Synthesis of butenolides recently isolated from marine microorganisms

Article abstract of DOI:10.1016/j.tetlet.2007.08.123

The syntheses and ¹³C NMR analyses of four diastereomeric butenolides, two of which were recently isolated from the marine microorganisms Streptomycete B 5632 and Streptoverticillium luteoverticillatum 11014 are described. The two isolated butenolides were found to be one of the two diastereomers (4S,10R^*,11R^*)-4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olide (RRS-1 or SSS-1) and one of the two diastereomers (4S,10S^*,11R^*)-4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olide (SRS-1 or RSS-1). An asymmetric 1,3-dipolar cycloaddition of a thiocarbonyl ylide with a dipolarophile attached to camphorsultam and a ring-opening of an enantiomerically pure vinyloxirane by lithiated dithiane served as key steps for the construction of the three stereogenic centres. Further elaborations including ring-closing metathesis and Mitsunobu inversion furnished the four diastereomeric butenolides.

Full text of DOI:10.1016/j.tetlet.2007.08.123

Tetrahedron Letters 48 (2007) 7878–7881
Synthesis of butenolides recently isolated
from marine microorganisms
Staffan Karlsson,a Fredrik Andersson,b Palle Breisteinb and Erik Hedenstro¨mb,*
aAstraZeneca R&D, SE-431 83 Mo¨lndal, Sweden
bChemistry, Department of Natural Sciences, Mid Sweden University, SE-851 70 Sundsvall, Sweden
Received 25 May 2007; revised 17 August 2007; accepted 30 August 2007
Available online 4 September 2007
Abstract—The syntheses and 13C NMR analyses of four diastereomeric butenolides, two of which were recently isolated from the
marine microorganisms Streptomycete B 5632 and Streptoverticillium luteoverticillatum 11014 are described. The two isolated buteno-
lides were found to be one of the two diastereomers (4S,10R*,11R*)-4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olide (RRS-1 or
SSS-1) and one of the two diastereomers (4S,10S*,11R*)-4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olide (SRS-1 or RSS-1). An
asymmetric 1,3-dipolar cycloaddition of a thiocarbonyl ylide with a dipolarophile attached to camphorsultam and a ring-opening
of an enantiomerically pure vinyloxirane by lithiated dithiane served as key steps for the construction of the three stereogenic cen-
tres. Further elaborations including ring-closing metathesis and Mitsunobu inversion furnished the four diastereomeric butenolides.
Ó 2007 Elsevier Ltd. All rights reserved.
O
1
Butenolides, a class of a,b-unsaturated lactones, are
13
O
substances produced by organisms such as bacteria,
12
fungi and gorgonians.1 In Streptomyces some saturated
10
4
OH
analogues function as signal substances, for example,
to cause synchronised morphological differentiation,
1
Figure 1. Two diastereomeric butenolides isolated from a marine
Streptomycete B 5632 and Streptoverticillium luteoverticillatum 11014
with S-configuration at C-4.
such as aerial mycelium and spore formation or physio-
logical differentiation leading to production of second-
ary metabolites.2 Some butenolides show inhibitor
activities3 and antifeedant properties.4
be able to determine the absolute configurations of the
two remaining stereogenic centres of the natural dia-
stereomeric butenolides.
Recently, two new butenolides were isolated from
the marine Streptomycete B 56325a and Streptoverticilli-
um luteoverticillatum 11014,5b and characterised by
13C NMR analysis as a mixture of two diastereomers
of 1 (Fig. 1). This diastereomeric mixture has shown
cytotoxic activity in human leukaemia K562 and murine
lymphoma P388 cell lines.5b The absolute configuration
at C-4 has been assigned S via CD-measurements.5a
Target molecule 1 incorporates a 3-methyl-2-alkanol
unit, which is a common structural moiety present in
several natural products.6 We have recently demon-
strated that the R*S*-isomer of this unit can be prepared
efficiently in enantiomerically pure form via an asym-
metric 1,3-dipolar cycloaddition of a thiocarbonyl ylide
with a benzyloxy substituted dipolarophile attached to
camphorsultam.7 Using such a reaction and two sequen-
tial alkylations of dithiane as key steps, we prepared the
active sex pheromone component of Macrodiprion
nemoralis.8 The final step in that sequence was simulta-
neous removal of a benzyl group and reduction of a
dithiane and a tetrahydrothiophene unit through treat-
ment with Raney-Nickel. Keeping in mind that buteno-
lides 1 incorporate a double bond and thus, should be
As no syntheses of these compounds have been reported
and since only one out of the three stereogenic centres of
butenolide 1 was determined, we decided to synthesise
all four diastereomers of 1 in enantiomerically pure
1
form, all having S-configuration at C-4. From H and
13C NMR data for these four diastereomers we should
*
Corresponding author. Tel.: +46 60 148729; fax: +46 60 148802;
e-mail: erik.hedenstrom@miun.se
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.08.123

S. Karlsson et al. / Tetrahedron Letters 48 (2007) 7878–7881
7879
O
sensitive to this reagent, we envisaged that a similar
Ref. 7 and 8
strategy, but with some modifications, could be used
for the preparation of R*S*S-isomers of 1. A Mitsunobu
reaction would then furnish the S*S*S-isomers of 1.
BnO
Xc
+
Me3Si
BnO
S
Cl
XC = (-)-Camphorsultam
In the synthesis of natural products containing a buteno-
lide unit, various methods exist for the construction of
this moiety.9 Due to its simplicity, ring-closing metathe-
sis has emerged as the most popular.10 Using such a
strategy, the diene depicted in Scheme 1 could serve as
a precursor to the R*S*S-1 isomers. To create the C-4
stereogenic centre in 1, vinyloxirane (commercially
available in both enantiomeric forms) could serve as a
building block in our synthetic sequence. Thus, two
sequential alkylations of dithiane with vinyloxirane
and a protected 3-methyl-2-alkylhalide-2-ol chiral build-
ing block (Scheme 1) followed by further transforma-
tions would result in a carbon chain containing all of
the three stereogenic centres of butenolide 1. As men-
tioned above, the enantiomerically pure 3-methyl-2-alk-
anol units were obtained via an asymmetric 1,3-dipolar
cycloaddition, followed by a two carbon chain elonga-
tion (Scheme 1).
BnO
Br
OH
d
a,b,c
S
S
SS-2
SS-3
BnO
BnO
OH
Br
e
RS-4
RS-5
Scheme 2. Synthesis of chiral building block RS-5. Reagents and
conditions: (a) (i) dimethyl malonate, NaH, THF, reflux; (ii) 0.1 M
HCl (aq); (b) NaCl, DMSO/H2O 94:6, 170 °C; (c) (i) LiAlH4, THF,
0 °C; (ii) 0.1 M HCl (aq), 71% yield from SS-2; (d) W-2 Raney-Nickel,
H2, acetone, room temperature, 5 d, 68% yield; (e) P(Ph)3, Br2,
imidazole, CH2Cl2, 91% yield.
However, all attempts failed in the ring-closing step
and only the starting material was recovered. Many
other researchers have also reported difficulties in ring-
closing when the diene substrate incorporates sulfur
atoms.11 Thus, the dithiane unit was removed before
the ring-closing-step in a three-step sequence as outlined
in Scheme 3. Dithiane RSS-7 was transformed to the
corresponding ketone using a method reported by Stork
and Zhao12 followed by condensation with p-tosyl-
hydrazide to a p-tosylhydrazone intermediate, which
was immediately reduced with catecholborane to com-
pound RSS-8 in 72% yield. We also attempted to reduce
the intermediate ketone under Huang–Minlon condi-
tions. However, only reduced retro-aldol products were
obtained.
As a representative example, we describe in detail the
total synthesis of RSS- and SSS-1, which commenced
with the construction of the chiral building block RS-5
(Scheme 2). Bromide RS-5 was obtained via a five-step
sequence from enantiomerically pure SS-2,7,8 in a good
overall yield (Scheme 2). As have been reported by us
previously for a similar compound,8 it was important
to perform the Raney-Nickel reduction (SS-3!RS-4)
in acetone, since in other solvents (alcohols, acetic acid,
toluene and THF) cleavage of the Bn–O bond also
occurred.
Bromide RS-5 was then coupled with monoalkylated
dithiane S-6, obtained from ring-opening of (R)-vinyl-
oxirane with lithiated dithiane (Scheme 3). This furni-
shed disubstituted dithiane RSS-7 in 81% yield.
Next we esterified alcohol RSS-8 by treatment with
acryloyl chloride and a base to give ester RSS-9. It
was found that when using amine bases (Et3N, DMAP
and pyridine) in various solvents, low yields of ester
RSS-9 were obtained. However, deprotonation of
RSS-8 with n-BuLi in THF followed by addition of
Our strategy was then to esterify RSS-7 with acryloyl
chloride followed by a ring-closing metathesis of the
resulting diene using either Grubbs catalyst I or II.
O
O
O
O
OP
S
OH
SRS-1 and RSS-1
OH
S
O
+
S
S
OH
+
OP
S
X
X
P = Protective group
X = Halogen
OP
OP
O
XC = Chiral auxiliary
S
+
PO
XC
Scheme 1. Retrosynthetic analysis of the diastereomeric butenolides SRS-1 and RSS-1.

7880
S. Karlsson et al. / Tetrahedron Letters 48 (2007) 7878–7881
of the a,b-unsaturated moiety.14 Although this coordi-
a
O
b
OH
+
S
S
nation to ruthenium can be circumvented by the addi-
tion of a Lewis acid such as Ti(OEt)4,14 we found it
more convenient to use catalyst II. Finally, removal of
the benzyl group of RSS-10 was accomplished by treat-
S
S
(R)-Vinyloxirane
S-6
1,3-Dithiane
15
ment with BCl3 to give RSS-1 isomer.16 SSS-1 isomer
OH
OH
e
c,d
was obtained through inversion of the configuration at
C-11 using the Mitsunobu reaction,17 followed by
hydrolysis of the intermediate ester.17 Butenolide SSS-
S
S
OBn
OBn
OBn
RSS-8
RSS-7
1
18 was obtained in poor yield, as along with the desired
O
O
product, a saturated straight chain c-keto methyl ester
(according to 1H NMR) was also isolated from the
hydrolysis. Most probably, this was formed due to iso-
merisation of the double bond and transesterification
of the butenolide with the solvent (MeOH) followed
by tautomerisation of the enol to the keto form. This
c-keto methyl ester was also isolated as a by-product
in the above described removal of the protective benzyl
group with BCl3 in compound RSS-10. Butenolides
SRS-19 and RRS-120 were prepared as above (see
Scheme 2) but using the other enantiomer of camphor-
sultam as chiral auxiliary.
O
O
g
f
OBn
PCy3
RSS-9
RSS-10
O
O
MesN
NMes
Ph
Ph
Cl
Cl
Cl
Cl
Ru
Ru
PCy3
OH
PCy3
RSS-1
SSS-1
h
I
II
Scheme 3. Reagents and conditions: (a) (i) 1,3-dithiane, n-BuLi, THF,
ꢀ20 °C, 1 h; (ii) ꢀ78 °C, (R)-vinyloxirane (0.70 equiv); (iii) NH4Cl (aq
satd), 72% yield; (b) (i) n-BuLi, THF, ꢀ20 °C, 4 h; (ii) add RS-5,
ꢀ20 °C!room temperature; (iii) NH4Cl (aq satd), 81% yield; (c)
Bis[trifluoroacetoxy]iodobenzene, MeOH/H2O 9:1, 72% yield; (d) (i) p-
toluenesulfonohydrazide, EtOH, 24 h; (ii) Catecholborane, THF, 0 °C;
(iii) NaOAcÆ3H2O, reflux, 1 h, 81% yield; (e) (i) n-BuLi, THF, 5 min;
(ii) acryloyl chloride, 84% yield; (f) Grubbs catalyst II, 5 mol %,
CH2Cl2, reflux, 1 h, 86% yield; (g) (i) BCl3 (1 M in hexane, 2 equiv),
CH2Cl2, ꢀ78 °C; (ii) MeOH at ꢀ78 °C, 48% yield; (h) (i) PPh3, 3,5-
dinitrobenzoic acid, DEAD, THF, 0 °C!room temperature; (ii)
MeOH/THF 1:1, 1 M K2CO3 (aq), 0 °C, 5% yield.
The 13C NMR data of the isolated natural butenolides
were assigned as a 1:1 diastereomeric mixture but the
assignment of the carbons made in the literature was
ambiguous.5 When comparing the published 13C NMR
data with our data for the synthetic compounds
RRS-1, SSS-1, SRS-1 and RSS-1 it was confirmed
that the resonances listed in the literature for each of
the diastereomers were a mixture of both isomers (see
Table 1). Our data show that the two naturally occur-
ring diastereomers are those with R*R*S- and S*R*S-
configuration.
acryloyl chloride resulted in a good yield of ester RSS-9.
Diene RSS-9 was then subjected to Grubbs catalyst II13
(5 mol %) to give butenolide RSS-10 in full conversion
within 1 h. It was obvious that catalyst II was superior
in comparison with catalyst I13 as low conversions were
obtained using the latter as catalyst also under pro-
longed reaction times. It is known that dienes, where
one of the double bonds is conjugated to a carbonyl,
often display low reactivity in the presence of catalyst
I, due to coordination of the catalyst to the carbonyl
In conclusion, we have accomplished the total syntheses
of enantiomerically pure diastereomeric butenolides 1,
recently isolated from marine Streptomycete B 5632 and
S. luteoverticillatum 11014, via a seven-step sequence.
According to our 13C NMR analyses the two diastereo-
mers previously isolated from natural sources by two
other research groups as a 1:1 mixture consists of
one of the two diastereomers (4S,10R*,11R*)-4,11-dihy-
droxy-10-methyl-dodec-2-en-1,4-olide (RRS-1 or SSS-1)
Table 1. 13C NMR (125 MHz, CDCl3) data for the synthetically prepared butenolides in comparison with the isolated butenolide mixture
Atom
RSS-1
SSS-1
SRS-1
RRS-1
Ref. 5aa
Ref. 5bb
1
2
3
4
5
6
7
8
9
10
11
12
13
CO
CH
CH
CH
CH2
CH2
CH2
CH2
CH2
CH
CH
CH3
CH3
173.19
121.55
156.30
83.41
33.16
24.97
29.60
26.99
32.35
39.99
71.72
19.51
14.58
173.17
121.58
156.26
83.39
33.17
24.97
29.61
27.13
32.42
39.69
71.33
20.27
14.15
173.19
121.54
156.30
83.41
33.15
24.95
29.60
26.98
32.34
39.97
71.70
19.49
14.57
173.15
121.57
156.23
83.38
33.16
24.97
29.60
27.12
32.42
39.67
71.31
20.26
14.11
173.2
121.6
156.3
83.4
32.4
25.0
29.6
27.0 (R*S*S)c
32.4
39.6 (R*R*S)c
71.3 (R*R*S)c
19.5 (R*S*S)c
14.2 (R*R*S)c
173.2
121.6
156.3
83.4
33.2
25.0
29.7
27.1 (R*R*S)c
32.4
40.0 (R*S*S)c
71.7 (R*S*S)c
20.3 (R*R*S)c
14.6 (R*S*S)c
173.2
121.5
156.3
83.4
33.1
24.9
29.6
27.0 (R*S*S)c
32.4
39.6 (R*R*S)c
71.3 (R*R*S)c
19.4 (R*S*S)c
14.2 (R*R*S)c
173.2
121.5
156.3
83.4
33.1
24.9
29.6
27.1 (R*R*S)c
32.4
39.9 (R*S*S)c
71.7 (R*S*S)c
20.2 (R*R*S)c
14.5 (R*S*S)c
a A mixture of two diastereomers in a ratio close to 1:1 (CDCl3, 75 or 125 MHz).
b A mixture of two diastereomers with unknown composition (CDCl3, 150 MHz).
c Assigned configurations based on our 13C NMR data.

S. Karlsson et al. / Tetrahedron Letters 48 (2007) 7878–7881
7881
and one of the two diastereomers (4S,10S*, 11R*)-4,11-
dihydroxy-10-methyl-dodec-2-en-1,4-olide (SRS-1 or
RSS-1).
4560; (e) Dehoux, C.; Gorrichon, L.; Baltas, M. Eur. J.
Org. Chem. 2001, 1105–1113; (f) Trost, B. M.; Muller, T.
¨
J. J. J. Am. Chem. Soc. 1994, 116, 4985–4986.
10. RCM as a key step. See for example: (a) Anand, R. V.;
Baktharaman, S.; Singh, V. K. Tetrahedron Lett. 2002, 43,
´
´
5393–5395; (b) Carda, M.; Rodrıguez, S.; Gonzalez, F.;
Acknowledgement
Castillo, E.; Villanueva, A.; Marco, J. A. Eur. J. Org.
Chem. 2002, 2649–2655; (c) Furstner, A.; Dierkes, T. Org.
Lett. 2000, 2, 2463–2465.
11. See for example: Furstner, A.; Seidel, G.; Kindler, N.
¨
¨
We are grateful for the financial support from EU
(Objective 1, the region of South Forest Countries).
Tetrahedron 1999, 55, 8215–8230; Armstrong, S. K.;
Christie, B. A. Tetrahedron Lett. 1996, 37, 9373–9376;
Shon, Y.-S.; Lee, T. R. Tetrahedron Lett. 1997, 38, 1283–
Supplementary data
1286; Mascarenas, J. L.; Rumbo, A.; Castedo, L. J. Org.
˜
Chem. 1997, 62, 8620–8621.
Experimental procedures, analytical data and NMR
spectra concerning the total synthesis of RSS-1, and
analytical data and NMR spectra for SSS-, SRS- and
RRS-1 are given. Supplementary data associated with
this article can be found, in the online version, at
doi:10.1016/j.tetlet.2007.08.123.
12. Stork, G.; Zhao, K. Tetrahedron Lett. 1989, 30, 287–290.
13. Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34,
18–29, and references cited therein.
14. See for example: (a) Ghosh, A. K.; Cappiello, J.; Shin, D.
Tetrahedron Lett. 1998, 39, 4651–4654; (b) Furstner, A.;
¨
Langemann, K. J. Am. Chem. Soc. 1997, 119, 9130–9136.
15. Williams, D. R.; Brown, D. L.; Benbow, J. W. J. Am.
Chem. Soc. 1989, 111, 1923–1925.
16. Data for RSS-1: >99% (GC). ½aꢁ2D0 +42.9 (c 0.359, MeOH),
1H NMR (500 MHz, CDCl3, Me4Si): d 0.86 (3H, d,
J = 6.7 Hz), 1.05–1.11 (m, 1H), 1.13 (3H, d, J = 6.4 Hz),
1.20–1.52 (9H, m), 1.63–1.70 (1H, m), 1.74–1.81 (1H, m),
3.65 (1H, quintet, J ꢂ 6.1 Hz), 5.03–5.06 (1H, m), 6.11
(1H, dd, J = 5.7, 2.0 Hz), 7.46 (1H, dd, J = 5.7, 1.4 Hz).
13C NMR (125 MHz, CDCl3, Me4Si): see Table 1. MS
(EI) m/z (relative intensity): 227 (MH+, 20%), 209
(MH+ꢀH2O, 53), 191 (9), 182 (5), 164 (8), 149 (9), 135
(8), 122 (100), 107 (18), 97 (60), 81 (21), 67 (23), 55 (40), 45
(29). LC–HRMS: Found (M+ꢀH, C13H21O3) 225.1490,
calcd (M+ꢀH, C13H21O3) 225.1496.
References and notes
1. See for example: (a) Smith, C. J.; Abbanat, D.; Bernan, V.
S.; Maiese, W. M.; Greenstein, M.; Jompa, J.; Tahir, A.;
Ireland, C. M. J. Nat. Prod. 2000, 63, 142–145; (b) Guo,
Y.-W.; Gavagnin, M.; Mollo, E.; Trivellone, E.; Cimino,
´
G. J. Nat. Prod. 1999, 62, 1194–1196; (c) Rodrıguez, A. B.;
Ramırez, C. J. Nat. Prod. 1994, 57, 339–347; (d) Braun,
´
´
D.; Pauli, N.; Sequin, U.; Zha¨ner, H. FEMS Microbiol.
Lett. 1995, 126, 37–42.
2. (a) Yamada, Y.; Nihira, T. In Comprehensive Natural
Product Chemistry; Barton, D., Nakanishi, K., Eds.;
Elsevier: Oxford, 1999; Vol. 8, pp 377–413; (b) Sakuda,
S.; Tanaka, S.; Mizuno, K.; Sukcharoen, O.; Nihira, T.;
Yamada, Y. J. Chem. Soc., Perkin Trans. 1 1993, 2309–
2315.
3. Ishigami, K.; Kitahara, T. Tetrahedron 1995, 51, 6431–
6442.
4. Pawlick, J. R.; Fenical, W. Mar. Ecol. Prog. Ser. 1992, 87,
183–188.
´
17. Razikin, J.; Gonzalez, A.; Gil, P. Tetrahedron: Asymmetry
1996, 7, 3479–3484.
18. Data for SSS-1: 87% (GC). H NMR (500 MHz, CDCl3,
1
Me4Si): d 0.88 (3H, d, J = 6.7 Hz), 1.09–1.16 (1H, m), 1.15
(3H, d, J = 6.3 Hz), 1.24–1.53 (9H, m), 1.64–1.71 (1H, m),
1.74–1.79 (1H, m), 3.69–3.73 (1H, m), 5.03–5.06 (1H, m),
6.11 (1H, dd, J = 5.7, 1.9 Hz), 7.45 (1H, dd, J = 5.7,
1.3 Hz). 13C NMR (125 MHz, CDCl3, Me4Si): see Table 1.
MS (EI) m/z (relative intensity): 227 (MH+, 4%), 209
(MH+ꢀH2O, 33), 191 (6), 182 (7), 164 (8), 149 (7), 135 (9),
122 (100), 107 (17), 97 (83), 81 (27), 67 (30), 55 (48), 45
(32). LC–HRMS: Found (M+ꢀH, C13H21O3) 225.1502,
calcd (M+ꢀH, C13H21O3) 225.1496.
5. (a) Mukku, V. J. R. V.; Speitling, M.; Laatsch, H.;
Helmke, E. J. Nat. Prod. 2000, 63, 1570–1572; (b) Li,
D.-H.; Zhu, T.-J.; Liu, H.-B.; Fang, Y.-C.; Gu, Q.-Q.;
Zhu, W.-M. Arch. Pharm. Res. 2006, 29, 624–626.
6. See for example: (a) Nakamura, Y.; Mori, K. Eur. J. Org.
Chem. 1999, 2175–2182; (b) Larsson, M.; Nguyen, B.-V.;
Ho¨gberg, H.-E.; Hedenstro¨m, E. Eur. J. Org. Chem. 2001,
353–363; (c) Tai, A.; Higashiura, Y.; Kakizaki, M.; Naito,
T.; Tanaka, K.; Fujita, M.; Sugimura, T.; Hara, H.;
Hayashi, N. Biosci. Biotechnol. Biochem. 1998, 62, 607–
608; (d) De Marino, S.; Iorizzi, M.; Palagiano, E.; Zollo,
F.; Roussakis, C. J. Nat. Prod. 1998, 61, 1319–1327; (e)
Middleton, R. F.; Foster, G.; Cannel, R. J. P.; Sidebot-
tom, P. J.; Taylor, N. L.; Noble, D.; Todd, M.; Dawson,
M. J.; Lawrence, G. C. J. Antibiot. 1995, 48, 311–316.
7. Karlsson, S.; Ho¨gberg, H.-E. Org. Lett. 1999, 1, 1667–
1669.
8. Karlsson, S.; Ho¨gberg, H.-E. Synthesis 2000, 1863–1867.
9. See for example: (a) Hanessian, S.; Roy, P. J.; Petrini, M.;
Hodges, P. J.; Di Fabio, R.; Carganico, G. J. Org. Chem.
1990, 55, 5766–5777; (b) de March, P.; Figueredo, M.;
Font, J.; Raya, J.; Alvarez-Larena, A.; Piniella, J. F. J.
Org. Chem. 2003, 68, 2437–2447; (c) Konno, H.; Makabe,
H.; Tanaka, A.; Oritani, T. Tetrahedron Lett. 1996, 37,
5393–5396; (d) Zask, A. J. Org. Chem. 1992, 57, 4558–
19. Data for SRS-1: >99% (GC). ½aꢁ2D0 +70.9 (c 0.115, MeOH),
1H NMR (500 MHz, CDCl3, Me4Si): d 0.87 (3H, d,
J = 6.7 Hz), 1.06–1.16 (1H, m), 1.13 (3H, d, J = 6.3 Hz),
1.21–1.53 (9H, m), 1.63–1.70 (1H, m), 1.74–1.81 (1H, m),
3.65 (1H, quintet, J ꢂ 6.1 Hz), 5.03–5.06 (1H, m), 6.11
(1H, dd, J = 5.7, 2.0 Hz), 7.46 (1H, dd, J = 5.7, 1.4 Hz).
13C NMR (125 MHz, CDCl3, Me4Si): see Table 1. MS
(EI) m/z (relative intensity): 227 (MH+, 34%), 209
(MH+ꢀH2O, 76), 191 (13), 182 (6), 163 (11), 149 (11),
135 (11), 122 (100), 111 (21), 97 (48), 81 (22), 67 (22), 55
(41), 45 (29). LC–HRMS: Found (M+ꢀH, C13H21O3)
225.1510, calcd (M+ꢀH, C13H21O3) 225.1496.
20. Data for RRS-1: 90% (GC). 1H NMR data not given
because of interfering impurities for complete interpreta-
tion. 13C NMR (125 MHz, CDCl3, Me4Si): see Table 1.
MS (EI) m/z (relative intensity): 227 (MH+, 35%), 209
(MH+ꢀH2O, 81), 191 (14), 182 (5), 164 (10), 147 (9), 135
(10), 122 (100), 107 (20), 97 (52), 83 (19), 67 (23), 55 (42),
45 (30). LC–HRMS: Found (M+ꢀH, C13H21O3) 225.1503,
calcd (M+ꢀH, C13H21O3) 225.1496.