Synthesis of a C(4)-C(9) eleutheside template from D-glucal

Article abstract of DOI:10.1016/S0040-4020(00)01117-0

D-Glucal is converted to epoxy allylic alcohol 4 using an eight-step sequence that features a stereoselective methyl Grignard addition to an iodo-hexenulose. Epoxide formation via intramolecular iodide displacement occurs subsequent to an unusual hemiacetal reduction protocol involving LiBH₄ in n-octanol. Alcohol 4 and the corresponding aldehyde (Z)-14 are potential C(4)-C(9) templates for eleutheside syntheses.

Full text of DOI:10.1016/S0040-4020(00)01117-0

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1183±1187
Synthesis of a C(4)±C(9) eleutheside template from d-glucalq
Kolbot By, Patrick A. Kelly, Mark J. Kurth, Marilyn M. Olmstead and Michael H. Nantzp
Department of Chemistry, University of California, Davis, CA 95616, USA
Received 19 October 2000; accepted 29 November 2000
AbstractÐd-Glucal is converted to epoxy allylic alcohol 4 using an eight-step sequence that features a stereoselective methyl Grignard
addition to an iodo-hexenulose. Epoxide formation via intramolecular iodide displacement occurs subsequent to an unusual hemiacetal
reduction protocol involving LiBH4 in n-octanol. Alcohol 4 and the corresponding aldehyde (Z)-14 are potential C(4)±C(9) templates for
eleutheside syntheses. q 2001 Elsevier Science Ltd. All rights reserved.
Eleutherobin (1, Scheme 1), ®rst reported by Fenical and
co-workers,1 is a potent cytotoxic marine natural product
that mimics the action of paclitaxel (taxol2) by binding to
tubulin and effectively stabilizing microtubules.3 This
action leads to mitotic arrest and is the subject of con-
siderable recent interest given that paclitaxel, eleutherobin,
and other notable microtubule-stabilizing natural products
such as epothilones A and B4 and discodermolide5 appear to
operate by binding to a common site on the microtubule
polymer.6,7 Total syntheses of eleutherobin, and the closely
related sarcodictyins A and B (2, 3),8 have been reported by
Nicolaou et al.9 and Danishefsky and co-workers.10 To date,
the correlation of activity for tubulin polymerization
with structure has been examined for eleutherobin and
sarcodictyin derivatives wherein structural alterations resided
either within the core 10-membered ring or the accompanying
side chains.11,12 The relative scarcity of these marine natural
products has hampered further biological evaluations.13
We14 and other investigators recently presented new
approaches to eleutherobin and eleutheside analogs.15±18
Our current aim is to synthesize the eleutheside core
Scheme 1. d-Glucal as a progenitor of eleutheside C(4)±C(9).
q A preliminary account of this work was presented at the 219th National Meeting of the American Chemical Society, San Francisco, CA; see: By, K.; Kelly,
P. A.; Kurth, M. J.; Nantz, M. H. ACS Books of Abstracts, 26±30 March 2000, ORGN-851.
Keywords: eleutheside; epoxide; stereoselective; d-glucal; hexenulose.
Corresponding author. Tel.: 11-530-752-6357; fax: 11-530-752-8995; e-mail: mhnantz@ucdavis.edu
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01117-0

1184
K. By et al. / Tetrahedron 57 (2001) 1183±1187
Table 1. Base-catalyzed reaction of 13!14115
Entry Reaction conditionsa
Aldehyde 14
Anhydro 15
Yield, %b (Z:E)c Yield, %b
1
2
3
4
5
6
7
8
9
NaH, THF, 08C, 1 h
KH, THF, 08C, 2 h
KOt-Bu, CH2Cl2, 08C±rt, 16 h 49 (10:1)
0
0
65
75
44
77
50
60
22
35
75
KOt-Bu, THF, 08C±rt, 8 h
DBU, CH2Cl2, 08C±rt, 14 h
NaOCH3, CH3OH, 08C±rt, 8 h
K2CO3, acetone, rt, 16 h
0
11 (0:100)
0
34 (100:0)
26 (10:1)
LiCH2S(O)CH3, DMSO, rt, 2 h 3 (0:100)
Cs2CO3, acetone, rt, 16 h
Scheme 2. (a) BF3´Et2O, MeOH, C6H6, rt, 45 min; (b) KCN, MeOH, rt, 4 h,
95% (2 steps); (c) MnO2, CH2Cl2, rt, 2 h, 55%; (d) [(PhO)3PCH3]I, DMF, rt,
2 h, 72%.
a
For each entry, 13 (0.2±0.3 mmol) was treated with excess base (ca.
4 equiv.).
Isolated.
Determined by 1H NMR integration.25
b
c
structure via intramolecular Diels±Alder reaction of a
dienophile tethered to C(8).14b This strategy requires an
enantioenriched C(4)±C(9) template. In this regard, we
present herein a stereoselective synthesis of epoxy allylic
alcohol 4 (Scheme 1), whose origin is traced through
pyranoside 5 to commercially available tri-O-acetyl-d-
glucal (6).
At this stage, our strategy was to facilitate the hemiacetal
equilibrium to an open form d-oxido aldehyde wherein
intramolecular iodide displacement would yield the corre-
sponding C(8)-epoxide.28 To our dismay, we found that
treatment of 13 with a variety of bases provided a mixture
of products principally consisting of (E)- and (Z)-epoxy
aldehydes 1429 and the anhydro-1,6-pyranoside 15
(Table 1). Although formation of desired (Z)-14 was
in¯uenced by selection of base and solvent, we were unable
to thwart the formation of 15 as a major product. Addition-
ally, alkene isomerization appeared to be problematic in the
presence of excess homogeneous base. The use of K2CO3 in
acetone (entry 7) afforded the best ratio of (Z)-14 but in low
yield. Consequently, we sought to obtain aldehyde 14 by
reduction of the hemiacetal moiety to circumvent anhydro-
pyranoside formation.
Using a combination of literature procedures, tri-O-acetal-
d-glucal 6 was readily converted in four steps to hexenulose
10 (Scheme 2).19 Exposure of 6 to boron tri¯uoride etherate
and methanol in benzene afforded methyl 4,6-di-O-acetyl-
2,3-dideoxy-2-enopyranoside (7).20 The acetate esters were
cleaved using potassium cyanide in methanol to obtain diol
821 as an 8:1 mixture of a:b anomers and subsequent treat-
ment with excess manganese dioxide afforded hex-2-en-4-
ulose 9 as a single diastereomer.22 Comparison of the
speci®c activity with that of the literature revealed that
these transformations occurred without loss of optical
25
activity (compound 9: ‰aŠ ˆ 133:28 (cˆ0.78, CHCl3),
D
23
23
D
literature ‰aŠ ˆ 136:18 (cˆ2.66, CHCl3). An alcohol-
to-iodide conversion was then conducted using methyl-
triphenoxyphosphonium iodide according to Landauer and
Rydon to give iodo-hexenulose 10.24
We envisioned introduction of the eleutheside C(7) methyl
by stereoselective nucleophilic addition to the b-face of
hexenulose 10. Indeed, prior work by Achmatowicz et al.
has shown that treatment of a trityl-protected hexenulose
analogous to 9 with MeLi or BuLi gave the corresponding
erythro products as the major isomers.25 We found that
treatment of 10 with MeMgBr in Et2O gave a 14:1 mixture
of methyl adducts (Scheme 3).26 Single crystal X-ray analy-
sis con®rmed the major product to be a-hydroxy adduct
11.27 Subsequent benzylation gave 12 and set the stage for
acetal hydrolysis. The methyl glycoside linkage of 12 was
unexpectedly resistant to hydrolysis and required heating in
aqueous acetic acid to deliver hemiacetal 13 as a 5:1 mixture
of anomers.
Table 2. Formation of epoxy alcohol 4
Entry
Reaction conditionsa
% Yield (4)
1
2
3
4
5
6
NaBH4, MeOH, 08C±rt
LiAlH4, THF, 278 to 2308C
(nBu)4NBH4, THF, 08C±rt
Dibal-H,b pentane, 08C±rt
LiBH4, Et2O, 08C
34
33
20
,10
44
47
LiBH4, 10:1 Et2O:CH3OH,
08C±rt
7
8
LiBH4, CH3OH, 08C±rt
LiBH4, CH3(CH2)6CH2OH,
08C±rt
57
88
a
For all entries except 4, 13 at a concentration of 0.1±0.2 M was treated
with excess hydride (ca. 8 equiv.); all crude reaction mixtures were subse-
quently treated with KOH (s) in CH2Cl2 at 08C and followed by chromato-
graphy to isolate 4.
Scheme 3. (a) MeMgBr, Et2O, 08C±rt, 6 h, 80%; (b) NaH, BnBr, TBAI,
THF, 08C±rt, 10 h, 77%; (c) 1.7:3:1, 1,4-dioxane:H2O:AcOH, re¯ux, 4.5 h,
84%.
b
2.0 equiv.

K. By et al. / Tetrahedron 57 (2001) 1183±1187
1185
Hydride reduction of 13 gave a mixture of products that
included the expected C(4),C(8)-diol (not depicted). Base
treatment of the crude reaction mixture after work-up (KOH
(s), CH2Cl2, 08C) gave rise to epoxide 4 in varying yields
(Table 2). The reduction was sensitive to temperature in that
warming above room temperature led to the formation of 15.
Ole®n isomerization was not observed under any of the
conditions. The use of ether or THF for this reaction resulted
in signi®cant product mixtures containing unreacted starting
material, a problem that was somewhat ameliorated by a
change in solvent to methanol. The use of LiBH4 in metha-
nol (entry 7) was slightly more effective than NaBH4 in
methanol (entry 1). We were grati®ed to ®nd that substitu-
tion of methanol with n-octanol (entry 8) further enhanced
the formation of 4. The underlying basis for this improve-
ment in yield is unclear and is the subject of current studies.
MnO2 oxidation of 4 conveniently afforded aldehyde (Z)-14
in 82% yield. Although MnO2 oxidation of (Z)-4-(benzyl-
oxy)-but-2-en-1-ol has been shown to afford mixtures of E
and Z isomers,30 no (E)-isomer was detected in the oxidation
of 4 presumably due to the non-enolizable nature of 14.
74.1, 94.1, 127.8, 143.8, 195.7. Anal. calcd for C7H10O4: C,
53.16; H, 6.37. Found: C, 53.12; H, 6.29.
1.1.2. Methyl 6-deoxy-6-iodo-2,3-dideoxy-a-d-glycero-4-
pyranosidulose (10). To a solution of 9 (2.0 g, 12.8 mmol)
in dry DMF (100 ml) at room temperature was added
methyltriphenoxyphosphonium iodide (11.6 g, 25.6 mmol)
in one portion. After stirring 1 h, methanol (8 ml) was added
to the dark red reaction mixture and the reaction was stirred
an additional 45 min before diluting with Et2O (200 ml) and
quenching by addition of aq. 15% Na2S2O3. The layers were
separated and the aqueous layer was extracted with Et2O
(£2). The combined organic extract was washed with
brine and dried (MgSO4). After solvent removal using rotary
evaporation, ¯ash chromatography of the residue (8:1
hexane:EtOAc) gave impure 10 (5.8 g). This material was
further puri®ed by trituration with Et2O (5 ml). Filtration of
the crystals and subsequent washing with hexane gave 10
(2.2 g) as colorless crystals. The mother liquor was concen-
trated and the above procedure was repeated to obtain an
additional quantity of 10 (0.26 g, 72% overall); mp 89.6±
25
91.58C; TLC, Rfˆ0.75 (EtOAc); ‰aŠ ˆ 59:88 (cˆ1.45,
D
In summary, an eight-step synthesis of a C(4)±C(9)
template for eleutheside synthesis has been achieved from
d-glucal in 17% overall yield. We are currently examining
the elaboration of 4 via epoxide cleavage reactions at C(9)
and are using aldehyde 14 for chain extensions at C(4).
CHCl3); IR 3029, 2830, 1698, 1629 cm21
;
1H NMR d
3.46 (dd, Jˆ6.9, 10.8 Hz, 1H), 3.59 (s, 3H), 3.61 (dd,
Jˆ3.0, 10.8 Hz, 1H), 4.51 (dd, Jˆ3.0, 6.9 Hz, 1H), 5.18
(d, Jˆ3.6 Hz, 1H), 6.10 (d, Jˆ10.2 Hz, 1H), 6.90 (dd,
Jˆ3.6, 10.2 Hz, 1H); 13C NMR d 1.9, 56.8, 73.6, 94.5,
127.2, 144.0, 193.4. Anal. calcd for C7H9O3I: C, 31.36, H,
3.38. Found: C, 30.97; H, 3.21.
1. Experimental section
1.1. General
1.1.3. Methyl 6-deoxy-6-iodo-4-methyl-2,3-dideoxy-a-d-
erythro-pyranoside (11). To a solution of 10 (2.42 g,
9.03 mmol) in Et2O (180 ml) at 08C was added MeMgBr
(3.6 ml of 3.0 M solution in Et2O, 10.8 mmol) dropwise.
After 30 min, the reaction mixture was warmed to room
temperature and stirred 6.5 h before diluting with Et2O
and quenching by addition of water. The layers were sepa-
rated and the aqueous layer was extracted with Et2O (£2).
The combined organic extract was washed with brine and
dried (MgSO4). After solvent removal via rotary evapora-
tion, the residue was chromatographed (5:1 hexane:EtOAc)
to obtain 11 (2.05 g, 80%) as a white solid, mpˆ86±878C;
CH2Cl2); IR 3434, 2967, 2830, 1679 cm21; 1H NMR d 1.13
(s, 3H), 2.06 (s, 1H, ZOH), 3.15 (t, Jˆ10.8, 1H), 3.56 (m,
1H), 3.60 (s, 3H), 4.00 (dd, Jˆ1.8, 11.1, 1H), 4.89 (d,
Jˆ3.0 Hz, 1H), 5.65 (dd, Jˆ2.7, 9.9 Hz, 1H), 5.80 (d,
Jˆ10.8 Hz, 1H); 13C NMR d 3.0, 19.5, 56.5, 69.9, 76.4,
95.9, 125.0, 137.7. A sample of 11 was recrystallized
from Et2O:hexane to obtain needles suitable for X-ray
crystallographic analysis (see Supporting information).
All reactions were carried out under an atmosphere of
nitrogen. CH2Cl2 was distilled from calcium hydride
immediately prior to use. THF and Et2O were distilled
from sodium benzophenone ketyl immediately prior to
use, and benzene was distilled from sodium. Column chro-
matography was carried out using 230±400 mesh silica gel,
slurry packed in glass columns, eluting with the solvents
indicated. TLC was performed on Kieselgel 60 F254 plates,
staining with an ethanolic solution of p-anisaldehyde
25
D
1
containing 5% conc. H2SO4. H NMR (300 MHz) and 13C
TLC, Rfˆ0.39 (1:1 hexane:EtOAc); ‰aŠ ˆ 1348 (cˆ10.1,
NMR (75 MHz) were recorded in CDCl3. High resolution
mass spectrometry was performed by Mass Spectrometry
Service Labs of the University of California, Davis, the
University of Minnesota (Minneapolis) and the University
of California, Riverside. Infrared (IR) data were obtained on
neat samples. Elemental analyses were performed by
Midwest Microlab, LLC (Indianapolis).
1.1.1. Methyl 2,3-dideoxy-a-d-glycero-4-pyranosidulose
(9). To a solution of diol 8 (6.5 g, 41 mmol) in CH2Cl2
(2.70 l) was added MnO2 (70 g, 0.59 mol). The suspension
was stirred 2 h at room temperature and then ®ltered through
a pad of celite. After removal of the solvent by rotary
evaporation, the residue was chromatographed (9:1 EtOA-
1.1.4. Methyl 6-deoxy-6-iodo-4-O-benzyl-4-methyl-2,3-
dideoxy-a-d-erythro-glucopyranoside (12). To a suspen-
sion of sodium hydride (0.48 g, 9.1 mmol) in THF (95 ml) at
08C was added a solution of 11 (1.85 g, 6.5 mmol) in THF
(25 ml) via cannula. The reaction was allowed to warm to
room temperature and then recooled to 08C after 45 min
whereupon benzyl bromide (0.93 ml, 7.8 mmol) and tetra-
butylammonium iodide (0.53 g, 1.3 mmol) were added
successively. The reaction was stirred at room temperature
for 10 h and then diluted with Et2O and quenched by
addition of water. The layers were separated and the
c:hexane) to afford 9 (3.33 g, 55%) as a white solid, mp 84±
868C (lit.22 mp 82.58C); TLC, Rfˆ0.58 (EtOAc); ‰aŠ
ˆ
25
D
33:28 (cˆ0.78, CHCl3); IR 3257, 1697 cm21; H NMR d
2.35 (br. s, 1H, ZOH), 3.55 (s, 3H), 4.01 (m, 2H), 4.85 (t,
Jˆ4.5 Hz, 1H), 5.18 (d, Jˆ3.6 Hz, 1H), 6.11 (d, Jˆ10.2 Hz,
1H), 6.92 (dd, Jˆ3.6, 10.2 Hz, 1H); 13C NMR d 56.7, 61.6,
1

1186
K. By et al. / Tetrahedron 57 (2001) 1183±1187
aqueous layer was extracted with Et2O (£2). The combined
organic extract was washed with brine and dried (MgSO4).
After removal of the solvents via rotary evaporation, chro-
matography (5:1 hexane:EtOAc) gave 12 (1.92 g, 77%) as a
light yellow oil; TLC, Rfˆ0.66 (4:1 hexane:EtOAc);
Jˆ3.0 Hz, 1H), 5.65 (dd, Jˆ1.4, 9.6 Hz, 1H), 6.14 (dd,
Jˆ3.2, 9.5 Hz, 1H), 7.33 (m, 5H); 13C NMR d 22.6, 63.3,
67.1, 73.2, 80.3, 95.2, 127.2, 127.3, 128.2, 129.5, 131.0,
139.7. Anal. calcd for C14H16O3: C, 72.39; H, 6.94.
Found: C, 71.91; H, 7.00.
23
[a]D ˆ58.28 (cˆ2.42, CHCl3); IR 2927, 1698,
1635 cm21; H NMR d 1.21 (s, 3H), 3.16 (t, Jˆ10.8 Hz,
1
1.1.8. 4-[(2R)-Oxiran-2-yl)-(4S)-(2Z)-4-(phenylmethoxy)]-
pent-2-en-1-ol (4). To a solution of 13 (2.99 g, 8.30 mmol)
in n-octanol (50 ml) at 08C was added lithium borohydride
(0.40 g, 18.3 mmol) portion wise over 5 min. After stirring
24 h at room temperature, the reaction was quenched by
slow addition of water and the resultant mixture was
extracted with Et2O (3£300 ml). The combined organic
extract was washed with brine and dried (Na2SO4). The
Et2O was removed by rotary evaporation and the remaining
solution was loaded onto a SiO2 column (ca. 300 g) and
eluted with 9:1 hexane:EtOAc to remove the n-octanol
(TLC). Subsequent elution with EtOAc followed by concen-
tration of the collected fractions afforded a crude mixture of
4 and its diol progenitor. The crude mixture was dissolved in
CH2Cl2 (100 ml) and cooled to 08C. To this mixture was
added KOH (s) (ca. 0.5 g) in one portion. After stirring 4 h
at 08C, the reaction mixture was ®ltered through a pad of
celite and the ®ltrate was concentrated by rotary evapora-
tion. Chromatography (4:1 hexane:EtOAc) of the residue
gave 4 (1.72 g, 88%) as an oil; TLC, Rfˆ0.3 (2:1 hexane:
1H), 3.52 (dd, Jˆ1.5, 10.8 Hz, 1H), 3.62 (s, 3H), 4.37 (dd,
Jˆ1.5, 11.1 Hz, 1H), 4.50 (dd, Jˆ11.7, 14.4 Hz, 2H), 4.90
(d, Jˆ2.7 Hz, 1H), 5.80 (dd, Jˆ2.7, 10.2 Hz, 1H), 5.95 (d,
Jˆ10.2 Hz, 1H), 7.30 (m, 5H); 13C NMR d 3.6, 19.2, 56.5,
65.6, 72.2, 75.3, 95.9, 127.1, 127.2, 127.5, 128.4, 135.4,
138.6; HRMS m/z calcd for [M1Na]1 397.02785, found
397.0276.
1.1.5. 6-Deoxy-6-iodo-4-O-benzyl-4-methyl-2,3-dideoxy-
a-d-erythro-glucopyranose (13). To a solution of 12
(0.50 g, 1.34 mmol) in a solvent mixture of 1,4-dioxane
(5 ml) and water (9 ml) at room temperature was added
acetic acid (3 ml). The reaction was heated to re¯ux for
4.5 h and then allowed to cool to room temperature before
quenching by slow addition of saturated aq. NaHCO3 to a
pH 5±6. The reaction mixture was extracted with Et2O and
the combined organic extract was washed with brine and
dried (Na2SO4). After solvent removal via rotary evapora-
tion, the residue was chromatographed (5:1 hexane:EtOAc)
to obtain 13 (0.41 g, 84%) as a light yellow oil; TLC,
25
EtOAc); ‰aŠ ˆ15:38 (cˆ3.83, CHCl3); IR 3417, 1454,
D
1
1027 cm21; H NMR d 1.44 (s, 3H), 2.51 (s, 1H, ZOH),
23
Rfˆ0.49 (1:1 hexane:EtOAc); ‰aŠ ˆ7:098 (cˆ1.60,
D
1
CHCl3); IR 3414, 3030, 2869, 1692, 1653 cm21; H NMR
2.60 (dd, Jˆ2.7, 4.5 Hz, 1H), 2.75 (apparent t, Jˆ4.5 Hz,
1H), 3.16 (dd, Jˆ2.7, 4.2 Hz, 1H), 4.18 (m, 1H), 4.39 (m,
1H), 4.50 (s, 2H), 5.20 (d, Jˆ12 Hz, 1H), 5.87 (dt, Jˆ6.3,
12.0 Hz, 1H), 7.32 (m, 5H); 13C NMR d 22.9, 43.3, 56.9,
59.1, 65.4, 76.6, 127.3, 127.4, 127.8, 128.3, 135.3, 138.5;
HRMS m/z calcd for [M1Na]1 257.1148, found 257.1150.
d 1.21 (s, 3H), 3.10 (t, Jˆ10.8 Hz, 1H), 3.55 (dd, Jˆ1.8,
10.8 Hz, 1H), 4.50 (m, 1H), 4.52 (d, Jˆ3, 2H), 5.46 (d,
Jˆ2.4 Hz, 1H), 5.90 (dd, Jˆ2.7, 10.2 Hz, 1H), 5.97 (d,
Jˆ10.5 Hz, 1H), 7.32 (m, 5H); 13C NMR d 3.9, 19.0,
65.6, 72.3, 75.2, 89.3, 127.2, 127.6, 127.8, 128.5, 135.3,
138.6. Anal. calcd for C14H17: C, 46.68; H, 4.76. Found:
C, 46.78; H, 4.76.
1.1.9. Supporting information available. 13C NMR spectra
for compounds 4, 12 and (Z)-14 and the 1H NMR spectrum
of 4, X-ray crystallographic data for 11 (12 pages). This
material is available free of charge via the Internet at
http://pubs. acs.org.
1.1.6. 4-[(2R)-Oxiran-2-yl)-(4S)-(2Z)-4-(phenylmethoxy)]-
pent-2-enal (Z-14). To a solution of 13 (155 mg,
0.43 mmol) in dry acetone (30 ml) was added anhydrous
potassium carbonate (640 mg, 4.64 mmol). The suspension
was stirred at room temperature for 17 h and then diluted
with ether (30 ml). The reaction mixture was ®ltered
through a pad of celite and the ®ltrate was concentrated
by rotary evaporation. The residue was chromatographed
(4:1 hexane:EtOAc) to obtain 14 (34 mg, 34%) and 15
(22 mg, 22%) as oils. (Z)-14: TLC, Rfˆ0.27 (7:3 hexane:
Acknowledgements
We thank the UC Cancer Research Coordinating Committee
for partial support of this work. Thanks are due to Dr
Brendan Twamley for assistance with X-ray crystallo-
graphy.
23
EtOAc); ‰aŠ ˆ237:58 (cˆ0.79, CHCl3); IR 3033, 1716
D
1
(CyO), 1277 cm21; H NMR d 1.58 (s, 3H), 2.62 (dd,
Jˆ2.7, 4.5 Hz, 1H), 2.83 (t, Jˆ4.2 Hz, 1H), 3.26 (dd,
Jˆ3.2, 3.9 Hz, 1H), 4.58 (s, 2H), 6.05 (dd, Jˆ7.8, 12 Hz,
1H), 6.22 (d, Jˆ12 Hz, 1H), 7.31 (m, 5H), 10.39 (d,
Jˆ7.8 Hz, 1H); 13C NMR d 22.7, 42.9, 55.9, 65.7, 78.5,
127.5, 128.5, 133.2, 137.8, 145.6, 155.7, 193.7; HRMS
m/z calcd for [M1Na]1 255.0997, found 255.1003. Anal.
calcd for C14H16O3´0.5H2O: C, 69.69; H, 7.10. Found: C,
69.35; H, 6.74.
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EtOAc); IR 3031, 2973, 1633, 985 cm21; H NMR d 1.31
(s, 3H), 3.70 (d, Jˆ7.8 Hz, 1H), 3.88 (t, Jˆ7.8 Hz, 1H), 4.58
(dd, Jˆ5.4, 11.7 Hz, 2H), 4.80 (d, Jˆ11.7 Hz, 1H), 5.57 (d,

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1
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