A convenient cross-metathesis approach to trisporins

Article abstract of DOI:10.1016/j.tet.2009.09.074

Three series of trisporins have been prepared using a strategy in which a cross-metathesis is the key step. This reaction has proved to be highly regioselective, allowing the combination of α- or β-ionone derivatives having a 1,1-disustituted olefin with

Full text of DOI:10.1016/j.tet.2009.09.074

Tetrahedron 65 (2009) 9542–9549
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A convenient cross-metathesis approach to trisporins
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Cristobal Lopez-Sanchez, Carmen Hernandez-Cervantes, Antonio Rosales, Mıriam Alvarez-Corral,
*
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Manuel Mun˜oz-Dorado, Ignacio Rodrıguez-Garcıa
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Dpto. de Quımica Organica, Universidad de Almerıa, 04120 Almerıa, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Three series of trisporins have been prepared using a strategy in which a cross-metathesis is the key step.
Received 5 August 2009
Received in revised form
17 September 2009
Accepted 18 September 2009
Available online 22 September 2009
This reaction has proved to be highly regioselective, allowing the combination of a- or b-ionone de-
rivatives having a 1,1-disustituted olefin with trisubstituted alkenes. The stereochemistry of the newly
formed olefins has been established by spectroscopic means.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
β-carotene
R2
Trisporoids are
synthesized from
a
special group of natural products bio-
R3
R4
b
-carotene by several fungi of the order mucor-
ales, like Blakeslea trispora,1–3 Phycomyces blakesleeanus,1,4
Zygorhynchus moelleri3,5 and Mucor mucedo.1,2,6 These fungi are
able to reproduce sexually by zygospores followed by gametangial
fusion. Their sexual development is mediated by hormones
(trisporic acids), but simultaneous and cooperative metabolism in
both mating-types is essential for hormone production: each
mating-type produces prohormones (trisporins, trisporols and
methyl trisporates), which the other can convert into the hormones
(trisporic acids).7 Thus, trisporoids are involved in the recognition
of mating partners, induce the first steps of sexual differentiation
and maintain the development of sexual structures. We are
involved in a multidisciplinary project, which aims to clarify
unknown aspects of the biosynthetic route of trisporic acids from
trisporins
R1
R1
R1
R1
R2
R3
R4
trisporols
CH2OH
R2
R3
R4
methyl trisporates
trisporic acids
CO2Me
R2
b
-carotene (Scheme 1).
Trisporins are located at the first stages of this route,8–11 and are
classified in series according to the functionalization of the side
chain (A, B and C) or the ring (D and E). Natural trisporoids com-
prises both geometric isomers at the C9–C10 double bond,12 while
C7–C8 is always trans. These E/Z isomers show comparable levels of
hormone activity on both the mating types of M mucedo.13
R3
R4
CO2H
The total synthesis of trisporols and methyl trisporates has been
achieved by different strategies, like the cyclization of a linear
precursor,14,15 a cyclization followed by chain extension through
Wittig olefination,16,17 by means of a lactol intermediate,18–23 deg-
Scheme 1. Biogenetic origin of trisporoids.
co-workers27,28 have focused on the preparation of less function-
alized type, the trisporins, using a strategy in which a Pd(0)-cata-
lyzed cross-coupling with organozincates (Knochel coupling) is the
key step.
radation of a enantiomerically pure
a
-hidroxydecalone24,25 and
through Meyer’s chiral bicyclic lactams.26 However only Boland and
Here we present a convenient, high yielding divergent synthesis
able to produce an entire library of trisporins (series A, B and C) to
be screened for the appropriated biological properties (Table 1).
* Corresponding author. Tel.: þ34 950015610; fax: þ34 950015481.
´
´
E-mail address: irodrigu@ual.es (I. Rodrıguez-Garcıa).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.074

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C. Lo´pez-Sanchez et al. / Tetrahedron 65 (2009) 9542–9549
9543
Table 1
Trisporins of series A, B and C
Structure
R1
R2
Compound
Name
Series
–H
–H
–H
]O
]O
]O
–OH
–OH
–OH
–OH
]O
–H
–OH
]O
–H
–OH
]O
–H
1
2
3
4
5
6
7
8
9
4-Dihydrotrisporin A
Trisporin A
4-Desoxytrisporin A
4-Dihydrotrisporin B
Trisporin B
4-Desoxytrisporin B
4-Dihydrotrisporin C
Trisporin C
A
B
R2
C
R1
4-Desoxytrisporin C
2. Results and discussion
2.1. Strategy
K2CO3.35,36 The hydroxyl group was then protected as the t-butyl-
dimethylsilyl ether (12).37 Several methods were assayed for
methylenation of the keto group in 12, from which Wittig reaction
with methylenetriphenyl phosphorane gave the best yield of syn-
thon 13. The second synthon, 15, was prepared by deprotection of
13 with tetrabutylammonium fluoride and oxidation of the allylic
Recently, it has been demonstrated that olefin metathesis has
evolved to be a reliable tool in the synthesis of substituted olefins,
due largely to the advent of powerful ruthenium catalysts that
contain an N-heterocyclic carbene ligand.29–31 Grubbs and co-
workers have proved that the efficiency in olefin cross-metathesis
reactions is affected by the steric bulk of N-heterocyclic carbene
ligands of ruthenium-based catalysts, although for the formation of
trisubstituted olefins the commercial N-mesityl containing catalyst
(25) seems to be the most efficient.31 However, the cross-metath-
esis methodology has not been much used in the field of iso-
prenoids synthesis, although an elegant work in the preparation of
intermediates on the way to tocopherols (vitamin E) has been
published.32 It can also be used to obtain poly-unsaturated systems,
with brilliant but scarce examples of application of this reaction to
the chemo- and stereoselective synthesis of conjugated 1,3,5-triene
moieties contained in bioactive natural products.33,34 However, to
the best of our knowledge, there are no examples of application to
the preparation of conjugated trienes when both terminus olefins
have a high degree of substitution. Here we present an application
of this reaction to the preparation of the trisporin family of natural
products. Our approach follows the retrosynthetic analysis depic-
ted in Scheme 2.
alcohol (14)38,39 with MnO2. A similar Wittig olefination of
b-ion-
one led to the formation of the third synthon 16.39 Chain side
precursors are commercial (17, 18) or readily accessible by standard
procedures (19).40
We first tried to perform the cross-metathesis coupling between
compound 13 and 1-hexene using Grubbs second generation cata-
lyst (25), but only the dimerization product of the monosubstituted
olefin (5-decene) was obtained. Fortunately, the use of the tri-
substituted olefin 17, much less reactive towards the ruthenium
catalyst, avoided this problem, and 20 was formed in excellent yield
as a 2.7:1 mixture of E:Z stereoisomers, which could not be separated
by column chromatography. Deprotection of the TBS group using
TBAF allowed us to obtain 4-dihydrotrisporin A, (1).28 Table 2 shows
the results obtained for all the other possible combinations, which
behaved similarly in the cross-metathesis reaction, although the
yields were significantly lower for those having a carbonyl group at
C-4, specially when it is conjugated with the triene system (products
formed from compound 15). Despite of this, global yield of trisporins
from commercial starting materials can be considered good or, in
some cases, excellent, as a result of the synthetic design (Table 2).
Small amount of E:Z mixtures of 7, 21 and 23 could be separated
by meticulous column chromatography and both stereoisomers
could be characterized spectroscopically in each case. Detailed
analysis of the NOESY spectrum of the minor isomer of 21 allowed
us to establish unambiguously the stereochemistry of the C9 dou-
ble bond as Z (Fig. 1). The most significant differences between the
1H NMR of the two isomers are the chemical shifts of the three
olefinic protons. H7 and H8 signals are significantly deshielded in
the Z isomer with respect to those in the E isomer. Thus, in the Z
isomer H-8 appears as a doublet at 6.42 ppm (J¼16.6 Hz) and H-7 at
6.10 ppm (J¼16.6 Hz) while in the E isomer H-8 appears as a dou-
blet at 6.02 ppm (J¼16.6 Hz) and H-7 at 5.94 ppm (J¼16.6 Hz). It is
also interesting to highlight H-10, which appears as a broad triplet
R2
R1
17
5
3
2
4
1
8
10
12
14
R1
R2
6
7
9
11 13
α-ionone
15 16
18
β-ionone
Scheme 2. Retrosynthesis of trisporins from
a
- and
b
-ionone through cross-metathesis.
in both cases, but at lower field for the E isomer (E:
d
¼5.37 ppm,
The disconnection of the D9 double bond of the trisporin skel-
eton needs, if a cross-metathesis has to be performed, a simple
olefin for the side chain terminus, and a triene, which can be readily
J¼6.1 Hz; Z: ¼5.31 ppm, J¼6.9 Hz). These data are in agreement
d
with previous discussions on the stereochemistry of cis and trans
isomers of trisporic acid C, proposed on the basis of the chemical
shifts of their olefinic protons.14 These results can be extended to
the other trisporin mixtures prepared by us, and constitute a gen-
eral method for a fast elucidation of the C9 double bond geometry
in trisporoids. Tentative assignations previously published should
be reconsidered at the light of this information.
prepared from a- or b-ionone, as simpler synthons.
2.2. Synthetic approach
The preparation of the cross-metathesis reactants is summa-
rized in Scheme 3. Ring side synthons were prepared from
a- and
b
-ionone as commercial starting materials. -Ionone was regiose-
a
3. Conclusion
lectively epoxidised using m-chloroperbenzoic acid, and the
resulting epoxide (10) was isomerised to the corresponding
hydroxyionone derivative (11) by treatment with methanolic
Nine trisporins have been prepared through a divergent strategy
in which the key step is a cross-metathesis catalyzed by the Grubbs

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C. Lo´pez-Sanchez et al. / Tetrahedron 65 (2009) 9542–9549
OTBS
a
O
CH2
17
13
α-ionone
O
b
5
3
2
4
N
Cl
Cl
N
Mes
Mes
10
CH2
8
9
6
Ru
7
1
Ph
O
P(Cy)3
18
15
25
c
R1
O
CH2
17
5
6
19
3
2
4
OTBS
8
10 12
14
R2
16
9
β-ionone
7
11 13
1
15
16
18
TRISPORINS
Scheme 3. Reagents and conditions: (a) i: m-CPBA, DCM, 0 ꢀC, 78% of 10; ii: K2CO3, MeOH,
D
, 95% of 11; iii: TBSCl, DMF, 50 ꢀC, 70% of 12; iv: Ph3PCH3Br, n-BuLi, ꢂ35 ꢀC, THF, 76% of
13. (b) i: n-Bu4NF, THF, 97% of 14; ii: MnO2, n-hexane,
D
, 95% of 15. (c) Ph3PCH3Br, n-BuLi, ꢂ35 ꢀC, THF, 65% of 16.
second generation ruthenium complex (25). The process can be
extended to the preparation of other trisporoids with different
substitution patterns on the ring or chain. Although the stereo-
selectivity of the reaction was moderate to low, in some cases both
E and Z isomers could be isolated and identified thoroughly using
several NMR techniques.
Spectral properties were in agreement with those previously
reported.37
4.3. Methylenation of ketones
4.3.1. General Wittig reaction procedure. Methyl-triphenylphos-
phonium bromide (1.5 equiv) was suspended in dry THF (2 mL/
mmol), under nitrogen, and cooled to ꢂ35 ꢀC. n-BuLi (1.6 M in
hexane,1.5 equiv) was slowly added and the suspension was stirred
until an orange colour appeared (30 min approx.). Then, a solution
of the ketone (1 equiv) in dry THF (1 mL/mmol) was slowly added
and the reaction mixture was allowed to warm to room tempera-
ture and stirred for 12 h. The solution was diluted with Et2O and
washed with brine. The organic layer was dried over MgSO4, fil-
tered and the solvent removed under reduced pressure. Purification
was achieved on silica gel column chromatography using hex-
ane:Et2O (95:5) for elution.
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded on a Bruker Avance DPX
300 or Avance DRX 500 spectrometer. Chemical shifts are given in
ppm relative to TMS. 13C NMR peak assignments were made with
the aid of 2D NMR (HMBC, HMQC and NOESY). Infrared spectra
were recorded in liquid film between NaCl plates on an FTIR
Mattson Genesis II spectrometer, and mass spectra were performed
on a AutoSpec-Q VG-Analitical (Fisons) (HRMS) instrument, using
the Fast Atom Bomb technique (FAB) with a 1% NaI doped matrix of
thioglycerol or glycerol.
4.3.2. Compound 13. Following the general procedure, phospho-
nium salt (1.1 g, 3.2 mmol), n-BuLi (2 mL, 3.2 mmol), 12 (795 mg,
2.5 mmol) and THF (10 mL), afforded 13 (595 mg, 1.9 mmol, 76%
a- and b-ionone were purchased to Acros, [1,3-bis(2,4,6-trime-
yield). Oil, IR
n
(cmꢂ1) 2954, 2931, 2856, 1468, 1359, 1253; 1081,
thylphenyl)-2-imidazolidinylidene]dichloro(phenylmethylene)(tri-
cyclo-hexylphosphine)ruthenium (Grubbs second generation
catalyst) (25), 2-methyl-2-heptene (17) and 6-methyl-5-hepten-2-
one (18) were purchased to Sigma–Aldrich, and 6-methyl-5-
hepten-2-ol41 and its t-butyldimethylsilyl derivative (19)40 were
prepared following literature procedures.
1048, 853, 773; HRFABMS (m/z): calcd (C20H36OSiNa): 343.2433,
found: 343.2428 [MþNa]þ; 1H NMR (300 MHz, CDCl3)
d (ppm) 6.16
(1H, d, J¼16.5 Hz, H-8), 6.06 (1H, d, J¼16.5 Hz, H-7), 4.96 (2H, bs, H-
10), 4.05 (1H, t, J¼5.3 Hz, H-4), 1.92 (3H, s, H-14)*, 1.83 (1H, m), 1.76
(3H, s, H-13)*, 1.67 (2H, m), 1.41 (1H, m), 1.06 (3H, s, H-11), 1.01 (3H,
s, H-12), 0.94 (9H, s, SiC(CH3)3), 0.12 (6H, s, Si(CH3)2); 13C NMR
4.2. Synthesis of compound 12
(75 MHz, CDCl3) d
(ppm) 142.23 (C, C-6)#, 139.89 (C, C-9)#, 136.42
(CH, C-8), 130.99 (C, C-5), 127.15 (CH, C-7), 115.36 (CH2, C-10), 71.16
(CH, C-4), 35.26 (C, C-1), 34.59 (CH2, C-2), 29.25 (CH2, C-3), 28.40
(CH3, C-11), 28.30 (CH3, C-12), 25.90 (CH3, SiC(CH3)3), 18.35 (CH3, C-
14)*, 18.44 (CH3, C-13)*, 18.14 (C, SiC(CH3)3), ꢂ4.66 (CH3, Si(CH3)),
ꢂ4.25 (CH3, Si(CH3)). *,# may be interchanged.
Imidazole (4.1 g, 60 mmol) and TBSCl (4.3 g, 29 mmol) were
added to a solution of 4-(3-hydroxy-2,6,6-trimethylcyclohex-1-
enyl)but-3-en-2-one (11)35,36 (5 g, 24 mmol) in DMF (15 mL). The
mixture was stirred for 6 h at 50 ꢀC and then, was poured on cold
hexane (23 mL). The layers were separated and the DMF one was
washed with hexane (23 mLꢁ2) and Et2O (23 mL). The unified
hexane and ether extracts were washed with brine, dried over
MgSO4, filtered and the solvent was removed in vacuo. The residue
was purified by flash chromatography (hexane:Et2O, 98:2) and (E)-
4-(3-(tert-butyldimethylsilyloxy)-2,6,6-trimethylcyclohex-1-enyl)-
but-3-en-2-one (12) (5.4 g, 16.8 mmol, 70% yield) was obtained.
4.3.3. Compound 16. Following the general procedure, phospho-
nium salt (10 g, 28 mmol), n-BuLi (12 mL, 28 mmol,),
(3.6 g, 18.7 mmol) and THF (84 mL), afforded 16 (3 g, 15.8 mmol,
84% yield). Oil, IR
(cmꢂ1) 2962, 2927, 2864, 1603, 1451, 967;
b-ionone
n
HRFABMS (m/z): calcd (C14H22Na): 213.1619, found: 213.1601
[MþNa]þ; 1H NMR (300 MHz, CDCl3)
d (ppm) 6.13 (2H, bs, H-7,

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C. Lo´pez-Sanchez et al. / Tetrahedron 65 (2009) 9542–9549
9545
Table 2
Cross-metathesis and global yields in the synthesis of trisporins of series A, B and C
Series
Ring synthon
Chain synthon
Cross-metathesis product
Cross-metathesisa (%)
E:Zb
Trisporinc (%)
OTBS
13
17
20 (95%)
2.7:1
4-Dihydrotrisporin A, 1 (33%)
O
A
15
16
17
17
2 (69%)
3 (95%)
3.4:1
1.8:1
Trisporin A, 2 (24%)
4-Desoxytrisporin A, 3 (80%)
OTBS
13
15
18
18
21 (70%)
5 (57%)
2.5:1
1.8:1
4-Dihydrotrisporin B, 4 (20%)
O
O
B
Trisporin B, 5 (20%)
O
16
13
18
19
6 (75%)
1.2:1
3.2:1
4-Desoxytrisporin B, 6 (65%)
4-Dihydrotrisporin C, 7 (16%)
O
OTBS
22 (75%)
OTBS
O
C
15
16
19
19
23 (89%)
24 (75%)
3.2:1
1.8:1
Trisporin C, 8 (10%)
OTBS
OTBS
4-Desoxytrisporin C, 9 (80%)
a
Cross-metathesis yield.
E:Z ratio determined by 1H NMR analysis.
Trisporin global yield from commercial starting materials.
b
c
H-8), 4.95(2H, bs, H-10), 2.03(2H, t, J¼6.3 Hz, H-4),1.93 (3H, s, H-14)*,
signals as previously reported.39 HRFABMS (m/z): calcd (C14H20ONa):
1.73 (3H, s, H-13)*, 1.65 (2H, m), 1.49 (2H, m), 1.04 (6H, s, H-11,
227.1412, found: 227.1437 [MþNa]þ;1H NMR (300 MHz, CDCl3)
d(ppm)
H-12); 13C NMR (75 MHz, CDCl3):
d
(ppm) 142.44 (C, C-9), 137.43
6.25 (1H, d, J¼16.2 Hz, H-8), 6.12 (1H, d, J¼16.2 Hz, H-7), 5.06 (1H, s, H-
10a), 5.03 (1H, s, H-10b), 2.46 (2H, t, J¼6.5 Hz, H-3), 1.89 (3H, s H-13),
1.82 (2H, t, J¼6.5 Hz, H-2),1.79 (3H, s, H-14),1.14 (6H, s, H-11, H-12); 13C
(C, C-6), 135.76 (CH, C-8), 128.93 (C, C-5), 127.44 (CH, C-7), 114.81
(CH2, C-10), 39.47 (CH2, C-2), 34.11 (C, C-1), 32.85 (CH2, C-3), 28.82
(CH3, C-11, C-12), 21.56 (CH3, C-13)*, 19.23 (CH2, C-4), 18.49 (CH3,
C-14)*. * may be interchanged.
NMR (75 MHz, CDCl3) d (ppm) 199.14 (C, C-4),160.90 (C, C-6),141.34 (C,
C-9), 138.65 (CH, C-8), 129.82 (C, C-5), 125.23 (CH, C-7), 118.49 (CH2,
C-10), 37.22 (CH2, C-2), 35.53 (C, C-1), 34.19 (CH2, C-3), 27.39 (CH3, C-11,
C-12), 18.15 (CH3, C-14), 13.53 (CH3, C-13).
4.4. Synthesis of compound 15
MnO2 (845 mg, 9.71 mmol) was added to a solution of (E)-2,4,4-
trimethyl-3-(3-methylbuta-1,3-dienyl)-2-cyclohexen-ol (14) (500 mg,
2.43 mmol) in hexane (20 mL). The mixture was refluxed for 2 h, and
then was filtered over Celite using CH2Cl2 for washing. After removal of
the solvent, 15 was obtained as an oil (471 mg, 2.31 mmol, 95%). IR
4.5. Cross-metathesis
4.5.1. General cross metathesis procedure. To a solution of chain side
synthon (17, 18 or 19) (1.5 to 2 equiv) in dry CH2Cl2 (1 mL/mmol)

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C. Lo´pez-Sanchez et al. / Tetrahedron 65 (2009) 9542–9549
9546
H-8
H-7
H-10
ppm
1.0
1.2
1.4
1.6
1.8
2.0
2.2
2.4
2.6
2.8
CH3-17
CH3-18
TBSO
1.75
Me
6.42
Me
H
2.50
H
O
CH2-11
5.32
H
1.86
6.10
ppm
6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4 5.3
Figure 1. Diagnostic correlations originated by olefinic protons in the 2D-NOESY spectrum of Z-21.
under nitrogen atmosphere, Grubbs second generation catalyst
(1/3 portion of a total of 5% mol) was added. The solution was
heated to 35 ꢀC and then, a solution of ring side synthon (13, 15 or
16) (1 equiv) in dry CH2Cl2 (1 mL/mmol) was added. The mixture
was heated to reflux for 6 h, and another portion (1/3) of the cat-
alyst was added. After six more hours, the last portion of catalyst
was added, and the mixture was heated to reflux for an additional
period of 6 h. After cooling to room temperature, solvent was re-
moved under reduced pressure, and the resulting crude oil was
purified by silica gel column chromatography.
(6H, s, H-15, H-16); (signals due to the Z isomer) d (ppm) 6.46 (1H, d,
J¼16.2 Hz, H-8), 6.14–6.03 (1H, m, H-7), 5.37 (1H, t, J¼7.7 Hz, H-10),
1.90 (3H, bs, H-17)#, 1.76 (3H, bs, H-18)#, 1.07 (6H, s, H-15, H-16);
(common signals)
H-4), 1.66 (2H, m), 1.51 (2H, m), 1.40 (4H, m), 0.95 (3H, m, H-14); 13C
NMR (CDCl3, 75 MHz) (signals due to the E isomer) (ppm) 138.04
d
(ppm) 2.19 (2H, m, H-11), 2.04 (2H, t, J¼6.1 Hz,
d
(CH, C-8),137.86 (C, C-6), 133.82 (C, C-9), 131.47 (CH, C-10), 128.10
(C, C-5), 123.92 (CH, C-7), 34.09 (C, C-1), 32.88 (CH2, C-12), 31.90
(CH2, C-4), 28.00 (CH2, C-11), 22.46 (CH2, C-13), 21.62 (CH3, C-17),
12.22 (CH3, C-18); (signals due to the Z isomer) d (ppm) 138.21 (C, C-6),
132.27 (C, C-9), 130.40 (CH, C-8), 129.70 (CH, C-10), 128.49 (C, C-5),
126.67 (CH, C-7), 34.16 (C, C-1), 32.92 (CH2, C-12), 32.29 (CH2, C-4),
27.04 (CH2, C-11), 22.31 (CH2, C-13), 21.65 (CH3, C-17)*, 20.43
4.5.2. Trisporin A (2). Starting from 17 (0.3 mL, 2.06 mmol), ru-
thenium catalyst 25 (42 mg, 0.049 mmol), 15 (200 mg, 0.98 mmol),
CH2Cl2 (3 mL) and following the general procedure (chromatogra-
phy eluent hexane:Et2O 95:5), 2 was obtained as an oil (176 mg,
0.68 mmol, 69% yield as a mixture E/Z 3.4:1). IR and HRMS signals
as previously reported.28 1H NMR (CDCl3, 300 MHz) (signals due to
(CH3, C-18)*; (common signals) d (ppm) 39.55 (CH2, C-2), 28.87 (CH3,
C-15, C-16), 19.31 (CH2, C-3), 13.99 (CH3, C-14). *,# may be
interchanged.
the E isomer)
J¼16.2 Hz, H-7), 5.57 (1H, t, J¼7.3 Hz, H-10); (signals due to the Z
isomer)
(ppm) 6.63 (1H, d, J¼16.2 Hz, H-8), 6.15 (1H, d, J¼16.2 Hz,
(ppm) 2.49
d
(ppm) 6.22 (1H, d, J¼16.2 Hz, H-8), 6.05 (1H, d,
4.5.4. TBS-derivative of 4-dihydrotrisporin A (20). Starting from 17
(0.1 mL, 0.66 mmol), ruthenium catalyst 25 (13 mg, 0.016 mmol),13
(100 mg, 0.31 mmol), CH2Cl2 (1 mL) and following the general
procedure (chromatography eluent hexane:Et2O 98:2), 20 was
obtained as an oil (111 mg, 0.29 mmol, 95% yield as a mixture E/Z
d
H-7), 5.52 (1H, t, J¼7.3 Hz, H-10); (common signals)
d
(2H, m, H-3), 2.16 (2H, m, H-11), 1.83 (3H, bs, H-17)*, 1.81 (3H, bs, H-
18)*, 1.38 (6H, m, H-2, H-12, H-13), 1.16 (6H, s, H-15, H-16), 0.91 (3H,
t, J¼7.3 Hz, H-14); 13C NMR (CDCl3, 75 MHz) (signals due to the E
2.7:1). IR
n
(cmꢂ1) 2957, 2931, 2858, 1719, 1672, 1463, 1361, 1256,
1083, 837, 777. HRFABMS (m/z): calcd (C24H44OSiNa): 399.3059,
isomer)
d (ppm) 199.28 (C, C-4), 161.70 (C, C-6), 141.34 (CH, C-8),
found: 399.3051 [MþNa]þ; 1H NMR (CDCl3, 300 MHz) (signals due
135.82 (CH, C-10), 133.47 (C, C-9), 129.33 (C, C-5), 121.85 (CH, C-7),
27.47 (CH3, C-15, C-16); (signals due to the Z isomer) (ppm) 140.24
(CH, C-8), 133.42 (CH, C-10), 124.45 (CH, C-7), 27.20 (CH3, C-15, C-
16); (common signals) (ppm) 37.23 (CH2, C-2), 35.42 (C, C-1), 34.18
to the E isomer)
d
(ppm) 6.06 (1H, d, J¼16.1 Hz, H-8), 5.96 (1H, d,
d
J¼16.1 Hz, H-7), 5.46 (1H, t, J¼7.3 Hz, H-10), 1.80 (3H, s, H-17)*; 1.75
(3H, s, H-18)*, (signals due to the Z isomer) (ppm) 6.46 (1H, d,
J¼16.1 Hz, H-8), 6.06 (1H, d, J¼16.1 Hz, H-7), 5.36 (1H, t, J¼7.3 Hz, H-
10),1.87 (3H, s, H-17)#, 1.77 (3H, s, H-18)#, (common signals)
(ppm)
d
d
(CH2, C-3), 31.50 (CH2, C-12), 28.13 (CH2, C-11), 22.34 (CH2, C-13),
13.88 (CH3, C-14), 13.64 (CH3, C-17)*, 12.00 (CH3, C-18)*. * may be
interchanged.
d
4.06 (1H, t, J¼5.6 Hz, H-4), 2.16 (2H, m, H-11), 1.67 (2H, m, H-3), 1.37
(6H, m, H-2, H-12, H-13), 1.05 (3H, s, H-15), 1.01 (3H, s, H-16), 0.95
(3H, t, J¼6.1 Hz, H-14), 0.93 (9H, s, SiC(CH3)3), 0.10 (6H, s, Si(CH3)2);
4.5.3. 4-Desoxytrisporin A (3). Starting from 17 (0.3 mL, 2.21 mmol),
ruthenium catalyst 25 (45 mg, 0.053 mmol), 16 (200 mg, 1.05
mmol), CH2Cl2 (3 mL) and following the general procedure (chro-
matography eluent hexane:Et2O 98:2), 3 was obtained as an oil
13C NMR (CDCl3, 75 MHz) (signals due to the E isomer)
d (ppm)
140.35 (C, C-6), 138.65 (CH, C-8), 133.67 (C, C-9), 132.12 (CH, C-10),
130.66 (C, C-5), 123.59 (CH, C-7), 31.82 (CH2, C-12), 28.36 (CH2, C-
11), 18.43 (CH3, C-17)#, 12.21 (CH3, C-18)#; (signals due to the Z
(245 mg, 0.99 mmol, 95% yield as a mixture E/Z 1.8:1). IR
n
(cmꢂ1
)
isomer)
7), 32.22 (CH2, C-12), 27.99 (CH2, C-11), 20.40 (CH3, C-17)*, 13.98
(CH3, C-18)*; (common signals) (ppm) 71.29 (CH, C-4), 35.28 (CH2,
d (ppm) 131.01 (CH, C-8), 130.34 (CH, C-10), 126.40 (CH, C-
2958, 2926, 2862, 1455, 966; HRFABMS (m/z): calcd (C18H30Na):
269.2245, found: 269.2256 [MþNa]þ; 1H NMR (CDCl3, 300 MHz)
d
(signals due to the E isomer)
d
(ppm) 6.14–6.03 (2H, m, H-7, H-8), 5.46
C-2), 34.63 (C, C-1), 29.28 (CH2, C-3), 28.43 (CH3, C-15, C-16), 25.92
(1H, t, J¼6.5 Hz, H-10), 1.83 (3H, bs, H-17)*, 1.74 (3H, bs, H-18)*, 1.06
(CH3, (CH3)3CSi), 22.42 (CH2, C-13), 18.16 (C, (CH3)3CSi), 13.98 (CH3,

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C. Lo´pez-Sanchez et al. / Tetrahedron 65 (2009) 9542–9549
9547
C-14), ꢂ4.25 (CH3, (CH3)2Si), ꢂ4.64 (CH3, (CH3)2Si).*,# may be
(2H, m, H-3), 1.05 (3H, s, H-15), 0.99 (3H, s, H-16), 0.93 (9H, s,
SiC(CH3)3), 0.11 (6H, s, Si(CH3)2); 13C NMR (CDCl3,125 MHz)
(ppm)
interchanged.
d
208.39 (C, C-13), 140.51 (C, C-6), 133.35 (C, C-9), 130.98 (C, C-5),
130.43 (CH, C-8), 127.57 (CH, C-7, C-10), 71.27 (CH, C-4), 43.95 (CH2,
C-12), 35.34 (CH2, C-2), 34.63 (C, C-1), 30.90 (CH3, C-14), 29.32 (CH2,
C-3), 28.45 (CH3, C-15, C-16), 25.97 (CH3, (CH3)3CSi), 21.81 (CH2, C-
11), 20.37 (CH3, C-18), 18.41 (CH3, C-17), 18.22 (CH3, (CH3)3CSi),
ꢂ4.21 (CH3, (CH3)2Si), ꢂ4.59 (CH3, (CH3)2Si).
4.5.5. Trisporin B (5). Starting from 18 (0.10 mL, 0.84 mmol), ru-
thenium catalyst 25 (17 mg, 0.02 mmol), 15 (76 mg, 0.40 mmol),
CH2Cl2 (2 mL) and following the general procedure (chromatogra-
phy eluent hexane:Et2O 8:2), 5 was obtained as an oil (59 mg,
0.22 mmol, 57% yield as a mixture E/Z 1.8:1). IR and HRMS signals as
previously reported.28 1H NMR (CDCl3, 300 MHz) (signals due to the
E isomer)
J¼16.4 Hz, H-7), 5.47 (1H, t, J¼7.2 Hz, H-10), 2.12 (3H, s, H-14), 1.12
(6H, s, H-15, H-16); (signals due to the Z isomer) (ppm) 6.58 (1H, d,
d
(ppm) 6.15 (1H, d, J¼16.3 Hz, H-8), 6.05 (1H, d,
4.5.7.2. (E). 1H NMR (CDCl3, 300 MHz)
d (ppm) 6.02 (1H, d,
J¼16.6 Hz, H-8), 5.94 (1H, d, J¼16.6 Hz, H-7), 5.37 (1H, t, J¼6.1 Hz,
H-10), 4.03 (1H, m, H-4), 2.55–2.39 (4H, m, H-11, H-12), 2.16 (3H, s,
H-14), 1.78 (3H, s, H-17)*, 1.72 (3H, s, H-18)*; 1.42 (4H, m, H-2, H-3),
1.04 (3H, s, H-15), 0.98 (3H, s, H-16), 0.97 (9H, s, SiC(CH3)3), 0.09
d
J¼16.2 Hz, H-8), 6.15 (1H, d, J¼16.3 Hz, H-7), 5.41 (1H, t, J¼7.2 Hz, H-
10), 2.09 (3H, s, H-14), 1.14 (6H, s, H-15, H-16); (common signals)
d
(ppm) 2.46 (6H, m, H-3, H-11, H-12),1.82 (2H, m, H-2),1.79 (3H, bs,
H-18), 1.77 (3H, bs, H-17); 13C NMR (CDCl3, 75 MHz) (signals due to
the E isomer) (ppm) 207.79 (C, C-13), 199.20 (C, C-4), 161.46 (C, C-
(6H, s, Si(CH3)2). 13C NMR (CDCl3, 75 MHz)
d (ppm) 208.26 (C, C-13),
140.17 (C, C-6), 138.10 (CH, C-8), 134.82 (C, C-9), 130.54 (C, C-5),
129.37 (CH, C-10), 124.51 (CH, C-7), 71.22 (CH, C-4), 43.34 (CH2, C-
12), 35.24 (CH2, C-2), 34.60 (C, C-1), 29.90 (CH3, C-14), 29.24 (CH2,
C-3), 28.38 (CH3, C-15, C-16), 25.90 (CH3, (CH3)3CSi), 22.55 (CH2, C-
11), 18.39 (CH3, C-17), 12.18 (CH3, C-18), 18.13 (CH3, (CH3)3CSi),
ꢂ4.26 (CH3, (CH3)2Si), ꢂ4.66 (CH3, (CH3)2Si). * may be interchanged.
d
6), 140.67 (CH, C-8), 134.23 (C, C-9), 133.10 (CH, C-10), 129.48
(C, C-5), 122.68 (CH, C-7), 42.92 (CH2, C-12), 35.58 (C, C-1), 29.85
(CH3, C-14), 22.60 (CH2, C-11), 13.63 (CH3, C-17), 12.01 (CH3, C-18);
(signals due to the Z isomer) d (ppm) 207.71 (C, C-13), 199.13 (C, C-4),
161.42 (C, C-6), 132.63 (CH, C-8), 132.45 (C, C-9), 130.88 (CH, C-10),
129.69 (C, C-5), 125.41 (CH, C-7), 43.45 (CH2, C-12), 35.53 (C, C-1),
29.83 (CH3, C-14), 21.67 (CH2, C-11), 20.03 (CH3, C-18)*, 13.59 (CH3,
C-17)*; (common signals) d (ppm) 37.24 (CH2, C-2), 34.18 (CH2, C-3),
27.45 (CH3, C-15, C-16). * may be interchanged.
4.5.8. TBS-derivative of 4-dihydrotrisporin C (22). Starting from 19
(113 mg, 0.47 mmol), ruthenium catalyst 25 (13 mg, 0.016 mmol),
13 (100 mg, 0.31 mmol), CH2Cl2 (0.8 mL) and following the general
procedure (chromatography eluent hexane:Et2O 99:1), 22 was
obtained as an oil (118 mg, 0.23 mmol, 75% yield as a mixture E/Z
3.2:1). HRFABMS (m/z): calcd (C30H58O2SiNa): 529.3873, found:
529.3832 [MþNa]þ; 1H NMR (CDCl3, 300 MHz) (signals due to the E
4.5.6. 4-Desoxytrisporin B (6). Starting from 18 (0.3 mL, 2.21 mmol),
ruthenium catalyst 25 (45 mg, 0.053 mmol), 16 (200 mg, 1.05 mmol),
CH2Cl2 (3 mL) and following the general procedure (chromatography
eluent hexane:Et2O 85:15), 6 was obtained as an oil (75% yield as
isomer)
d (ppm) 1.80 (3H, s, H-17)*, 1.74 (3H, s, H-18)*, 1.15 (3H, d,
J¼6.1 Hz, H-14); (signals due to the Z isomer)
d (ppm) 6.43 (1H, dd,
a mixture E/Z 1.2:1). IR
n
(cmꢂ1) 2928, 2865, 1716, 1454, 1359, 968;
J¼16.2 Hz, J¼4.0 Hz, H-8),1.85 (3H, s, H-17)#,1.84 (3H, s, H-18)#,1.14
HRFABMS (m/z): calcd (C18H28ONa): 283.2038, found: 283.2061
[MþNa]þ; 1H NMR (CDCl3, 300 MHz) (signals due to the E isomer)
(3H, d, J¼6.4 Hz, H-14); (common signals)
d (ppm) 6.09–5.93 (3H, m,
H-7 (Z), H-7 (E), H-8 (E)), 5.14 (1H, m, H-10), 4.04 (1H, m, H-4), 3.86
(1H, m, H-13), 2.30 (2H, m), 2.20 (2H, m), 1.86 (2H, m), 1.45 (2H, m),
1.04 (3H, s, H-15), 1.00 (3H, s, H-16), 0.93 (9H, s, (CH3)3CSi), 0.09
(6H, s, (CH3)2Si). *,# may be interchanged.
d
(ppm) 5.96 (2H, bs, H-7, H-8), 5.37 (1H, t, J¼7.3 Hz, H-10), 2.13 (3H,
s, H-14), 1.78 (3H, bs, H-18), 1.66 (3H, bs, H-17), 0.98 (6H, bs, H-15, H-
16); (signals due to the Z isomer)
d
(ppm) 6.36 (1H, d, J¼16.2 Hz, H-8),
6.09 (1H, d, J¼16.2 Hz, H-7), 5.24 (1H, t, J¼7.2 Hz, H-10), 2.11 (3H, s,
H-14), 1.82 (3H, bs, H-18), 1.69 (3H, bs, H-17), 0.99 (6H, bs, H-15, H-
4.5.9. TBS-derivative of trisporin C (23). Starting from 19 (249 mg,
1.03 mmol), ruthenium catalyst 25 (21 mg, 0.024 mmol), 15
(100 mg, 0.49 mmol), CH2Cl2 (1.5 mL) and following the general
procedure (chromatography eluent hexane:Et2O 95:5), 23 was
obtained as an oil (170 mg, 0.44 mmol, 89% yield as a mixture E/Z
16); (common signals)
1.99 (2H, m, H-4), 1.59 (2H, m, H-3), 1.44 (2H, m, H-2); 13C NMR
(CDCl3, 75 MHz) (signals due to the E isomer) (ppm) 208.18 (C, C-13),
d (ppm) 2.49 (2H, m, H-12), 2.41 (2H, m, H-11),
d
137.63 (C, C-6), 137.44 (CH, C-8), 134.92 (C, C-9), 128.72 (CH, C-10),
128.30 (C, C-5), 124.76 (CH, C-7), 43.34 (CH2, C-12), 39.40 (CH2, C-2),
34.04 (C, C-1), 22.53 (CH2, C-11), 21.55 (CH3, C-17), 12.17 (CH3, C-18);
3.2:1). IR
n
(cmꢂ1) 2958, 2928, 2857, 1728, 1670, 1462, 1375, 1256,
1031, 835, 774. HRFABMS (m/z): calcd (C24H42O2SiNa): 413.2852,
found: 413.2876 [MþNa]þ; A small amount of this mixture was
rechromatographied and both isomers were isolated.
(signals due to the Z isomer) d (ppm) 208.26 (C, C-13), 137.98 (C, C-6),
133.37 (C, C-9), 129.78 (CH, C-8), 128.77 (C, C-5), 127.63 (CH, C-7),
126.93 (CH, C-10), 43.85 (CH2, C-12), 39.44 (CH2, C-2), 34.08 (C, C-1),
21.68 (CH2, C-11), 21.61 (CH3, C-17), 20.33 (CH3, C-18); (common
4.5.9.1. (Z). 1H NMR (CDCl3, 300 MHz)
d (ppm) 6.65 (1H, d,
signals)
C-16), 19.21 (CH2, C-3).
d
(ppm) 32.80 (CH2, C-4), 29.84 (CH3, C-14), 28.80 (CH3, C-15,
J¼16.2 Hz, H-8), 6.18 (1H, d, J¼16.3 Hz, H-7), 5.54 (1H, t, J¼7.6 Hz, H-
10), 3.81 (1H, sext, J¼6.1 Hz, H-13), 2.53 (2H, t, J¼6.6 Hz, H-3), 2.28
(1H, m, H-11a), 2.19 (1H, m, H-11b),1.90 (3H, bs, H-18)*,1.87 (3H, bs,
H-17)*, 1.86 (2H, m, H-2), 1.46 (2H, m, H-12), 1.19 (6H, s, H-15, H-16),
1.14 (3H, d, J¼6.1 Hz, H-14), 0.88 (9H, s, (CH3)3CSi), 0.05 (6H, s,
4.5.7. TBS-derivative of 4-dihydrotrisporin B (21). Starting from 18
(0.13 mL, 0.94 mmol), ruthenium catalyst 25 (26 mg, 0.031 mmol),
13 (200 mg, 0.62 mmol), CH2Cl2 (1.6 mL) and following the general
procedure (chromatography eluent hexane:Et2O 98:2), 21 was
obtained as an oil (170 mg, 0.44 mmol, 70% yield as a mixture E/Z
(CH3)2Si); 13C NMR (CDCl3, 75 MHz)
d (ppm) 199.42 (C, C-4), 161.77
(C, C-6), 133.25 (CH, C-8, C-10), 131.54 (C, C-9), 129.66 (C, C-5),
124.72 (CH, C-7), 68.08 (CH, C-13), 39.91 (CH2, C-12), 37.28 (CH2, C-
2), 35.59 (C, C-1), 34.26 (CH2, C-3), 27.52 (CH3, C-15, C-16), 25.82
(CH3, (CH3)3CSi), 23.90 (CH2, C-11), 23.71 (CH3, C-14), 20.07 (CH3, C-
17)*, 18.06 (C, (CH3)3CSi), 13.75 (CH3, C-18)*, ꢂ4.39 (CH3, (CH3)2Si),
ꢂ4.79 (CH3, (CH3)2Si). * may be interchanged.
2.5:1). IR
n
(cmꢂ1) 2930, 2856, 1720, 1675, 1466, 1359, 1254, 1081,
1047, 835, 773. HRFABMS (m/z): calcd (C24H42O2SiNa): 413.2852,
found: 413.2821 [MþNa]þ; A small amount of this mixture was
rechromatographied and both isomers were isolated.
4.5.7.1. (Z). 1H NMR (CDCl3, 300 MHz)
d
(ppm) 6.42 (1H, d,
4.5.9.2. (E). 1H NMR (CDCl3, 300 MHz)
d (ppm) 6.23 (1H, d,
J¼16.6 Hz, H-8), 6.10 (1H, d, J¼16.6 Hz, H-7), 5.31 (1H, t, J¼6.9 Hz,
H-10), 4.05 (1H, t, J¼6.9 Hz, H-4), 2.48 (4H, m, H-11, H-12), 2.16 (3H,
s, H-14), 1.85 (3H, s, H-18), 1.75 (3H, s, H-17); 1.42 (2H, m, H-2), 1.24
J¼16.2 Hz, H-8), 6.08 (1H, d, J¼16.3 Hz, H-7), 5.60 (1H, t, J¼7.6 Hz,
H-10), 3.83 (1H, sext, J¼6.1 Hz, H-13), 2.51 (2H, t, J¼7.1 Hz, H-3),
2.28 (1H, m, H-10a), 2.19 (1H, m, H-10b), 1.87 (2H, m, H-2), 1.85 (3H,

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C. Lo´pez-Sanchez et al. / Tetrahedron 65 (2009) 9542–9549
9548
bs, H-18)*, 1.83 (3H, bs, H-17)*, 1.46 (2H, m, H-12), 1.18 (6H, s, H-15,
H-16), 1.16 (3H, d, J¼6.1 Hz, H-14), 0.90 (18H, s, (CH3)3CSi), 0.06
(12H, s, (CH3)2Si). * may be interchanged.
H-17)*, 1.83 (3H, s, H-18)*, 1.03 (3H, s, H-15), 1.00 (3H, s, H-16);
(common signals) (ppm) 3.98 (1H, m, H-4), 2.16 (2H, m, H-11), 1.68
(4H, m, H-3, H-2), 1.35 (4H, m, H-12, H-13), 0.90 (3H, t, J¼6.1 Hz, H-
14); 13C NMR (CDCl3, 75 MHz) (signals due to the E isomer)
(ppm)
d
d
4.5.10. TBS-derivative of 4-desoxytrisporin C (24). Starting from 19
(256 mg, 1.06 mmol), ruthenium catalyst 25 (22 mg, 0.026 mmol),
16 (100 mg, 0.53 mmol), CH2Cl2 (1.5 mL) and following the general
procedure (chromatography eluent hexane:Et2O 98:2), 24 was
obtained as an oil (150 mg, 0.40 mmol, 75% yield as a mixture E/Z
141.84 (C, C-6), 138.91 (CH, C-8), 133.49 (C, C-9), 132.46 (CH, C-10),
128.98 (C, C-5), 123.03 (CH, C-7), 34.64 (C, C-1), 31.77 (CH2, C-12),
27.97 (CH2, C-11), 22.40 (CH2, C-13), 18.57 (CH3, C-17), 12.14 (CH3,
C-18); (signals due to the Z isomer)
d (ppm) 142.10 (C, C-6), 133.09
(C, C-9), 130.71 (CH, C-8), 129.39 (C, C-5), 127.92 (CH, C-10), 126.85
(CH, C-7), 34.58 (C, C-1), 32.18 (CH2, C-12), 27.01 (CH2, C-11), 22.24
(CH2, C-13), 20.32 (CH3, C-17)*, 18.57 (CH3, C-18)*; (common sig-
1.8:1). IR
n
(cmꢂ1) 2957, 2928, 2857, 1461, 1360, 1256, 1134, 1089,
1031, 966, 835, 773. HRFABMS (m/z): calcd (C24H44OSiNa):
399.3059, found: 399.3036 [MþNa]þ; 1H NMR (CDCl3, 300 MHz)
nals)
d (ppm) 70.10 (CH, C-4), 34.48 (CH2, C-2), 28.96 (CH3, C-15),
(signals due to the E isomer)
d
(ppm) 6.02 (2H, bs, H-7, H-8), 5.45 (1H,
28.43 (CH2, C-3), 27.38 (CH3, C-16), 13.94 (CH3, C-14).* may be
interchanged.
t, J¼7.3 Hz, H-10), 1.82 (3H, s, H-17)*, 1.73 (3H, s, H-18)*; (signals due
to the Z isomer)
(ppm) 6.45 (1H, d, J¼16.1 Hz, H-8), 6.11 (1H, d,
J¼16.1 Hz, H-7), 5.38 (1H, d, J¼8.1 Hz, H-10), 1.85 (3H, s, H-17)*, 1.74
(3H, s, H-18)*; (common signals) (ppm) 3.84 (1H, m, H-13), 2.25
d
4.6.4. 4-Dihydrotrisporin B (4). Following the general procedure,
21 (100 mg, 0.26 mmol), n-Bu4NF (1 M in THF, 0.78 mL, 0.78 mmol)
and THF (1.3 mL) yielded 4 as an oil (50 mg, 0.18 mmol, 70%). IR and
HRMS signals as previously reported.28 1H NMR (CDCl3, 300 MHz)
d
(2H, m), 2.04 (2H, m), 1.55–1.45 (6H, m), 1.19 (3H, d, J¼5.9 Hz, H-14),
1.05 (6H, s, H-15, H-16), 0.93 (9H, s, (CH3)3CSi), 0.09 (6H, s,
(CH3)2Si); 13C NMR (CDCl3, 75 MHz)
d
(ppm) (signals due to the E
(signals due to the E isomer) d (ppm) 6.09–5.98 (2H, m, H-7, H-8),
isomer) 137.96 (CH, C-8), 137.85 (C, C-6), 132.40 (C, C-9), 130.99 (CH,
C-10), 128.06 (C, C-5), 124.02 (CH, C-7), 39.83 (CH2, C-12), 24.63
(CH2, C-11), 21.66 (CH3, C-17)*, 12.14 (CH3, C-18)*; (signals due to the
Z isomer) 138.13 (C, C-6),131.15 (C, C-9),130.28 (CH, C-8), 129.12 (CH,
C-10), 128.50 (C, C-5), 126.85 (CH, C-7), 40.14 (CH2, C-12), 24.38
(CH2, C-11), 20.35 (CH3, C-17)#,17.55 (CH3, C-18)#; (common signals)
5.37 (1H, t, J¼7.3 Hz, H-10), 2.16 (3H, s, H-14), 1.80 (6H, s, H-17, H-
18),1.02 (3H, s, H-15), 0.99 (3H, s, H-16); (signals due to the Z isomer)
d
(ppm) 6.42 (1H, d, J¼16.2 Hz, H-8), 6.09–5.98 (1H, m, H-7), 5.31
(1H, t, J¼7.2 Hz, H-10), 2.14 (3H, s, H-14), 1.85 (3H, s, H-17)*, 1.83
(3H, s, H-18)*,1.03 (3H, s, H-15),1.00 (3H, s, H-16); (common signals)
d
(ppm) 4.00 (1H, bs, H-4), 2.54–2.41 (4H, m, H-11, H-12), 1.67 (4H,
m, H-2, H-3); 13C NMR (CDCl3, 75 MHz) (signals due to the E isomer)
(ppm) 141.84 (C, C-6), 138.40 (CH, C-8),134.70 (C, C-9),129.82 (CH,
d
(ppm) 68.28 (CH, C-13), 39.53 (CH2, C-2), 34.07 (C, C-1), 32.89
(CH2, C-4), 28.85 (CH3, C-15, C-16), 25.86 (CH3, (CH3)3CSi), 23.72
(CH3, C-14), 19.30 (CH2, C-3), 18.07 (C, (CH3)3CSi), ꢂ4.43 (CH3,
(CH3)2Si), ꢂ4.80 (CH3, (CH3)2Si).*,# may be interchanged.
d
C-10), 129.11 (C, C-5), 123.95 (CH, C-7), 70.11 (CH, C-4), 43.30 (CH2,
C-12), 34.62 (C, C-1), 29.87 (CH3, C-14), 22.55 (CH2, C-11), 18.51
(CH3, C-17), 12.17 (CH3, C-18); (signals due to the Z isomer)
d (ppm)
4.6. TBS deprotection
142.10 (C, C-6), 133.09 (C, C-9), 130.71 (CH, C-8), 129.39 (C, C-5),
127.92 (CH, C-10), 126.85 (CH, C-7), 70.16 (CH, C-4), 43.80 (CH2, C-
12), 34.67 (C, C-1), 29.89 (CH3, C-14), 21.69 (CH2, C-11), 20.28 (CH3,
4.6.1. General TBS-deprotection procedure. To a solution of the
silylether in THF (5 mL/mmol), n-Bu4NF (1 M in THF, 3 equiv) was
added. The reaction mixture was stirred under reflux for 12 h. Then,
the solvent was removed under reduced pressure and the residue
was dissolved in Et2O, washed with brine, dried over MgSO4 and
the solvent was removed again under reduced pressure. Purifica-
tion was achieved on silica using hexane:Et2O (1:1) for elution.
C-17)*, 18.56 (CH3, C-18)*; (common signals)
d (ppm) 208.32 (C, C-
13), 37.43 (CH2, C-2), 28.43 (CH2, C-3), 28.97 (CH3, C-15), 27.35 (CH3,
C-s16). *,# may be interchanged.
4.6.5. 4-Dihydrotrisporin C (7). Following the general procedure,
but at room temperature, 22 (97 mg, 0.19 mmol), n-Bu4NF (1 M in
THF, 1.1 mL, 1.1 mmol) and THF (1 mL) yielded 7 as an oil (28 mg,
4.6.2. Compound 14. Following the general procedure, 13 (1 g,
3.13 mmol), n-Bu4NF (1 M in THF, 9.4 mL, 9.4 mmol) and THF
(16 mL) yielded (E)-2,4,4-trimethyl-3-(3-methylbuta-1,3-dienyl)-
0.10 mmol, 55%). IR and HRMS signals as previously reported.28
A
small amount of this mixture was rechromatographied and both
isomers were isolated.
2-cyclohexenol (14) (630 mg, 3.07 mmol, 95%). Oil, IR
n )
(cmꢂ1
3335, 2960, 2935, 2862, 1602, 1602, 1449, 966; HRFABMS (m/z):
4.6.5.1. (Z).
d
(ppm) 6.46 (1H, dd, J¼16.2 Hz, J¼4.0 Hz, H-8), 6.12
calcd (C14H22ONa): 229.1568, found: 229.1595 [MþNa]þ; 1H NMR
(1H, bd, J¼16.2 Hz, H-7), 5.49 (1H, m, H-10), 4.02 (1H, m, H-4), 3.81
(1H, m, H-13), 1.85 (3H, s, H-17)*, 1.84 (3H, s, H-18)*, 1.20 (3H, d,
J¼6.4 Hz, H-14), 1.05 (3H, s, H-15), 1.02 (3H, s, H-16). * may be
interchanged.
(300 MHz, CDCl3)
d
(ppm) 6.12 (1H, d, J¼16.2 Hz, H-8), 6.03 (1H, d,
J¼16.5 Hz, H-7), 4.95 (1H, bs, H-10a), 4.93 (1H, bs, H-10b), 3.98 (1H,
t, J¼4.4 Hz, H-4), 1.89 (3H, s, H-13)*, 1.85 (1H, m), 1.81 (3H, s, H-14),
1.63 (2H, m), 1.41 (1H, m), 1.02 (3H, s, H-11), 0.99 (3H, s, H-12); 13C
NMR (75 MHz, CDCl3)
d
(ppm) 142.00 (C, C-9), 141.33 (C, C-6),
4.6.5.2. (E). 1H NMR (CDCl3, 300 MHz) (E isomer)
d (ppm) 6.03
136.66 (CH, C-8), 129.65 (C, C-5), 126.59 (CH, C-7), 115.75 (CH2, C-
10), 69.97 (CH, C-4), 34.61 (C, C-1), 34.47 (CH2, C-2), 28.90 (CH3, C-
11), 28.41 (CH2, C-3), 27.38 (CH3, C-12), 18.47 (CH3, C-13)*, 18.38
(CH3, C-14)*. * may be interchanged.
(2H, m, H-7, H-8), 5.46 (1H, t, J¼6.9 Hz, H-10), 4.01 (1H, m, H-4),
3.86 (1H, m, H-13), 2.30 (2H, m), 2.20 (2H, m),1.86 (2H, m),1.83 (6H,
s, H-17, H-18), 1.45 (2H, m), 1.23 (3H, d, J¼6.1 Hz, H-14), 1.05 (3H, s,
H-15), 1.01 (3H, s, H-16).
4.6.3. 4-Dihydrotrisporin A (1). Following the general procedure,
20 (88 mg, 0.23 mmol), n-Bu4NF (1 M in THF, 0.7 mL, 0.7 mmol)
and THF (1.2 mL) yielded 1 as an oil (30 mg, 0.11 mmol, 50%). IR and
HRMS signals as previously reported.28 1H NMR (CDCl3, 300 MHz)
4.6.6. Trisporin C (8). Following the general procedure, 23 (115 mg,
0.29 mmol), n-Bu4NF (1 M in THF, 0.9 mL, 0.9 mmol) and THF
(1.5 mL) yielded 8 as an oil (24 mg, 0.09 mmol, 30%). IR and HRMS
signals as previously reported.28 1H NMR (CDCl3, 300 MHz) (signals
(signals due to the E isomer)
d
(ppm) 6.03 (1H, d, J¼16.2 Hz, H-8),
due to the E isomer)
J¼16.3 Hz, H-7), 5.59 (1H, t, J¼6.7 Hz, H-10); (signals due to the Z
isomer)
(ppm) 6.66 (1H, d, J¼16.0 Hz, H-8), 6.22 (1H, d, J¼16.0 Hz,
H-7), 5.57 (1H, m, H-10); (common signals) (ppm) 3.84 (1H, m, H-
13), 2.50 (2H, m, H-3), 2.29 (2H, m, H-11), 1.84 (6H, s, H-17, H-18),
d
(ppm) 6.22 (1H, d, J¼16.4 Hz, H-8), 6.09 (1H, d,
5.90 (1H, d, J¼16.2 Hz, H-7), 5.42 (1H, t, J¼7.3 Hz, H-10), 1.81 (3H, s,
H-17), 1.77 (3H, s, H-18), 1.02 (3H, s, H-15), 0.99 (3H, s, H-16);
d
(signals due to the Z isomer)
6.03 (1H, d, J¼16.2 Hz, H-7), 5.37 (1H, t, J¼7.2 Hz, H-10), 1.84 (3H, s,
d
(ppm) 6.44 (1H, d, J¼16.2 Hz, H-8),
d

´
C. Lo´pez-Sanchez et al. / Tetrahedron 65 (2009) 9542–9549
9549
1.74 (2H, m, H-2), 1.55 (2H, m, H-12), 1.23 (3H, d, J¼6.2 Hz, H-14),
1.18 (3H, s, H-15), 1.16 (3H, s, H-16); 13C NMR (CDCl3, 75 MHz)
(ppm) (signals due to the E isomer) 198.74 (C, C-4), 163.40 (C, C-6),
References and notes
1. Plempel, M. Planta 1963, 59, 492–508.
2. Austin, D. J.; Bu’Lock, J. D.; Gooday, G. W. Nature 1969, 223, 1178–1179.
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4. Miller, M. L.; Sutter, R. P. J. Biol. Chem. 1984, 259, 6420–6422.
5. Werkman, B. A. Arch. Microbiol. 1976, 109, 209–213.
6. Gooday, G. W. Phytochemistry 1968, 7, 2103–2105.
7. Bu’Lock, J. D.; Jones, B. E.; Winskill, N. Pure Appl. Chem. 1976, 47, 191–202.
8. Nieuwenhuis, M.; van den Ende, H. Arch. Microbiol. 1975, 102, 167–169.
9. Sutter, R. P.; Whitaker, J. P. Naturwissenschaften 1981, 68, 147–148.
10. Gessler, N. N.; Sokolov, A. V.; Belozerskaya, T. A. Appl. Biochem. Microbiol. 2002,
38, 536–543.
d
141.06 (CH, C-8), 134.78 (CH, C-10), 133.77 (C, C-9), 129.49 (C, C-5),
122.33 (CH, C-7), 23.58 (CH3, C-17)*, 13.70 (CH3, C-18)*; (signals due
to the Z isomer) 199.52 (C, C-4), 161.79 (C, C-6), 133.09 (CH, C-8),
132.63 (CH, C-10), 131.98 (C, C-9), 129.68 (C, C-5), 125.05 (CH, C-7),
20.12 (CH3, C-17)#, 12.08 (CH3, C-18)#; (common signals)
d (ppm)
67.64 (CH, C-13), 38.68 (CH2, C-12), 37.25 (CH2, C-2), 35.59 (C, C-1),
34.24 (CH2, C-3), 27.52 (CH3, C-15, C-16), 26.65 (CH3, C-14), 23.99
(CH2, C-11).*,# may be interchanged.
11. Schachtschabel, D.; David, A.; Menzel, K. D.; Schimek, C.; Woestemeyer, J.;
Boland, W. ChemBioChem 2008, 9, 3004–3012.
12. Reschke, T. Tetrahedron Lett. 1969, 10, 3435–3439.
4.6.7. 4-Desoxytrisporin C (9). Following the general procedure, 24
(226 mg, 0.60 mmol), n-Bu4NF (1 M in THF, 1.8 mL, 1.8 mmol) and
THF (3 mL) yielded 9 (112 mg, 0.43 mmol, 71%). Oil, IR
13. Bu’Lock, J. D.; Drake, D.; Winstanley, D. J. Phytochemistry 1972, 11, 2011–2018.
14. Edwards, J. A.; Schwarz, V.; Fajkos, J.; Maddox, M. L.; Fried, J. H. J. Chem. Soc.,
Chem. Commun. 1971, 292–293.
n )
(cmꢂ1
15. Trost, B. M.; Ornstein, P. L. Tetrahedron Lett. 1983, 24, 2833–2836.
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17. Secrist, J. A., III; Hickey, C. J.; Norris, R. E. J. Org. Chem. 1977, 42, 525–527.
18. Prisbylla, M. P.; Takabe, K.; White, J. D. J. Am. Chem. Soc. 1979, 101, 762–763.
19. Takabe, K.; White, J. D. Tetrahedron Lett. 1983, 24, 3709–3712.
20. White, J. D.; Takabe, K.; Prisbylla, M. P. J. Org. Chem. 1985, 50, 5233–5244.
21. Bacigaluppo, J. A.; Colombo, M. I.; Cravero, R. M.; Gonzalez-Sierra, M.; Preite,
M. D.; Zinczuk, J.; Ruveda, E. A. Tetrahedron: Asymmetry 1994, 5, 1877–1880.
22. Bacigaluppo, J. A.; Colombo, M. I.; Preite, M. D.; Zinczuk, J.; Ruveda, E. A.; Seiler,
J. Tetrahedron: Asymmetry 1996, 7, 1041–1057.
3350, 2963, 2926, 2864, 1455, 1359, 966; HRFABMS (m/z): calcd
(C18H30ONa): 285.2194, found: 285.2215 [MþNa]þ; 1H NMR (CDCl3,
300 MHz) (signals due to the E isomer) d (ppm) 5.99 (2H, bs, H-7, H-
8), 5.41 (1H, t, J¼7.0 Hz, H-10),1.86 (3H, s, H-17)*,1.70 (3H, s, H-18)*;
(signals due to the Z isomer)
(ppm) 6.42 (1H, d, J¼16.2 Hz, H-8),
6.10 (1H, d, J¼16.2 Hz, H-7), 5.32 (1H, d, J¼7.0 Hz, H-10), 1.80 (3H, s,
H-17)#, 1.68 (3H, s, H-18)#; (common signals)
(ppm) 3.80 (1H, m,
d
d
H-13), 2.24 (2H, m), 1.99 (2H, m), 1.68–1.45 (6H, m), 1.20 (3H, d,
23. Colombo, M. I.; Zinczuk, J.; Mischne, M. P.; Ruveda, E. A. Pure Appl. Chem. 2001,
73, 623–626.
J¼5.9 Hz, H-14), 1.01 (6H, s, H-15, H-16); 13C NMR (CDCl3, 75 MHz)
24. Takahashi, S.; Oritani, T.; Yamashita, K. Agric. Biol. Chem. 1987, 51, 2291–2293.
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d
(ppm) (signals due to the E isomer) 137.72 (C, C-6), 137.70 (CH, C-8),
134.38 (C, C-9), 130.39 (CH, C-10), 128.23 (C, C-5), 124.36 (CH, C-7),
24.64 (CH2, C-11), 21.66 (CH3, C-17)*,12.24 (CH3, C-18)*; (signals due
to the Z isomer) 138.06 (C, C-6), 132.80 (C, C-9),129.99 (CH, C-8),
128.62 (CH, C-10), 128.41 (C, C-5), 127.28 (CH, C-7), 23.74 (CH2, C-
11), 21.60 (CH3, C-17)#, 20.43 (CH3, C-18)#; (common signals)
d
(ppm) 67.66 (CH, C-13), 39.98 (CH2, C-12), 39.48 (CH2, C-2), 34.11
(C, C-1), 32.83 (CH2, C-4), 28.84 (CH3, C-15, C-16), 23.42 (CH3, C-14),
19.25 (CH2, C-3). *,# may be interchanged.
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Synthesis 2006, 2760–2766.
Acknowledgements
´
We wish to acknowledge the Spanish Ministerio de Educacion y
Ciencia for financial support (Project CTQ2006-15575-C02-01/BQU)
and to Prof. A.F. Barrero and E. Cerda, coordinators of the other parts
of the multidisciplinary project.
´