9.77; found C 78.36, H 9.69.
1985, 451Ϫ454.
[11]
M. Yamaguchi, A. Horiguchi, A. Fukuda, T. Minami, J. Chem.
Soc., Perkin Trans. 1 1990, 1079Ϫ1082.
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Nauk. S.S.S.R., Ser. Khim. 1989, 2602Ϫ2606.
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D. B. Dess, J. C. Martin, J. Org Chem. 1983, 48, 4156Ϫ4158.
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W.S. Johnson, L. Werthemann, W. R. Bartlett, T. J. Brockson,
T. Li, D. J. Faulkner, M. R. Petersen, J. Am. Chem. Soc. 1970,
92, 741Ϫ743.
[15]
E. J. Corey. D. Y. Gin, R. S. Kania, J. Am. Chem. Soc. 1996,
Methyl (4E,8E)-4,8,12-Trimethyl-14-[2Ј,3Ј,4Ј-trimethyl-5Ј-(2Љ,
3Љ,4Љ-tri-O-acetyl-1Љ-β--xylopyranosyloxy)phenyl]tetradeca-
118, 9202Ϫ9203.
[97222]
Liebigs Ann./Recueil 1997, 43Ϫ55
55