Tandem ring-closing/cross-metathesis approach for the synthesis of synargentolide B and its stereoisomers

Article abstract of DOI:10.1002/ejoc.201300434

The stereoselective syntheses of synargentolide B and its three stereoisomers have been accomplished from L-(+)- and D-(-)-diethyl tartrates, D-ribose, and D-mannitol as chiral pool starting materials. The key step was a tandem ring-closing/cross-metathes

Full text of DOI:10.1002/ejoc.201300434

FULL PAPER
DOI: 10.1002/ejoc.201300434
Tandem Ring-Closing/Cross-Metathesis Approach for the Synthesis of
Synargentolide B and Its Stereoisomers
Gowravaram Sabitha,*[a] Kontham Shankaraiah,[a] and Jhillu S. Yadav[a]
Keywords: Natural products / Tandem reactions / Metathesis / Cyclization / Structure elucidation
The stereoselective syntheses of synargentolide B and its
three stereoisomers have been accomplished from -(+)- and
-(–)-diethyl tartrates, -ribose, and -mannitol as chiral pool
starting materials. The key step was a tandem ring-closing/
cross-metathesis reaction in which lactone formation and
fragment coupling were accomplished in one pot. The spec-
troscopic data of synthetic product 2c were in agreement
with those reported for the natural product. Synargentolide
B isolated by Rivett et al. and the compound isolated by Per-
eda-Miranda et al. are not diastereomers, but rather they are
identical.
L
D
D
D
Introduction
Natural products containing α,β-unsaturated δ-lactone
moieties often show useful pharmacological properties, in-
cluding antitumor, antibacterial, and antigrowth effects.[1–4]
Synargentolides A–E (1–5) (Figure 1) are examples of such
lactones isolated by Rivett and Davies-Coleman et al. from
the South African genus Syncolostemon argenteus in 1998.[5]
The structures of five α-pyrones have been established based
on spectral, chiroptical, and chemical evidence. In 1990,
Pereda-Miranda and co-workers reported the isolation of
an α-pyrone, (6R)-[5R,6S-diacetyloxy-1S,2R-dihydroxy-3E-
heptenyl]-5,6-dihydro-2H-pyran-2-one (2c)[6] (Figure 2),
from another member of the family Lamiaceae, Hyptis ob-
longfolia. This compound was referred to as a diastereomer
of synargentolide B by Rivett et al. in their paper,[5] since it
was soluble in CDCl3, whereas synargentolide B isolated
from S. argenteus was found to be insoluble in CDCl3. The
structure of 2c was established based on the structure of 4-
deacetoxy-10-epi-olguine (6),[6] isolated from the same spe-
cies. Synargentolide B (2), (6R)-[5,6S-diacetyloxy-1,2-dihy-
droxy-3E-heptenyl]-5,6-dihydro-2H-pyran-2-one, has five
asymmetric carbons. A (6R)-configuration was assigned
based on the positive nǞπ* cotton effect in the CD spec-
trum. Rivett et al.[5] assigned the relative stereochemistry of
the diol at C-1Ј and C-2Ј as syn by preparation of an acet-
onide, but the absolute stereochemistry at C-1Ј, C-2Ј, and
C-5Ј has remained unassigned.
Figure 1. Synargentolides A–E isolated by Rivett et al.
On the basis of the structures assigned to 2 and 2c, and
our own structural revision (to 1b) of the originally pro-
posed structure (i.e., 1a) of synargentolide A,[7] we under-
took the synthesis of four diastereomers 2a–d differing in
their relative configurations at C-5Ј and C-6Ј using a tan-
dem ring-closing/cross-metathesis (RCM/CM) reaction as
the key step, promoted by the second-generation Hoveyda–
Grubbs catalyst.[8]
[a] Natural Products Chemistry Division, CSIR – Indian Institute
of Chemical Technology,
Hyderabad, A.P. 500007, India
Fax: +91-40-27160512
E-mail: gowravaramsr@yahoo.com
sabitha@iict.res.in
Homepage: http://www.iictindia.org/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300434.
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Synthesis of Synargentolide B and Its Stereoisomers
Figure 2. α,β-Unsaturated δ-lactones isolated by Pereda-Miranda
et al.
Results and Discussion
Our planned synthesis of the four isomers is summarized
retrosynthetically in Scheme 1. Thus, we planned to obtain
target compounds 2a–d from acyclic triene 9 in a one-pot
RCM/CM. It was anticipated that initial RCM of allyl acet-
ate 9 would provide six-membered lactone 8. A subsequent
CM reaction between olefinic fragments 7a–d and the exo-
cyclic olefin of 8 followed by acetonide hydrolysis would
provide target lactones 2a–d. Acyclic triene 9 would be ac-
cessible either from d-(–)-DET (diethyl tartrate) or d-
mannitol, and the other metathesis substrates 7a–d would
be accessible from l-(+)-DET, d-(–)-DET, and d-ribose.
Scheme 2. Synthesis of olefinic fragments 7a and 7d. DMAP = 4-
(dimethylamino)pyridine.
The synthesis of 7b and 7c started from d-ribose
(Scheme 3). Wittig reaction of ribose monoacetonide using
triphenylphosphonium methylide gave diol 13.[10] The diol
was then oxidatively cleaved with NaIO4, and the resulting
aldehyde was reduced with NaBH4 in MeOH to give
alcohol 14 in 90% yield. Olefinic fragment 7b was prepared
from 14 in four steps following the same reaction sequence
that was used for the preparation of 7a from 10a, i.e., tosyl-
ation, treatment with LiAlH4, acetonide hydrolysis, and fi-
nally acetylation.
Olefinic fragment 7c was accessible from alcohol 15,
which was prepared from d-ribose by known procedures.[11]
Alcohol 15 was converted into 7c in four steps following the
same reaction sequence that was used for the preparation of
Scheme 1. Retrosynthetic analysis of stereoisomers 2a–d.
Accordingly, the synthesis of olefinic coupling partner 7a 7a from 10a, i.e., tosylation, treatment with LiAlH4, aceton-
started from l-(+)-DET and is outlined in Scheme 2. ide hydrolysis, and finally acetylation.
Known alcohol 10a, which was prepared from l-(+)-DET
The synthesis of acyclic triene 9, a key intermediate
according to reported procedures,[9] was converted into 7a (Scheme 4) could be achieved starting from either d-(–)-
in four steps. Tosylation of 10a with TsCl gave an interme- DET or d-mannitol. Primary alcohol 10b, which was pre-
diate tosylate 11. On treatment with LiAlH4 in THF at 0– pared from d-(–)-DET (see Scheme 2), was oxidized with
60 °C, this tosylate was converted into a terminal methyl SO3·Py complex in DMSO/CH2Cl2 to give the correspond-
compound, which, without isolation, was subjected to acet- ing aldehyde. This aldehyde was then subjected to Keck
onide hydrolysis to give olefinic diol 12. Diol 12 was acet- asymmetric allylation[12] to give homoallylic alcohol 16 in
ylated with Ac2O in the presence of triethylamine to give 75% yield and with 97% de (determined by HPLC).[13]
olefinic fragment 7a in 92% yield. Olefinic fragment 7d was Acylation with acryloyl chloride gave acyclic triene 9 in
prepared from d-(–)-DET following the same reaction se- 88% yield. Compound 16 was also prepared from d-mann-
quence that was used for the preparation of 7a from l-(+)- itol. All of the chiral centers required for triene 9 are al-
DET (Scheme 2).
ready present in d-mannitol, whereas when compound 16
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G. Sabitha, K. Shankaraiah, J. S. Yadav
FULL PAPER
Scheme 3. Synthesis of olefinic fragments 7b and 7c.
Scheme 4. Synthesis of acyclic triene 9 from d-(–)-DET.
was prepared from DET, one chiral center had to be created which was exposed to K2CO3 in MeOH to give epoxide 18.
by Keck allylation. Diol 17 was prepared from d-mannitol Epoxide 18 was opened by vinylmagnesium bromide in the
in four steps following literature procedures[14] (Scheme 5). presence of catalytic CuI to give homoallylic alcohol 16,
Selective tosylation was achieved using TsCl and Et3N in and this compound was used for the preparation of acyclic
the presence of Bu2SnO to give an intermediate tosylate, triene 9. With substrates 7a–d and 9 in hand, the stage was
Scheme 5. Synthesis of acyclic triene 9 from d-mannitol.
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Synthesis of Synargentolide B and Its Stereoisomers
set for the evaluation of the key one-pot tandem RCM/ dem RCM/CM process. To our delight, the RCM/CM
CM[15] process for the synthesis of the target compounds.
tandem process between triene 9 and 7a (1.23:1) pro-
The first generation Grubbs catalyst proved incapable of ceeded smoothly in the presence of Hoveyda–Grubbs II cat-
effecting the RCM/CM in one pot, and instead, lactone 19, alyst 20 (10 mol-%) in refluxing benzene (Scheme 7), lead-
the product of RCM only, was formed in 90% yield. The ing to the formation of 21a. The lactone ring was formed
formation of the other possible cyclohexene derivative 19a in an RCM reaction, and a subsequent coupling occurred
was not observed (Scheme 6), and so the reaction was re- by a CM process in one pot. Similar procedures were car-
gioselective.
ried out for the coupling of 7b–d with 9 to deliver lactones
The second-generation Grubbs catalyst provided a mix- 21b–d in good yields. Compounds 21a–d were exposed to
ture of compound 19 as the major product and 21a as a TFA (trifluoroacetic acid) in CH2Cl2 for 12 h to remove the
minor product. We felt that the more reactive second-gener- acetonide and give the final target compounds (i.e., 2a–d;
ation Hoveyda–Grubbs catalyst 20 may promote the tan- Scheme 7).
Scheme 6.
Scheme 7. Synthesis of synargentolide B and its stereoisomers.
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G. Sabitha, K. Shankaraiah, J. S. Yadav
FULL PAPER
then added portionwise over 0.5 h, and then DMAP (0.007 g,
0.06 mmol) was added. The mixture was allowed to warm to room
temp. and stirred for 3 h. Then it was treated with HCl (1 n aq.;
2 mL) and extracted with CH2Cl2 (2ϫ15 mL). The combined or-
ganic extracts were washed with NaHCO3 (satd. aq.; 10 mL) and
H2O (10 mL). The organic phase was dried with anhydrous Na2SO4
and concentrated under reduced pressure. The residue was sub-
jected to silica gel column chromatography (EtOAc/hexane, 1:9) to
give 11 (0.375 g, 95%). [α]2D7 = –40.0 (c = 1.0, MeOH). IR (KBr):
The spectroscopic data of synthetic lactone 2a did not
match those reported for the natural product synargentol-
ide B, a compound isolated in 1998. The optical rotation
value for the natural product was reported as [α]2D7 = +45.6
(c = 1.2, MeOH), whereas synthetic product 2a showed
[α]2D7 = +51.5 (c = 0.5, MeOH). Neither did the physical
and analytical data of isomers 2b and 2d (both of which
were soluble in CDCl3) match the data of natural synargen-
tolide B. The observed optical rotation values for 2b and 2d
ν = 3458, 3079, 2987, 2934, 1624, 1376, 1246, 1216, 1057, 921,
˜
were [α]2D7 = +29.7 (c = 0.7, MeOH) and [α]D27 = +37.0 (c = 875 cm–1. H NMR (300 MHz, CDCl3): δ = 7.81 (d, J = 8.1 Hz, 2
1
H), 7.35 (d, J = 8.1 Hz, 2 H), 5.78 (m, 1 H), 5.30 (m, 2 H), 4.23
(t, J = 7.2 Hz, 1 H), 4.13 (m, 2 H), 3.85 (m, 1 H), 2.46 (s, 3 H),
1.39 (s, 3 H), 1.36 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
144.9, 134.2, 132.5, 129.8, 127.8, 119.5, 109.8, 78.7, 77.9, 67.9, 26.8,
26.5, 21.5 ppm. MS (ESI): m/z = 335 [M + Na]+. HRMS: calcd.
for C15H20O5SNa [M + Na]+ 335.0929; found 335.0934.
1.5, MeOH), respectively. Therefore, structures 2a, 2b and
2d were ruled out for natural synargentolide B. However,
the spectroscopic data (1H and 13C NMR) of synthetic
product 2c (soluble in CDCl3) {[α]2D7 = +25.6 (c = 0.7,
CHCl3)}, matched that of the natural product 6R-[5R,6S-
diacetyloxy-1S,2R-dihydroxy-3E-heptenyl]-5,6-dihydro-2H-
pyran-2-one (2c; soluble in CDCl3) {[α]2D5 = +28.8 (c = 0.18,
CHCl3)}, isolated by Pereda-Miranda et al. in 1990,[16] and
also matched the data of synargentolide B (2; insoluble in
CDCl3) isolated by Rivett et al. in 1998. Therefore, the
structures of the two isolated compounds, 2 and 2c, are
identical. The absolute stereochemistry of synargentolide B
was thus confirmed by its synthesis.
(2S,3S)-Pent-4-ene-2,3-diol (12):
A solution of 11 (0.35 g,
5.12 mmol) in dry THF (5 mL) was added dropwise to a stirred
suspension of LiAlH4 (0.083 g, 2.24 mmol) in dry THF (5 mL) at
0 °C. The reaction mixture was heated to 60 °C for 4 h, then it was
cooled to 0 °C, diluted with diethyl ether, and quenched by the
dropwise addition of Na2SO4 (satd. aq.). The solid material was
filtered and washed thoroughly several times with diethyl ether. The
combined organic extracts were dried with anhydrous Na2SO4. The
crude product was used in the next reaction without further purifi-
cation. HCl (3 n; 3 mL) was added, and the mixture was stirred at
room temp. for 6 h. After the reaction was complete, it was
quenched by the addition of NaHCO3 (satd. aq.), and the mixture
was extracted with EtOAc (2ϫ10 mL). The combined organic ex-
tracts were washed with H2O (5 mL) and brine (3 mL), dried
(Na2SO4), and concentrated under reduced pressure. The crude
product was purified by column chromatography (EtOAc/Hexanes,
3:7) to give compound 12 (0.074 g, 73% over two steps) as a color-
Conclusions
A tandem RCM/CM procedure was developed for rapid
access to functionalized lactones. This work presents a
highly efficient method for the preparation of synargentol-
ide B, which allowed the confirmation of its absolute stereo-
chemistry. The synthesis of other synargentolides is under
investigation in our laboratory.
less viscous liquid [α]2D7 = –27.0 (c = 0.8, MeOH). IR (KBr): ν =
˜
3383, 2978, 2886, 1645, 1374, 1037, 928 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 5.85 (m, 1 H), 5.37 (d, J = 17.3 Hz, 1 H), 5.25 (d, J
= 10.2 Hz, 1 H), 3.87 (t, J = 6.4 Hz, 1 H), 3.66 (m, 1 H), 2.41 (d,
J = 16.2 Hz, 1 H), 1.75 (br. s, 1 H), 1.20 (d, J = 6.4 Hz, 3 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 137.3, 117.23, 77.7, 70.5,
18.7 ppm. MS (EI): m/z = 102 [M]+.
Experimental Section
General Remarks: All reactions were performed under an inert at-
mosphere. All glassware used for reactions was oven/flame dried.
Anhydrous solvents were distilled prior to use: THF from Na and
benzophenone; CH2Cl2 and DMSO from CaH2; MeOH from Mg.
Commercially sourced reagents were used without purification.
Column chromatography was carried out using silica gel (60–
120 mesh) unless otherwise stated. Analytical thin layer chromatog-
raphy (TLC) was run on silica gel 60 F254 precoated plates (250 μm
thickness). Optical rotations [α]D were measured with a polarime-
ter. Infrared spectra were recorded in CHCl3 or using KBr (as
stated) and absorptions are reported in wavenumbers (cm–1). Mass
spectroscopic data were obtained using EI or ESI mass spectrome-
ters. High resolution mass spectra (HRMS; ESI+) were obtained
using either a TOF or a double-focusing spectrometer. 1H NMR
spectra were recorded at 300, 400, or 500 MHz, and 13C NMR
spectra at 75 MHz, in CDCl3 solution unless otherwise stated.
Chemical shifts are given in ppm downfield from tetramethylsilane,
and coupling constants (J) are reported in Hertz (Hz). The follow-
ing abbreviations are used to designate signal multiplicity: s singlet,
d doublet, t triplet, q quartet, quin quintet, m multiplet, br. broad.
(2S,3R)-1-(tert-Butyldimethylsilyloxy)-5-(4-methoxybenzyloxy)-2-
methylpentan-3-ol (12): Imidazole (3.96 g, 58.26 mmol) was added
to a stirred solution of diol 11 (7.4 g, 29.13 mmol) in CH2Cl2
(60 mL) at 0 °C, and the mixture was stirred for 15 min. tert-Butyl-
dimethylsilyl chloride (4.39 g, 29.13 mmol) was added to the reac-
tion mixture at 0 °C, and the resulting mixture was stirred for 1 h.
After TLC indicated that the reaction was complete, the reaction
mixture was concentrated under reduced pressure, and the residue
was purified by column chromatography (EtOAc/Hexane, 1:9) to
give pure product 12 (9.86 g, 92%) as a colorless liquid. [α]2D7 = +11
(c = 0.5, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.20 (d, J =
8.0 Hz, 2 H), 6.82 (d, J = 9.0 Hz, 2 H), 4.43 (s, 2 H), 3.78 (s, 3 H),
3.72–3.57 (m, 5 H), 3.55–3.48 (br. s, 1 H), 1.83–1.74 (m, 1 H), 1.73–
1.62 (m, 2 H), 0.9 (s, 9 H), 0.87 (d, J = 7.0 Hz, 3 H), 0.06 (s, 6 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 159.0, 130.3, 129.1, 113.6,
74.0, 72.7, 68.0, 67.3, 55.2, 40.1, 34.5, 25.7, 18.0, 13.3, –5.6,
–5.7 ppm. MS (ESI): m/z = 391 [M + Na]+.
[(4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]methyl
benzenesulfonate (11): Et3N (0.36 mL, 2.53 mmol) was added to a
solution of 10a (0.2 g, 1.26 mmol) in anhydrous CH2Cl2 (8 mL) at
4-Methyl-
(2S,3S)-Pent-4-ene-2,3-diyl diacetate (7a): Et3N (0.412 mL,
2.94 mmol), Ac2O (0.166 mL, 1.76 mmol), and DMAP (2 mg,
0.017 mmol) were added to diol 12 (0.060 g, 0.588 mmol) in dry
0 °C. 4-Methylbenzenesulfonyl chloride (0.24 g, 1.26 mmol) was CH2Cl2 (5 mL) at 0 °C, and the mixture was stirred at room temp.
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Synthesis of Synargentolide B and Its Stereoisomers
for 2 h. The mixture was diluted with CH2Cl2 (4 mL), washed with
H2O (4 mL) and brine (3 mL), dried with Na2SO4, and concen-
trated under reduced pressure. The crude product was purified by
column chromatography (EtOAc/hexane, 1:9) to give 7a (0.1 g,
added, the reaction mixture was partitioned between water and
CH2Cl2, and the aqueous phase was extracted with CH2Cl2. The
combined organic extracts were washed with water, dried with
Na2SO4, and concentrated in vacuo. The crude product was puri-
fied by column chromatography to give the tosylated compound
(1.63 g, 90 %) as a pale yellow oil. Solid K2 CO3 (1.93 g,
14.03 mmol) was added to a solution of the tosylated compound
(1.6 g, 4.67 mmol) in methanol (15 mL) at room temp., and the
mixture was stirred for 6 h. The solids were removed by filtration.
The filtrate was diluted with water and extracted with diethyl ether
(3 ϫ 15 mL). The combined organic extracts were washed with
brine, dried with Na2SO4, and concentrated under reduced pres-
sure. The residue was purified by column chromatography to give
18 (0.636 g, 80%) as a colorless oil. [α]2D7 = +11.0 (c = 1.0, MeOH).
92%) as a colorless liquid. [α]2D7 = –32.6 (c = 0.5, MeOH). IR (KBr):
1
ν = 2986, 1742, 1373, 1227, 1025, 928 cm–1. H NMR (300 MHz,
˜
CDCl3): δ = 5.76 (m, 1 H), 5.32 (m, 3 H), 5.05 (m, 1 H), 2.10 (s, 3
H), 2 . 05 (s, 3 H), 1 . 2 1 ( d , J = 6. 6 H z , 3 H ) p p m . 1 3 C
NMR (75 MHz, CDCl3): δ = 170.2, 169.8, 132.2, 119.1, 75.4, 70.2,
20.9, 20.8, 15.9 ppm. MS (ESI): m/z = 185 [M– H]+. HRMS: calcd.
for C9H13O4 [M– H]+ 185.0808; found 185.0805.
[(4R,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]methanol (14):
NaIO4 (0.682 g, 3.19 mmol) was added to an ice-cooled solution of
13 (0.5 g, 2.65 mmol) in H2O (5.0 mL) and THF (10 mL), and the
mixture was stirred at room temperature for 1 h. The mixture was
then concentrated in vacuo, and the residue was partitioned be-
tween H2O and Et2O. The organic phase was washed with brine
and dried with Na2SO4, and the solvents were evaporated in vacuo
to give the aldehyde (0.33 g, 80%) as a colorless oil that was used
in the next step without further purification. NaBH4 (0.145 g,
3.8 mmol) was added to an ice-cooled solution of the aldehyde ob-
tained above (0.30 g, 1.92 mmol) in MeOH (10 mL), and the mix-
ture was stirred at 0 °C for 0.5 h. The mixture was then concen-
trated in vacuo, and the residue was partitioned between H2O and
EtOAc. The organic phase was washed with brine and dried with
Na2SO4, the solvent was evaporated, and the residue was purified
by column chromatography (EtOAc/hexanes, 2:9) to give 14
(0.273 g, 90%) as a colorless oil. [α]2D7 = +43.4 (c = 0.5, CHCl3).
IR (KBr): ν = 2989, 2934, 1655, 1376, 1247, 1218, 1058, 871 cm–1.
˜
1H NMR (300 MHz, CDCl3): δ = 5.85 (ddd, J = 17.2, 10.2, 6.7 Hz,
1 H), 5.44 (dt, J = 17.2, 1.3 Hz, 1 H), 5.30 (dt, J = 10.3, 1.1 Hz, 1
H), 4.37 (dd, J = 7.2, 6.4 Hz, 1 H), 3.61 (dd, J = 7.9, 4.9 Hz, 1 H),
3.10 (m, 1 H), 2.83 (t, J = 4.9 Hz, 1 H), 2.72 (dd, J = 4.9, 2.6 Hz,
1 H), 1.45 (s, 3 H), 1.44 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 134.8, 118.9, 109.7, 80.1, 80.0, 51.1, 46.6, 26.8, 26.6 ppm. MS
(ESI): m/z = 193 [M + Na]+. HRMS: calcd. for C9H14O3Na [M +
Na]+ 193.0840; found 193.0838.
[(4R,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]methanol (10b):
The procedure was same as that described in ref.[10] [α]2D7 = +3.9 (c
= 1.0, CHCl ). IR (KBr): ν = 3459, 2987, 2932, 1642, 1376, 1056,
˜
3
873 cm–1. 1H NMR (300 MHz, CDCl3): δ = 5.83 (ddd, J = 17.2,
10.2, 7.5 Hz, 1 H), 5.38 (d, J = 17.2 Hz, 1 H), 5.26 (d, J = 10.2 Hz,
1 H), 4.30 (m, 1 H), 3.82 (m, 2 H), 3.60 (m, 1 H), 2.01 (br. s, 1 H),
1.43 (s, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 134.9, 118.8,
109.0, 81.1, 78.2, 60.6, 26.7, 26.7 ppm. MS (EI): m/z = 158 [M]+.
IR (KBr): ν = 3460, 2985, 2932, 1647, 1374, 1226, 918, 873 cm–1.
˜
1H NMR (600 MHz, CDCl3): δ = 5.87 (ddd, J = 17.4, 10.4, 7.1 Hz,
1 H), 5.40 (dt, J = 17.4, 1.4 Hz, 1 H), 5.28 (dt, J = 10.4, 1.4 Hz, 1
H), 4.65 (m, 1 H), 4.27 (m, 1 H), 3.59 (m, 2 H), 2.09 (br. s, 1 H),
1.52 (s, 3 H), 1.40 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
133.2, 119.1, 109.1, 78.5, 78.5, 62.2, 28, 25.4 ppm. MS (EI): m/z =
158 [M]+.
(R)-1-[(4R,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]but-3-en-1-ol
(16)
Procedure I: SO3·pyridine complex (5.03 g, 31.64 mmol) and then
triethylamine (4.45 mL, 31.64 mmol) were added to a solution of
primary alcohol 10b (1.0 g, 6.23 mmol) in dry CH2Cl2 (13 mL) at
–10 °C. After 5 min, dry DMSO (10 mL, 10 mmol) was added, and
the mixture was stirred for 15 min. Then the reaction was quenched
by the addition of brine (10 mL), and the mixture was diluted with
CH2Cl2 (20 mL). The organic phase was separated and washed
with NaHCO3 (satd. aq.; 2ϫ15 mL). The organic phase was dried
with anhydrous Na2SO4, filtered, and concentrated in vacuo. The
residue was subjected to flash column chromatography (EtOAc/
hexane, 1:9) to give the pure aldehyde (0.908 g, 92%) as a pale
yellow oil. This aldehyde was used in the next reaction without any
characterization. A mixture of (R,R)-BINOL (0.16 g, 0.57 mmol)
and Ti(OiPr)4 (0.17 mL, 0.57 mmol) in dry CH2Cl2 (8.0 mL) was
stirred under reflux in the presence of 4 Å molecular sieves (1.0 g).
After 1 h, the mixture was cooled to room temperature, and the
aldehyde (0.5 g, 6.9 mmol) in CH2Cl2 (6.0 mL) was added. The
mixture was stirred for a further 10 min. The reaction mixture was
then cooled to –78 °C, and allyltri-n-butyltin (2.16 mL, 6.92 mmol)
was added. The resulting mixtre was stirred further at –20 °C for
24 h. NaHCO3 (satd. aq.; 15.0 mL) was added to quench the reac-
tion. The mixture was stirred for a further 30 min, after which, it
was extracted with CH2Cl2 (2ϫ30 mL). The organic phase was
washed with water (10 mL) and dried with Na2SO4, the solvent was
evaporated, and the residue was purified by column chromatog-
raphy (EtOAc/hexanes, 1:9) to give 16 (0.856 g, 75%) as a colorless
oil.
(2R,3S)-Pent-4-ene-2,3-diyl Diacetate (7b): The procedure was
same as that described for the preparation of 7a. [α]2D7 = +8.2 (c =
0.5, MeOH). IR (KBr): ν = 2985, 1742, 1375, 1246, 1026, 775 cm–1.
˜
1H NMR (300 MHz, CDCl3): δ = 5.80 (m, 1 H), 5.33 (m, 3 H),
5.08 (m, 1 H), 2.10 (s, 3 H), 2.04 (s, 3 H), 1.21 (d, J = 6.8 Hz, 3
H). 13C NMR (75 MHz, CDCl3): δ = 169.9, 169.5, 131.8, 118.9,
75.2, 70.1, 20.7, 20.6, 14.5 ppm. MS (ESI): m/z = 185 [M– H]+.
(2S,3R)-Pent-4-ene-2,3-diyl Diacetate (7c): The procedure was same
as that described for the preparation of 7a. [α]2D7 = –10.2 (c = 0.8,
MeOH). IR (KBr): ν = 2986, 1742, 1375, 1246, 1026, 775 cm–1. 1H
˜
NMR (300 MHz, CDCl3): δ = 5.80 (m, 1 H), 5.34 (m, 3 H), 5.08
(m, 1 H), 2.10 (s, 3 H), 2.04 (s, 3 H), 1.21 (d, J = 6.8 Hz, 3 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 169.9, 169.5, 131.8, 118.9,
75.2, 70.1, 20.7, 20.6, 14.5 ppm. MS (ESI): m/z = 209 [M + Na]+.
(2R,3R)-Pent-4-ene-2,3-diyl Diacetate (7d): The procedure was
same as that described for the preparation of 7a. [α]2D7 = +37.2 (c
= 1.0, MeOH). IR (KBr): ν = 2985, 1743, 1373, 1227, 1025,
˜
925 cm–1. 1H NMR (300 MHz, CDCl3): δ = 5.76 (m, 1 H), 5.31
(m, 3 H), 5.05 (m, 1 H), 2.10 (s, 3 H), 2.05 (s, 3 H), 1.21 (d, J =
6.6 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.2, 169.8,
132.2, 119.1, 75.4, 70.2, 20.9, 20.8, 16.0 ppm. MS (ESI): m/z = 185
[M– H]+.
(4S,5R)-2,2-Dimethyl-4-[(R)-oxiran-2-yl]-5-vinyl-1,3-dioxolane (18):
A solution of diol 17 (1.0 g, 5.31 mmol) in dry CH2Cl2 (15 mL)
was cooled to 0 °C and treated with TsCl (1.01 g, 5.31 mmol) fol-
lowed by Et3N (2.23 mL, 16.1 mmol). The mixture was stirred at
room temp. for 3 h. After the reaction was complete, water was
Procedure II: A round-bottomed flask was charged with copper(I)
iodide (0.067 g, 0.35 mmol), gently heated under vacuum, and then
Eur. J. Org. Chem. 2013, 4870–4878
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4875

G. Sabitha, K. Shankaraiah, J. S. Yadav
FULL PAPER
slowly cooled under a flow of N2. Dry THF (20 mL) was then
added, the resulting suspension was cooled to –40 °C, and stirred
while vinylmagnesium bromide (1 m in THF; 4.23 mL, 4.23 mmol)
was added. A solution of 18 (0.6 g, 3.52 mmol) in THF (10 mL)
was added, and the resulting mixture was stirred at –40 °C for 1 h,
and then at room temp. for 2 h. After the starting material had
been consumed, the mixture was quenched with NH4Cl (satd. aq.).
The aqueous phase was extracted with EtOAc, and the combined
organic extracts were washed with brine, dried with Na2SO4, and
concentrated in vacuo. The residue was purified by column
chromatography on silica gel (EtOAc/hexane, 1:9) to give 16
(0.559 g, 80%) as a colorless oil. [α]2D7 = +135 (c = 1.0, MeOH). IR
26.8, 25.7 ppm. MS (ESI): m/z = 225 [M + H]+. HRMS: calcd. for
C12H17O4 [M + H]+ 225.1121; found 225.1117.
(2S,3S,E)-5-{(4R,5R)-2,2-Dimethyl-5-[(R)-6-oxo-3,6-dihydro-2H-
pyran-2-yl]-1,3-dioxolan-4-yl}pent-4-ene-2,3-diyl Diacetate (21a):
Second generation Hoveyda–Grubbs catalyst 20 (0.0101 g,
0.016 mmol) in benzene was added by cannula to olefin 7a (0.03 g,
0.16 mmol) and triene 9 in anhydrous benzene in a flask fitted with
a condenser. The mixture was stirred for 0.5 h at room temperature,
and then it was heated at reflux under argon for 1–2 h. The pro-
gress of the reaction was monitored by TLC. After the reaction
was complete, the solvent was removed under reduced pressure, and
the product was purified directly by silica gel column chromatog-
raphy (EtOAc/hexane, 3:7) to give 21a (0.0542 g, 88%) as a color-
(KBr): ν = 3458, 3079, 2987, 2934, 1624, 1376, 1246, 1216, 1057,
˜
1
921, 875 cm–1. H NMR (300 MHz, CDCl3): δ = 5.93–5.79 (m, 2
less liquid. [α]2D7 = +43.6 (c = 0.6, MeOH). IR (KBr): ν = 2986,
˜
H), 5.43 (d, J = 17.3 Hz, 1 H), 5.26 (d, J = 10.1 Hz, 1 H), 5.15 (m,
2 H), 4.47 (t, J = 7.9 Hz, 1 H), 3.87 (m, 1 H), 3.75 (dd, J = 7.9,
4.5 Hz, 1 H), 2.28 (m, 2 H), 2.20 (d, J = 3.0 Hz, 1 H), 1.44 (s, 3
H), 1.42 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 136.4,
134.0, 118.0, 117.8, 108.8, 82.4, 78.2, 70.4, 37.2, 26.8, 26.7 ppm.
MS (ESI): m/z = 221 [M + Na]+. HRMS: calcd. for C11H18O3Na
[M + Na]+ 221.1153; found 221.1161.
2929, 1738, 1374, 1230, 1162, 1065, 815 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 6.89 (dt, J = 9.9, 4.9 Hz, 1 H), 6.02 (dt, J = 9.9, 1.1 Hz,
1 H), 5.92 (dd, J = 15.9, 6.0 Hz, 1 H), 5.82 (dd, J = 15.9, 6.0 Hz,
1 H), 5.34 (dd, J = 6.0, 5.0 Hz, 1 H), 5.03 (m, 1 H), 4.47 (dd, J =
8.0, 7.0 Hz, 1 H), 4.43 (m, 1 H), 3.85 (dd, J = 8.0, 7.0 Hz, 1 H),
2.54 (m, 2 H), 2.10 (s, 3 H), 2.05 (s, 3 H), 1.42 (s, 3 H), 1.42 (s, 3
H), 1.20 (d, J = 6.0 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 170.2, 169.9, 162.5, 144.5, 132.1, 127.3, 121.3, 110.2, 80.7, 79.2,
77.9, 74.4, 70.5, 26.8 (2 C), 26.2, 21.0, 20.9, 16.1 ppm. MS (ESI):
m/z = 400 [M + NH4]+. HRMS: calcd. for C19H30O8N [M +
NH4]+ 400.1965; found 400.1960.
(R)-1-[(4R,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]but-3-enyl
Acrylate (9): Acryloyl chloride (0.35 mL, 4.44 mmol) was added
dropwise to a solution of alcohol 16 (0.8 g, 4.04 mmol), Et3N
(1.4 mL, 10.1 mmol), and DMAP (cat.) in anhydrous CH2Cl2
(15 mL) at 0 °C under N2. The mixture was allowed to reach room
temp. and it was stirred for 1 h. After the reaction was complete,
the mixture was diluted with CH2Cl2 (15 mL), and washed with
brine (10 mL) and NaHCO3 (aq.). The aqueous phases were ex-
tracted with CH2Cl2 (2ϫ15 mL). The combined organic extracts
were washed with HCl (1 m aq.; 2 mL) and brine (3 mL), dried
with Na2SO4, and concentrated under reduced pressure. The crude
product was purified by column chromatography (EtOAc/hexane,
1:19) to give pure acrylate 9 (0.896 g, 88%) as a pale yellow liquid.
(2R,3S,E)-5-{(4R,5R)-2,2-Dimethyl-5-[(R)-6-oxo-3,6-dihydro-2H-
pyran-2-yl]-1,3-dioxolan-4-yl}pent-4-ene-2,3-diyl Diacetate (21b):
The procedure was same as that described for the preparation of
21a. [α]2D7 = +38.0 (c = 0.79, MeOH). IR (KBr): ν = 2988, 2936,
˜
1
1738, 1375, 1237, 1067, 816 cm–1. H NMR (300 MHz, CDCl3): δ
= 6.90 (m, 1 H), 6.03 (dt, J = 10.0, 1.7 Hz, 1 H), 5.88 (m, 2 H),
5.41 (dd, J = 5.3, 3.5 Hz, 1 H), 5.08 (m, 1 H), 4.47 (m, 2 H), 3.86
(t, J = 7.3 Hz, 1 H), 2.54 (m, 2 H), 2.10 (s, 3 H), 2.04 (s, 3 H), 1.44
(s, 3 H), 1.43 (s, 3 H), 1.21 (d, J = 6.4 Hz, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 170.3, 170.0, 162.5, 144.5, 132.0, 127.1,
121.4, 110.2, 80.8, 79.2, 77.9, 74.3, 70.4, 26.9 (2 C), 26.2, 21.1, 21.0,
15.9 ppm. MS (ESI): m/z = 405 [M + Na]+. HRMS: calcd. for
[α]2D7 = +20.0 (c = 1.0, MeOH). IR (KBr): ν = 3081, 2987, 1728,
˜
1
1639, 1406, 1376, 1261, 1188, 1063, 986, 926, 875 cm–1. H NMR
(300 MHz, CDCl3): δ = 6.40 (d, J = 17.3 Hz, 1 H), 6.09 (dd, J =
17.3, 10.5 Hz, 1 H), 5.79 (m, 3 H), 5.35 (d, J = 17.3 Hz, 1 H), 5.22 C19H26O8Na [M + Na]+ 405.1519; found 405.1512.
(m, 2 H), 5.09 (m, 2 H), 4.35 (t, J = 7.5 Hz, 1 H), 3.85 (dd, J =
(2S,3R,E)-5-{(4R,5R)-2,2-Dimethyl-5-[(R)-6-oxo-3,6-dihydro-2H-
7.5, 6.0 Hz, 1 H), 2.51 (m, 1 H), 2.41 (m, 1 H), 1.42 (s, 3 H), 1.41
pyran-2-yl]-1,3-dioxolan-4-yl}pent-4-ene-2,3-diyl Diacetate (21c):
(s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 165.2, 135.4, 132.8,
The procedure was same as that described for the preparation of
131.1, 128.1, 118.8, 118.1, 109.4, 80.5, 79.7, 72.3, 35.9, 26.8,
21a. [α]2D7 = +45.5 (c = 0.46, MeOH). IR (KBr): ν = 2987, 2926,
˜
26.7 ppm. MS (ESI): m/z = 275 [M + Na]+. HRMS: calcd. for
1
1737, 1375, 1235, 1066, 976 cm–1. H NMR (300 MHz, CDCl3): δ
C14H20O4Na [M + Na]+ 275.1253; found 275.1248.
= 6.92 (dt, J = 9.8, 4.5 Hz, 1 H), 6.04 (dt, J = 9.8, 1.5 Hz, 1 H),
5.87 (m, 2 H), 5.41 (dd, J = 6.0, 3.7 Hz, 1 H), 5.07 (dq, J = 6.8,
(R)-6-[(4R,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]-5,6-dihydro-
3.7 Hz, 1 H), 4.49 (dd, J = 6.8, 3.8 Hz, 1 H), 4.44 (m, 1 H), 3.89
2H-pyran-2-one (19): first generation Grubbs catalyst (0.008 g,
(t, J = 6.8 Hz, 1 H), 2.54 (m, 2 H), 2.09 (s, 3 H), 2.05 (s, 3 H), 1.43
010 mmol) in benzene was added by cannula to olefin 7a (1 equiv.,
(s, 6 H), 1.21 (d, J = 6.8 Hz, 3 H) ppm. 13C NMR (75 MHz,
0.03 g, 0.16 mmol) and triene 9 (1.23 equiv., 0.05 g, 0.198 mmol) in
CDCl3): δ = 170.4, 169.9, 162.6, 144.6, 132.4, 127.3, 121.4, 110.3,
anhydrous benzene in a flask fitted with a condenser. The reaction
80.8, 79.1, 77.9, 74.5, 70.6, 26.9 (2 C), 26.2, 21.1, 21.0, 15.0 ppm.
mixture was heated at reflux under argon for 1–2 h. The progress
MS (ESI): m/z = 400 [M + NH4]+. HRMS: calcd. for C19H30O8N
of the reaction was monitored by TLC. After the reaction was com-
[M + NH4]+ 400.1965; found 400.1959.
plete, the solvent was removed under reduced pressure, and the
crude product was purified directly by silica gel column chromatog-
(2R,3R,E)-5-{(4R,5R)-2,2-Dimethyl-5-[(R)-6-oxo-3,6-dihydro-2H-
pyran-2-yl]-1,3-dioxolan-4-yl}pent-4-ene-2,3-diyl Diacetate (21d):
The procedure was same as that described for the preparation of
raphy (EtOAc/hexane, 3:7) to give 19 (0.0408 g, 92%) as a colorless
liquid. [α]2D7 = +3.7 (c = 1.1, MeOH). IR (KBr): ν = 2987, 2931,
˜
1733, 1639, 1377, 1242, 1066, 813 cm–1
.
1H NMR (600 MHz, 21a. [α]2D7 = +76.0 (c = 0.39, MeOH). IR (KBr): ν = 2987, 2930,
˜
CDCl3): δ = 5.92 (ddd, J = 9.8, 5.2, 3.0 Hz, 1 H), 6.04 (dt, J = 9.8, 1739, 1376, 1230, 1167, 1065, 976, 815 cm–1. H NMR (300 MHz,
1
1.1 Hz, 1 H), 5.96 (ddd, J = 16.9, 10.5, 6.8 Hz, 1 H), 5.45 (d, J =
16.9 Hz, 1 H), 5.29 (d, J = 10.5 Hz, 1 H), 4.48 (quin, J = 5.6 Hz,
1 H), 4.44 (t, J = 6.8 Hz, 1 H), 3.92 (t, J = 6.8 Hz, 1 H), 2.55 (m,
CDCl3): δ = 6.92 (dt, J = 9.8, 4.5 Hz, 1 H), 6.04 (dt, J = 9.8, 1.5 Hz,
1 H), 5.86 (m, 2 H), 5.35 (t, J = 6.0 Hz, 1 H), 5.05 (m, 1 H), 4.49
(m, 1 H), 4.44 (m, 1 H), 3.87 (t, J = 6.8 Hz, 1 H), 2.53 (m, 2 H),
2 H), 1.44 (s, 3 H), 1.43 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): 2.09 (s, 3 H), 2.05 (s, 3 H), 1.425 (s, 3 H), 1.427 (s, 3 H), 1.22 (d,
δ = 162.8, 144.7, 135.1, 121.2, 118.1, 109.9, 80.6, 79.9, 77.6, 26.9,
J = 6.8 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 170.1,
4876
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 4870–4878

Synthesis of Synargentolide B and Its Stereoisomers
169.7, 162.5, 144.5, 132.3, 127.6, 121.3, 110.3, 80.8, 78.9, 77.9, 74.5,
1.5 Hz, 1 H), 5.88 (dd, J = 15.6, 5.0 Hz, 1 H), 5.79 (dd, J = 15.6,
6.0 Hz, 1 H), 5.31 (dd, J = 6.0, 3.8 Hz, 1 H), 5.05 (dq, J = 6.6,
70.3, 26.9, 26.8, 26.2, 21.0, 20.9, 16.0 ppm. MS (ESI): m/z = 405
[M + Na]+. HRMS: calcd. for C19H26O8Na [M + Na]+ 405.1519; 3.8 Hz, 1 H), 4.53 (m, 1 H), 4.48 (m, 1 H), 3.70 (dd, J = 6.9, 2.6 Hz,
found 405.1511.
1 H), 2.57 (m, 2 H), 2.08 (s, 3 H), 2.04 (s, 3 H), 1.20 (d, J = 6.6 Hz,
3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.5, 170.3, 163.7,
145.8, 134.2, 126.7, 120.9, 76.8, 74.9, 74.3, 70.5, 69.5, 25.5, 21.1,
21.1, 15.1 ppm. [α]2D7 = +22.7 (c = 0.7, MeOH). 1H NMR
(500 MHz, CD3OD): δ = 7.07 (m, 1 H), 6.00 (m, 1 H), 5.95 (m, 1
H), 5.80 (ddd, J = 15.6, 6.6, 1.3 Hz, 1 H), 5.41 (dd, J = 6.8, 3.4 Hz,
1 H), 5.07 (dq, J = 6.6, 3.4 Hz, 1 H), 4.55 (m, 1 H), 4.35 (dd, J =
4.5, 3.4 Hz, 1 H), 3.67 (dd, J = 6.6, 3.4 Hz, 1 H), 2.58 (m, 2 H),
2.08 (s, 3 H), 2.05 (s, 3 H), 1.22 (d, J = 6.6 Hz, 3 H) ppm. 13C
NMR (75 MHz, CD3OD): δ = 172.1, 171.8, 166.3, 148.6, 136.4,
126.6, 121.1, 78.9, 76.1, 75.6, 72.0, 71.3, 26.3, 21.2, 21.1, 15.2 ppm.
MS (ESI): m/z = 360 [M + NH4]+. HRMS: calcd. for C16H26O8N
[M + NH4]+ 360.1652; found 360.1650.
(2S,3S,6R,7S,E)-6,7-Dihydroxy-7-[(R)-6-oxo-3,6-dihydro-2H-pyran-
2-yl]hept-4-ene-2,3-diyl Diacetate (2a): Compound 21a (0.03 g,
0.078 mmol) was dissolved in dry CH2Cl2 (5 mL), and TFA
(0.024 mL, 0.31 mmol) was added at 0 °C. The reaction mixture
was stirred at that temperature for 12 h, then the reaction mixture
was diluted with CH2Cl2 (10 mL) and quenched by the addition of
NaHCO3 (satd. aq.; 8 mL). The mixture was extracted with CH2Cl2
(2ϫ15 mL), and the combined organic extracts were washed with
brine (8 mL) and concentrated under reduced pressure. The residue
was subjected to column chromatography (EtOAc/hexane, 6:4) to
give pure diol 2a (0.023 g, 88%) as a colorless gummy liquid. [α]
27 = +51.5 (c = 0.5, MeOH). IR (neat): ν = 3446, 2925, 1731, 1381,
˜
D
1238, 1059, 978, 818 cm–1. 1H NMR (300 MHz, CD3OD): δ = 6.94
(ddd, J = 9.6, 5.3, 3.1 Hz, 1 H), 6.03 (dt, J = 9.6, 2.1 Hz, 1 H),
5.87 (dd, J = 15.0, 5.3 Hz, 1 H), 5.77 (dd, J = 15.0, 6.4 Hz, 1 H),
5.34 (dd, J = 6.4, 5.3 Hz, 1 H), 5.08 (m, 1 H), 4.51 (m, 1 H), 4.49
(m, 1 H), 3.70 (dd, J = 4.2, 2.1 Hz, 1 H), 2.56 (m, 2 H), 2.33 (br.
s, 1 H), 2.10 (s, 3 H), 2.06 (s, 3 H), 1.21 (d, J = 6.5 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.6, 170.1, 163.6, 145.7, 133.6,
127.3, 121.0, 76.9, 74.8, 74.2, 70.6, 69.4, 25.5, 21.1, 21.0, 16.1 ppm.
1H NMR (500 MHz, CD3OD): δ = 7.00 (dt, J = 9.6, 4.3 Hz, 1 H),
6.02 (dt, J = 9.8, 1.8 Hz, 1 H), 5.89 (dd, J = 15.6, 5.6 Hz, 1 H),
5.73 (ddd, J = 15.6, 6.6, 1.3 Hz, 1 H), 5.30 (t, J = 6.1 Hz, 1 H),
5.04 (m, 1 H), 4.52 (td, J = 8.9, 6.8 Hz, 1 H), 4.36 (m, 1 H), 3.65
(dd, J = 6.8, 3.0 Hz, 1 H), 2.57 (m, 2 H), 2.10 (s, 3 H), 2.07 (s, 3
H), 1.22 (d, J = 6.6 Hz, 3 H) ppm. 13C NMR (75 MHz, CD3OD):
δ = 172.1, 171.7, 166.3, 148.6, 136.4, 127.1, 121.1, 78.9, 76.5, 75.4,
72.0, 71.3, 26.3, 21.1, 21.0, 16.4 ppm. MS (ESI): m/z = 365 [M +
Na]+. HRMS: calcd. for C16H22O8Na [M + Na]+ 365.1206; found
365.1201.
(2R,3R,6R,7S,E)-6,7-Dihydroxy-7-[(R)-6-oxo-3,6-dihydro-2H-
pyran-2-yl]hept-4-ene-2,3-diyl Diacetate (2d): The procedure was
same as that described for the preparation of 2a. Colorless gummy
liquid. [α]2D7 = +37.0 (c = 1.5, MeOH). IR (neat): ν = 3426, 2925,
˜
1738, 1376, 1235, 1066, 976, 815 cm–1. 1H NMR (500 MHz,
CDCl3): δ = 6.95 (dt, J = 9.8, 4.2 Hz, 1 H), 6.01 (dt, J = 9.8, 1.8 Hz,
1 H), 5.87 (dd, J = 15.7, 5.3 Hz, 1 H), 5.74 (dd, J = 15.7, 6.4 Hz,
1 H), 5.27 (dd, J = 6.0, 5.4 Hz, 1 H), 5.05 (m, 1 H), 4.50 (m, 1 H),
4.45 (m, 1 H), 3.68 (dd, J = 6.8, 3.0 Hz, 1 H), 3.00 (br. s, 1 H),
2.55 (m, 2 H), 2.08 (s, 3 H), 2.04 (s, 3 H), 1.20 (d, J = 6.6 Hz, 3 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 170.4, 170.2, 163.6, 145.6,
133.9, 127.2, 121.0, 76.9, 75.0, 74.3, 70.3, 69.5, 25.5, 21.1, 21.0,
16.1 ppm. 1H NMR (500 MHz, CD3OD): δ = 7.00 (dt, J = 9.8,
4.3 Hz, 1 H), 5.86 (m, 2 H), 5.67 (ddd, J = 15.6, 6.8, 1.2 Hz, 1 H),
5.25 (dd, J = 7.0, 6.2 Hz, 1 H), 4.94 (m, 1 H), 4.44 (td, J = 8.8,
6.6 Hz, 1 H), 4.20 (t, J = 4.5 Hz, 1 H), 3.57 (dd, J = 6.3, 3.8 Hz, 1
H), 2.47 (m, 2 H), 1.99 (s, 3 H), 1.95 (s, 3 H), 1.12 (d, J = 6.6 Hz,
3 H) ppm. 13C NMR (75 MHz, CD3OD): δ = 172.2, 171.9, 166.5,
148.7, 136.4, 127.3, 121.1, 79.0, 76.6, 75.7, 72.1, 71.6, 26.3, 21.0,
20.9, 16.4 ppm. MS (ESI): m/z = 360 [M + NH4]+. HRMS: calcd.
for C16H26O8N [M + NH4]+ 360.1652; found 360.1647.
(2R,3S,6R,7S,E)-6,7-Dihydroxy-7-[(R)-6-oxo-3,6-dihydro-2H-pyran-
2-yl]hept-4-ene-2,3-diyl Diacetate (2b): The procedure was same as
that described for the preparation of 2a. Colorless gummy liquid.
[α]2D7 = +29.7 (c = 0.7, MeOH). IR (KBr): ν = 3421, 2925, 1734,
Supporting Information (see footnote on the first page of this arti-
˜
cle): Copies of the 1H and 13C NMR spectra of all new compounds.
1375, 1238, 1064, 1028, 975, 818 cm–1
.
1H NMR (300 MHz,
CDCl3): δ = 6.95 (dt, J = 9.8, 4.2 Hz, 1 H), 6.01 (dt, J = 9.8, 1.0 Hz,
1 H), 5.86 (dd, J = 15.6, 5.3 Hz, 1 H), 5.79 (dd, J = 15.6, 6.4 Hz,
1 H), 5.34 (dd, J = 6.4, 3.8 Hz, 1 H), 5.05 (m, 1 H), 4.51 (dd, J =
15.1, 7.5 Hz, 1 H), 4.45 (m, 1 H), 3.69 (dd, J = 6.6, 3.0 Hz, 1 H),
3.10 (br. s, 1 H), 2.55 (m, 2 H), 2.07 (s, 3 H), 2.03 (s, 3 H), 1.19 (d,
J = 6.6 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.5,
170.1, 163.7, 145.7, 133.9, 126.7, 120.9, 77.0, 74.8, 74.3, 70.5, 69.6,
25.4, 21.1, 21.0, 15.1 ppm. 1H NMR (500 MHz, CD3OD): δ = 7.06
(m, 1 H), 6.01 (dt, J = 9.8, 1.8 Hz, 1 H), 5.94 (ddd, J = 15.7, 5.8,
0.9 Hz, 1 H), 5.80 (ddd, J = 15.7, 6.8, 1.2 Hz, 1 H), 5.40 (dd, J =
6.6, 3.4 Hz, 1 H), 5.04 (dq, J = 6.7, 3.4 Hz, 1 H), 4.56 (td, J = 6.6,
2.5 Hz, 1 H), 4.36 (m, 1 H), 3.67 (dd, J = 6.8, 3.4 Hz, 1 H), 2.58
(m, 2 H), 2.09 (s, 3 H), 2.04 (s, 3 H), 1.22 (d, J = 6.6 Hz, 3 H)
ppm. 13C NMR (125 MHz, CD3OD): δ = 171.9, 171.5, 165.9,
147.9, 136.1, 126.2, 121.0, 78.4, 75.9, 75.1, 71.7, 70.9, 26.1, 21.2,
21.1, 15.3 ppm. MS (ESI): m/z = 365 [M + Na]+. HRMS: calcd.
for C16H22O8Na [M + Na]+ 365.1206; found 365.1200.
Acknowledgments
K. S. thanks the Council of Scientific and Industrial Research
(CSIR), New Delhi, for the award of a fellowship.
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˜
3
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1
CDCl3): δ = 6.95 (ddd, J = 9.8, 5.2, 3.5 Hz, 1 H), 6.02 (dt, J = 9.8,
Eur. J. Org. Chem. 2013, 4870–4878
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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[16] Dr. Rogelio Pereda-Miranda (from Mexico) expressed his in-
ability to provide any spectra of the isolated compound when
contacted in 2012, when he lived in NYC and worked as a
Fulbright Scholar at Lehman College at that time. The authors
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man from Rhodes University, South Africa had earlier pro-
1
vided us with the H NMR spectrum of synargentolide A, but
we could not get a reply from him about synargentolide B.
Received: March 24, 2013
Published Online: June 19, 2013
4878
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 4870–4878