Stereoselective synthesis of the published structure of feigrisolide A. Structural revision of feigrisolides A and B

Article abstract of DOI:10.1021/jo060314q

The total synthesis of the proposed structure of feigrisolide A is reported. Ethyl (S)-3-hydroxybutyrate was the chiral starting material. A Brown asymmetric allylation and an Evans aldol reaction were key steps of the synthesis. The NMR data of the synth

Full text of DOI:10.1021/jo060314q

Stereoselective Synthesis of the Published
Structure of Feigrisolide A. Structural Revision
of Feigrisolides A and B
Paula AÄ lvarez-Bercedo,† Juan Murga,† Miguel Carda,*,† and
J. Alberto Marco*,‡
Departamento de Qu´ımica Inorga´nica y Orga´nica, UniVersidad
Jaume I, E-12071 Castello´n, Spain and Departamento de
Qu´ımica Orga´nica, UniVersidad de Valencia,
E-46100 Burjassot, Valencia, Spain
alberto.marco@uV.es
ReceiVed February 15, 2006
FIGURE 1. Reported structures of feigrisolides A (1), B (2), C (3),
and D (4) and corrected structure of feigrisolide C (5).
were not determined. For their part, macrodiolide structures 3
and 4 were attributed, respectively, to feigrisolides C and D
upon comparison of their spectral data with those of 1 and 2,
which were assumed to be their biogenetic precursors.
Very recently, the compound with structure 2 and its triple
epimer at the carbon atoms C-2/C-3/C-6 have been prepared.3
Both products were found to differ from natural feigrisolide B.
Hereafter, Lee and co-workers succeeded in synthesizing 3 and
its C-3′ epimer, but their physical and spectroscopic features
did not match those of natural feigrisolide C. Finally, the latter
group was able to establish by means of synthesis that the actual
structure of feigrisolide C is 5.4
As shown in Figure 1, the proposed and actual structures of
feigrisolide C differ not only in stereochemical features but also
in their constitution: in contrast to 3, structure 5 contains two
tetrahydrofurane rings and no lactone moiety. It has been
assumed that compounds 1 and 2 are biosynthetic precursors
of 5. Fragments C1-C8 (left half) and C1′-C10′ (right half) of
feigrisolide C 5 would then be related to feigrisolide A 1 and
feigrisolide B 2, respectively. In this case, the configurations
at C-2 and C-8 in 1 should be R and S, respectively, as in 5.
Nothing can be predicted, however, in relation to C-3 and C-6,
as both stereocenters are part of a tetrahydrofuran ring in 5 but
not in 1. On the basis of NOE studies, Thiericke and co-workers1
deduced a spatial proximity between H-3 and H-6, which are
thus in a syn arrangement. However, these authors did not
comment on the existence of NOE correlations between H-3
(or H-6) and H-2. Thus, the relative configuration proposed for
C-2 and C-3 relied upon molecular mechanics studies. Obvi-
ously, stereochemical ambiguities still persist. For this reason,
we have decided to undertake the total synthesis of feigrisolide
A to confirm or disregard structure 1.
The total synthesis of the proposed structure of feigrisolide
A is reported. Ethyl (S)-3-hydroxybutyrate was the chiral
starting material. A Brown asymmetric allylation and an
Evans aldol reaction were key steps of the synthesis. The
NMR data of the synthetic product are different from those
of the natural product. The published structure of feigrisolide
A is therefore erroneous. A subsequent comparison of
spectral data strongly suggests that feigrisolides A and B
are identical with (-)-nonactic acid and (+)-homononactic
acid, respectively.
Introduction
Feigrisolides A-D constitute a group of lactones isolated
from the culture broth of strain GT 051022 of Streptomyces
griseus. They were found to display various degrees of activities
in antibacterial, antiviral, cytotoxic, and enzyme inhibition
assays.1 Their structures were assigned to be 1-4 (Figure 1),
mainly on the basis of spectroscopic analyses. In the case of
seven-membered lactones 1 and 2 (feigrisolides A and B), the
relative configurations of the three ring stereocenters were
established through NOE measurements, supported by molecular
mechanics calculations. The absolute configuration at C-8 was
established as S for 1 and R for 2 with the aid of Helmchen’s
method,2 but the absolute configurations of the whole molecules
Our retrosynthetic concept for the preparation of 1 is shown
in Scheme 1. The seven-membered lactone ring is to be created
* (M.C.) Address: Departamento de Qu´ımica Inorga´nica y Orga´nica, Uni-
versidad Jaume I, Avda. Sos Baynat s/n, E-12071 Castello´n, Spain. Phone: 34-
964-728174. (J.A.M.) Address: Departamento de Qu´ımica Orga´nica, Universidad
de Valencia, c/D. Moliner, 50, E-46100 Burjassot, Spain. Phone: 34-96-3544337.
Fax: 34-96-3544328.
(3) Sharma, G. V. M.; Kumar, K. R. Tetrahedron: Asymmetry 2004,
15, 2323-2326.
(4) (a) Kim, W. H.; Jung, J. H.; Sung, L. T.; Lim, S. M.; Lee, E. Org.
Lett. 2005, 7, 1085-1087. (b) Kim, W. H.; Jung, J. H.; Lee, E. J. Org.
Chem. 2005, 70, 8190-8192. See also the following: Lee, E.; Sung, L. T.;
Hong, S. K. Bull. Kor. Chem. Soc. 2002, 23, 1189-1190.
† University Jaume I.
‡ University de Valencia.
(1) Tang, Y.-Q.; Sattler, I.; Thiericke, R.; Grabley, S.; Feng, X.-Z. J.
Antibiot. 2000, 53, 934-943.
(2) Helmchen, G. Tetrahedron Lett. 1974, 16, 1527-1530.
10.1021/jo060314q CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/23/2006
5766
J. Org. Chem. 2006, 71, 5766-5769

SCHEME 1. Retrosynthetic Analysis of Structure 1
SCHEME 2. Stereoselective Synthesis of Lactone 1a
by lactonization of the protected trihydroxy acid I. The latter is
derived from a syn-selective aldol reaction of aldehyde II with
a suitable chiral propionate equivalent III. Aldehyde II in turn
should be prepared via IV from the commercially available ethyl
(S)-3-hydroxybutyrate 6 through reduction, asymmetric allyla-
tion, and suitable functional manipulation.
Results and Discussion
a Reagents and conditions: (a) ref 5; (b) allylBIpc2 [from (-)-Ipc2BCl
and allylmagnesium bromide], Et2O, -100 °C, 1 h, (89:11 mixture of
diastereoisomers), 70% of 8 after chromatographic separation; (c) benzyl
trichloroacetimidate, TfOH, CH2Cl2, room temp, 3 h, 83%; (d) 9-BBN, THF,
room temp, 18 h, 77%; (e) Swern; (f) 17, Bu2BOTf, Et3N, CH2Cl2, 0 °C,
then addition of the resulting boron enolate to the aldehyde, 0 °C, 18 h,
70% overall; (g) TBSOTf, 2,6-lutidine, CH2Cl2, room temp, 1 h, 85%; (h)
LiOH, H2O2, aq THF, room temp, 24 h, 76%; (i) Pd/C, H2, EtOAc, room
temp, 2 h, 84%; (j) 2,4,6-trichlorobenzoyl chloride, EtNiPr2, DMAP, 1 h,
THF, RT, 87%; (k) HF-pyridine, pyridine, THF, 24 h, 55 °C, 70%; (l) Ac2O,
pyridine, room temp, 12 h, 80%. Nonstandard abbreviations and acro-
nyms: Ipc, isopinocampheyl; TBS, tert-butyldimethylsilyl; TPS, tert-
butyldiphenylsilyl.
Scheme 2 depicts the details of the synthesis. The known
aldehyde 7 was prepared as reported5 by protection of the
commercially available ethyl (S)-3-hydroxybutyrate 6 as its TPS
ether followed by reduction with DIBAL. Reaction of 7 with
allylBIpc2, prepared as described from (-)-Ipc2BCl and allyl-
magnesium bromide,6 gave homoallyl alcohol 8 as a chromato-
graphically separable 89:11 diastereoisomeric mixture. Benzyl-
ation of the hydroxyl group was performed with benzyl
trichloroacetimidate7 and yielded 9, which was then subjected
to hydroboration-oxidation to yield primary alcohol 10. The
remaining stereocenters were generated with the aid of the Evans
asymmetric aldol methodology.8 Alcohol 10 was oxidized to
the corresponding aldehyde, and the latter was allowed to react
with the boron Z-enolate of N-propionyl oxazolidinone 17. This
gave aldol adduct 11 as a single stereoisomer. Silylation to 12
and hydrolytic cleavage of the chiral auxiliary furnished the
protected trihydroxy acid 13. Selective cleavage of the O-benzyl
group provided 14, which was subjected to the Yamaguchi
lactonization protocol9 to afford 15.10 Cleavage of the two silyl
groups in 15 proved somewhat difficult11 but was finally
achieved by treatment with HF-pyridine in hot THF. This
completed the synthesis of dihydroxy lactone 1.
Unexpectedly, the physical and spectral properties of synthetic
1 turned out to be different from those reported for feigrisolide
A (see Supporting Information). As commented above, synthetic
work has shown that the published structures of feigrisolides
B3 and C4 are also erroneous.12 In fact, some additional features
also made structure 1 to appear suspicious. For instance,
acetylation of synthetic 1 under standard conditions (Ac2O,
pyridine, room temperature) provided diacetate 16, as expected.
In contrast, Thiericke et al. reported the formation of a
monoacetate from natural feigrisolide A under the same condi-
tions.1 Furthermore, the structure of feigrisolide C (5) contains
only tetrahydrofuran hydroxy acid fragments. We thus wondered
whether the alleged feigrisolide A might be identical with the
known compound (-)-nonactic acid 18 (Figure 2),13 which
contains the tetrahydrofuran moiety corresponding to the left
half of 5. Indeed, structures 1 and 18 have the same molecular
(5) Claffey, M. M.; Heathcock, C. H. J. Org. Chem. 1996, 61, 7646-
7647.
(6) Ramachandran, P. V.; Chen, G.-M.; Brown, H. C. Tetrahedron Lett.
1997, 38, 2417-2420. For a recent review on asymmetric allylborations,
see the following: Ramachandran, P. V. Aldrichimica Acta 2002, 35, 23-
35.
(7) Wessel, H.-P.; Iversen, T.; Bundle, D. R. J. Chem. Soc., Perkin Trans.
1 1985, 2247-2250.
(8) (a) Evans, D. A. Aldrichimica Acta 1982, 15, 23-32. (b) Kim, B.
M.; Williams, S. F.; Masamune, S. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Winterfeldt, E., Eds.; Pergamon Press: Oxford,
U.K., 1993; Vol. 2, pp 239-276. See also the following: Cowden, C. J.;
Paterson, I. Org. React. 1997, 51, 1-200.
(11) The TBS group proved reluctant to cleavage.
(12) According to the previous results and those presented here, it seems
likely that the structure of feigrisolide D will also need correction.
(13) (a) Gerlach, H.; Prelog, V. Justus Liebigs Ann. Chem. 1963, 669,
121-135. (b) Gerlach, H.; Wetter, H.-J. HelV. Chim. Acta 1974. 57, 2306-
2321.
(9) Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M. Bull.
Chem. Soc. Jpn. 1979, 52, 1989-1993.
(10) The structure of lactone 15 was confirmed by means of an X-ray
diffraction study (see Supporting Information).
J. Org. Chem, Vol. 71, No. 15, 2006 5767

from above in dry CH2Cl2 (10 mL). The mixture was then stirred
for another 18 h and quenched through the addition of phosphate
pH 7 buffer solution (15 mL), MeOH (15 mL), and 30% H2O2
(7.5 mL). After stirring for 30 min at room temp, the mixture was
poured onto saturated aq NaHCO3 and worked up (extraction with
CH2Cl2). Column chromatography of the oily residue on silica gel
(hexanes-EtOAc, 4:1) yielded 11 (1.19 g, 70% overall from 10):
amorphous solid; [R]D +3.4 (c 2, CHCl3).1H NMR (500 MHz,
CDCl3): δ 7.75-7.70 (4H, m), 7.50-7.20 (16H, br m), 5.64 (1H,
d, J ) 6.9 Hz), 4.77 (1H, quint, J ) 6.9 Hz), 4.45 (1H, d, J ) 11.3
Hz), 4.27 (1H, d, J ) 11.3 Hz), 4.14 (1H, m), 3.92 (1H, m), 3.79
(1H, m), 3.68 (1H, m), 1.75-1.70 (3H, m), 1.60-1.50 (4H, m),
1.25 (3H, d, J ) 6.9 Hz), 1.10 (3H, d, J ) 6.3 Hz), 1.09 (9H, s),
0.90 (3H, d, J ) 6.3 Hz). 13C NMR (125 MHz): δ 177.1, 152.6,
138.8, 134.8, 134.3, 133.2, 19.3 (C), 135.9, 135.8, 129.5, 129.4,
128.7, 128.6, 128.2, 127.6, 127.5, 127.4, 125.6, 78.9, 76.1, 71.7,
67.3, 54.8, 42.5 (CH), 70.7, 44.9, 30.1, 29.2 (CH2), 27.1 (x 3),
24.4, 14.3, 10.6 (CH3). IR νmax: 3500 (br, OH), 1782, 1698 (CdO)
cm-1. HR FAB MS m/z: 708.3755 (M + H+). Calcd for C43H54-
NO6Si, 708.3720.
Oxazolidinone 12. Oxazolidinone 11 (1.06 g, 1.5 mmol) was
dissolved in dry CH2Cl2 (20 mL) and treated sequentially with 2,6-
lutidine (875 µL, 7.5 mmol) and TBSOTf (1.38 mL, 6 mmol). The
reaction mixture was then stirred for 1 h at room temp and worked
up (extraction with CH2Cl2). Column chromatography on silica gel
(hexanes-EtOAc, 19:1) afforded the desired 12 (1.05 g, 85%): oil;
[R]D +6.8 (c 1.5, CHCl3). 1H NMR (500 MHz, CDCl3): δ 7.75-
7.70 (4H, m), 7.50-7.20 (16H, br m), 5.49 (1H, d, J ) 7 Hz),
4.62 (1H, quint, J ) 7 Hz), 4.44 (1H, d, J ) 11 Hz), 4.24 (1H, d,
J ) 11 Hz), 4.14 (1H, m), 4.06 (1H, m), 3.89 (1H, m), 3.65 (1H,
m), 1.75-1.60 (6H, m), 1.21 (3H, d, J ) 6.8 Hz), 1.10 (3H, d, J
) 6.3 Hz), 1.09 (9H, s), 0.94 (9H, s), 0.90 (3H, d, J ) 6.5 Hz),
0.09 (3H, s), 0.08 (3H, s). 13C NMR (125 MHz): δ 175.1, 152.6,
138.9, 134.8, 134.3, 133.2, 19.2, 18.0 (C), 135.9, 135.8, 129.5,
129.4, 128.6, 128.5, 128.2, 127.6, 127.5, 127.4, 125.6, 78.7, 76.5,
73.3, 67.3, 55.2, 42.8 (CH), 70.7, 45.2, 30.9, 29.2 (CH2), 27.1 (x
3), 25.9 (x 3), 24.4, 14.1, 12.2, -4.1, -4.8 (CH3). IR νmax: 1783,
1705 (CdO) cm-1. HR EIMS m/z (% relative intensity): 764.3784
(M+-tBu, 1), 656 (2), 199 (56), 91 (100). Calcd for C49H67NO6-
Si2-tBu, 764.3802.
(2R,3S,6S,8S)-6-Benzyloxy-3-(tert-butyldimethylsilyloxy)-8-
(tert-butyldiphenylsilyloxy)-2-methylnonanoic Acid (13). Com-
pound 12 (1.05 g, 1.27 mmol) from above was dissolved in a 2:1
THF/H2O mixture (20 mL) and treated with lithium hydroxide
monohydrate (105 mg, 2.5 mmol) and 30% aq H2O2 (0.8 mL). The
mixture was stirred at room temp for 24 h and poured onto 1.6 M
Na2SO3, followed by workup (extraction with CH2Cl2). Column
chromatography on silica gel (hexanes-EtOAc, 4:1) afforded acid
13 (644 mg, 76%): oil; [R]D -3 (c 2, CHCl3). 1H NMR (500 MHz,
CDCl3): δ 7.70-7.65 (4H, m), 7.50-7.20 (11H, br m), 4.40 (1H,
d, J ) 11.3 Hz), 4.24 (1H, d, J ) 11.3 Hz), 4.12 (1H, sext, J ) 6
Hz), 4.00 (1H, dt, J ) 4.5, 6 Hz), 3.60 (1H, quint, J ) 5.5 Hz),
2.59 (1H, dq, J ) 4.5, 7 Hz), 1.68 (2H, m), 1.60-1.50 (4H, m),
1.40 (1H, m), 1.14 (3H, d, J ) 7 Hz), 1.10 (3H, d, J ) 6 Hz), 1.07
(9H, s), 0.91 (9H, s), 0.09 (3H, s), 0.08 (3H, s). 13C NMR (125
MHz): δ 178.7, 138.8, 134.8, 134.3, 19.3, 18.0 (C), 135.9, 135.8,
129.6, 129.5, 128.3, 127.6, 127.5, 127.4, 76.3, 73.7, 67.3, 44.3 (CH),
70.8, 45.1, 29.9, 29.5 (CH2), 27.1 (x 3), 25.8 (x 3), 24.5, 10.9,
-4.3, -4.8 (CH3). IR νmax: 3500-2500 (br, COOH), 1708 (Cd
O) cm-1. HR EIMS m/z (% relative intensity): 605.3142 (M+-
tBu, 1), 497 (8), 199 (46), 91 (100). Calcd for C39H58O5Si2-tBu,
605.3118.
FIGURE 2. The structures of (-)-nonactic acid (18) and (+)-
homononactic acid (19).
weight and C/H atom connectivity. Furthermore, both would
show the NOE between H-3 and H-6 reported for feigrisolide
A.1 Structure 18 for feigrisolide A would also explain the
formation of a monoacetylated derivative, instead of the
expected diacetate. A direct comparison of feigrisolide A and
nonactic acid was not possible, because of the nonavailability
of authentic samples of the natural compounds. Moreover,
accurate, high-resolution 1H and 13C NMR data of free nonactic
acid have not been reported in the literature.14 Fortunately, these
data were sent to us by Prof. Eun Lee (see acknowledgments).4
After comparison with the NMR data of feigrisolide A (see the
Supporting Information), we have been able to conclude that
feigrisolide A is identical with 18. Structure 1 therefore does
not correspond to any natural product reported to date.
Following the same line of reasoning disclosed above,
feigrisolide B should correspond to the right half of the structure
of feigrisolide C and be thus identical with the known compound
(+)-homononactic acid 19 (Figure 2).15 High-resolution 1H and
13C NMR data of 19 were also sent to us by Prof. E. Lee.
Comparison with those of feigrisolide B (see Supporting
Information) leads to the conclusion that both compounds are
identical. This explains the failure of the previous attempt by
Sharma and Kumar3 at synthesizing feigrisolide B.
Conclusions
We have performed a stereoselective synthesis of the structure
published for the natural compound named feigrisolide A. It
has been found that the published structure does not correspond
to that of the natural product. A revised structure is proposed
not only for feigrisolide A but also for the closely related
feigrisolide B.
Experimental Section
General Features and Reaction Conditions. Described in the
Supporting Information.
Oxazolidinone 11. DMSO (0.42 mL, 6 mmol) was dissolved in
dry CH2Cl2 (6 mL), cooled to -78 °C and treated with oxalyl
chloride (265 µL, ca. 3 mmol). After stirring at this temp for 5
min, a solution of 10 (1.15 g, 2.4 mmol) in dry CH2Cl2 (2 mL)
was added dropwise, followed by triethylamine (1.7 mL, ca. 12
mmol). The reaction mixture was stirred for 15 min at -78 °C and
then for another 60 min at 0 °C. Workup (extraction with CH2Cl2)
and evaporation in vacuo provided a crude aldehyde which was
directly used in the next step.
A solution of oxazolidinone 14 (2.33 g, 10 mmol) in dry CH2-
Cl2 (20 mL) was cooled to 0 °C and treated sequentially with a 1
M solution of Bu2BOTf in CH2Cl2 (11 mL, 11 mmol) and
triethylamine (1.8 mL, ca. 13 mmol). The mixture was then stirred
for 1 h, followed by the addition of a solution of the crude aldehyde
(2R,3S,6S,8S)-3-(tert-Butyldimethylsilyloxy)-8-(tert-butyldiphen-
ylsilyloxy)-6-hydroxy-2-methylnonanoic Acid (14). An amount
of 10% Pd/C (300 mg) was suspended in EtOAc (5 mL) under an
H2 atmosphere. Acid 13 (630 mg, 0.95 mmol) dissolved in EtOAc
(15 mL) was then added via syringe. The mixture was stirred at
room temp and ambient pressure for 2 h and then filtered through
(14) We have only found 1H NMR data of (+)-nonactic acid: Fraser,
B.; Perlmutter, P. J. Chem. Soc., Perkin Trans. 1 2002, 2896-2899.
(15) (a) Schmidt, U.; Werner, J. Synthesis 1986, 986-992. (b) Kiyota,
H.; Abe, M.; Ono, Y.; Oritani, T. Synlett 1997, 1093-1095. See also the
following: Stadler, M.; Bauch, F.; Henkel, T.; Mu¨hlbauer, A.; Mu¨ller, H.;
Spaltmann, F.; Weber, K. Arch. Pharm. 2001, 334, 143-147.
5768 J. Org. Chem., Vol. 71, No. 15, 2006

Celite. Solvent removal in vacuo and column chromatography on
silica gel (hexanes-EtOAc, 4:1) gave hydroxy acid 14 (457 mg,
84%): oil; [R]D -11.5 (c 1.45, CHCl3). 1H NMR (500 MHz,
CDCl3): δ 7.70-7.65 (4H, m), 7.45-7.35 (6H, m), 4.18 (1H, sext,
J ) 6 Hz), 4.02 (1H, m), 3.98 (1H, m), 2.60 (1H, dq, J ) 4.5, 7
Hz), 1.70-1.30 (8H, br m), 1.15 (3H, d, J ) 7 Hz), 1.11 (3H, d,
J ) 6 Hz), 1.08 (9H, s), 0.90 (9H, s), 0.10 (3H, s), 0.09 (3H, s).
13C NMR (125 MHz): δ 178.7, 133.9, 133.3, 19.1, 18.0 (C), 135.9,
135.8, 129.9, 129.8, 127.7, 127.6, 73.5, 68.7, 68.1, 44.4 (CH), 44.3,
33.2, 29.9 (CH2), 27.1 (x 3), 25.8 (x 3), 22.6, 11.1, -4.3, -4.8
(CH3). IR νmax: 3500-2500 (br, COOH), 1709 (CdO) cm-1. HR
EIMS m/z (% relative intensity): 515.2635 (M+-tBu, 1), 497 (8),
305 (22), 199 (100), 75 (50). Calcd for C32H52O5Si2-tBu, 515.2649.
Lactone 15. The hydroxy acid 14 from above was dissolved in
dry THF (50 mL) and treated sequentially with ethyl diisopropyl-
amine (175 µL, 1 mmol), DMAP (6 mg, 0.05 mmol), and 2,4,6-
trichlorobenzoyl chloride (125 µL, 0.8 mmol). The mixture was
stirred at room temp for 1 h. Workup (extraction with Et2O) and
column chromatography on silica gel (hexanes-EtOAc, 9:1)
afforded lactone 15 (385 mg, 87%): solid; mp 77-78 °C; [R]D
in THF (6 mL) containing pyridine (0.6 mL) and treated with a
solution of pyridine (1 mL) and HF-pyridine complex (1.35 mL)
in THF (12 mL). The mixture was stirred for 24 h at 55 °C. Workup
(extraction with EtOAc) and column chromatography on silica gel
(EtOAc) afforded lactone 1 (92 mg, 70%): oil; [R]D +47.4 (c 1.2,
CHCl3) (literature values1 for feigrisolide A, [R]D +3.4 (c 0.3,
MeOH)). IR νmax: 3400 (br, OH), 1700 (CdO) cm-1. HR EIMS
m/z (% relative intensity): 203.1287 (M + H+, 5), 185 (6), 169
(20), 143 (30), 140 (100), 125 (50), 114 (58). Calcd for C10H19O4,
203.1283. Anal. Calcd for C10H18O4: C, 59.39; H, 8.97. Found:
C, 59.52; H, 9.02. For NMR data, see Table 1 in Supporting
Information.
Acknowledgment. Financial support has been granted by
the Spanish Ministry of Science and Technology (Projects
CTQ2005-06688-C02-01 and CTQ2005-06688-C02-02), by the
BANCAJA-UJI foundation (Project P1-1B2005-30), and by the
AVCyT (Project GV05/52). J. M. thanks the Spanish Ministry
of Education and Science for a contract of the Ramo´n y Cajal
program. P. A.-B. thanks the Spanish Ministry of Education
and Science for a predoctoral fellowship (FPI program). The
authors are also deeply indebted to Prof. Eun Lee, from the
Seoul National University, Korea, for the kind sending of high-
resolution NMR spectra of nonactic acid and homononactic acid.
1
+82 (c 0.65, CHCl3). H NMR (500 MHz, CDCl3): δ 7.70-7.65
(4H, m), 7.45-7.35 (6H, m), 4.63 (1H, td, J ) 10, 2.3 Hz), 4.22
(1H, m), 3.77 (1H, m), 3.10 (1H, dq, J ) 6.5, 7.5 Hz), 2.15-2.05
(1H, m), 1.90-1.75 (3H, m), 1.65 (1H, ddd, J ) 14.5, 9.5, 2.7
Hz), 1.58 (1H, dt, J ) 15, 4 Hz), 1.05 (3H, d, J ) 7.5 Hz), 1.04
(9H, s), 1.00 (3H, t, J ) 6.2 Hz), 0.87 (9H, s), 0.06 (3H, s), 0.03
(3H, s). 13C NMR (125 MHz, CDCl3): δ 174.4, 134.5, 19.3, 18.0
(C), 135.8, 135.7, 129.6, 127.6, 75.8, 70.1, 66.8, 50.5 (CH), 47.6,
30.4, 29.3 (CH2), 27.1 (x 3), 25.7 (x 3), 24.3, 12.6, -5.0, -5.1
(CH3). IR νmax: 1726 (CdO) cm-1. HR EIMS m/z (% relative
intensity): 497.2564 (M+-tBu, 100), 453 (20), 419 (44), 283 (34),
199 (60). Calcd for C32H50O4Si2-tBu, 497.2543. Anal. Calcd for
C32H50O4Si2: C, 69.26; H, 9.08. Found: C, 69.37; H, 9.00.
(3R,4S,7S)-4-Hydroxy-7-[(S)-2-hydroxypropyl)]-3-methylox-
epan-2-one (1). Lactone 15 (360 mg, 0.65 mmol) was dissolved
Supporting Information Available: Description of general
features and experimental procedures; physical and spectral data
1
of compounds 8-10 and 16; graphical H and 13C NMR spectra
of compounds 1, 8-10, 13, 15, nonactic acid, and homononactic
acid; three tables with compared NMR data of 1, nonactic acid,
and homononactic acid with feigrisolide A and feigrisolide B (PDF).
A CIF file with crystallographic data of lactone 15. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO060314Q
J. Org. Chem, Vol. 71, No. 15, 2006 5769