Enantioselective synthesis of 11-substituted 2- or 3-methoxy-17-vinylgona-1,3,5(10)-trien-13-ols

Article abstract of DOI:10.1016/j.tet.2008.10.073

The acylation of the (±)-spiro-γ-lactone 1 lithium enolate (3 equiv) by the O-TBDMS methyl (-)-(S)-lactate, the O-TBDMS methyl (+)-(S)-mandelate, or the diacetone-d-glucose carbonate (1 equiv each) occurs with a kinetic resolution. The (S,S)-enolate is th

Full text of DOI:10.1016/j.tet.2008.10.073

Tetrahedron 65 (2009) 177–193
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Enantioselective synthesis of 11-substituted 2- or 3-methoxy-17-vinylgona-
1,3,5(10)-trien-13-ols
,
Delphine Moraleda a, Michel Giorgi b, Maurice Santelli a
*
a Faculte´ des Sciences de St-Je´roˆme, Universite´ d’Aix-Marseille, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
b SpectropoˆledCentre Scientifique St-Je´roˆme, Universite´ d’Aix-Marseille, Facult´e de St-Je´roˆme, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The acylation of the (ꢀ)-spiro-
g
-lactone 1 lithium enolate (3 equiv) by the O-TBDMS methyl (ꢁ)-(S)-
-glucose carbonate (1 equiv each)
Received 8 September 2008
Accepted 23 October 2008
Available online 26 October 2008
lactate, the O-TBDMS methyl (þ)-(S)-mandelate, or the diacetone-
D
occurs with a kinetic resolution. The (S,S)-enolate is the most reactive with the lactate and it is the (R,R)-
enolate, which selectively reacts with the mandelate or the DAG carbonate. After alkylation of the re-
sulting acyl lactones with 4- or 5-methoxy-1-iodobenzocyclobutene and heating, title compounds were
obtained and, after deprotection, the structures of the optically pure new steroids were ascertained by
single crystal X-ray analysis.
Keywords:
Acylation
Kinetic resolution
Diastereoselectivity
Steroids
Ó 2008 Elsevier Ltd. All rights reserved.
Chiral pool
1. Introduction
three optically active unnatural steroids (bearing a 11-bornyloxy-
carbonyl group) have been obtained, but the purification of these
Recent trends in pharmaceutical chemistry have triggered
a move away from the development of racemates to the de-
velopment of single enantiomer drugs.1 In this context, the enan-
tioselective synthesis of steroids is of considerable importance in
medical chemistry.2 The enantioselective total synthesis of steroids
has been improved by the preparation of the indenedione of Hajos–
Parrish–Eder–Sauer–Wiechert and by its use for the preparation of
various steroids.3 Other specific strategies are less straightforward
and often involve molecules from the chiral pool.2
The importance of steroids is underlined by the fact that it is
estimated that fully one-third of drugs available for prescription
either are or contain steroids.4 Some non-natural steroids possess
enhanced activity5 and, particularly, 19-norsteroids are often more
biologically active than the methylated counterpart.6 As example of
steroids that do not exist in Nature, RU-486 is a strong progesterone
and glucocorticoid antagonist.7
steroids was very laborious (Scheme 1).10 In order to introduce the
pharmacophore lactoyl group in the 11-position of steroids, we
have also used the protected methyl (ꢁ)-(S)-lactate as acylating
reagent, but some problems appeared and the synthesis has been
unsuccessful. These facts have led us to modify the acylation re-
action conditions as well as the following steps and now we present
our progress in this area.
2. Results and discussion
2.1. Kinetic resolution from methyl O-TBDMS-(L)-(S)-lactate
The addition of methyl (ꢁ)-(S)-lactate protected by the tert-
butyldimethylsilyl group to 3 equiv of racemic spirolactone 1 lith-
ium enolate gives rise to a mixture of a-ketospirolactone 2 after
20 h at ꢁ60 ꢂC (Scheme 2). Unfortunately, the existence of tauto-
meric equilibrium for each diastereomer (R,R)-2 and (S,S)-2 did not
allow their separation. Alkylation of 2 by 4- or 5-methoxy-1-
iodobenzocyclobutene afforded steroid precursor 3a or 3b. As
demonstrated in previous works, alkylation occurred with a high
stereoselectivity: the attack took place at the face of the enolate
bearing the vinyl group anti to the lactone ring–oxygen linkage.11
Minor by-product 4a or 4b (mixture of isomers) coming from the
loss of the protected group was obtained as in the previous work.10
Precursor 3a or 3b was thermolyzed in trichlorobenzene at
Some years ago, we have reported a convergent 19-norsteroids
synthesis based on the AþD/AD/ABCD approach.8 In continua-
tion, we have recently disclosed a new route for the preparation of
optically active steroids by kinetic resolution9 of (ꢀ)-spirolactone 1,
a key intermediate in our synthesis strategy. Excess of racemic
spirolactone 1 enolate has been acylated with bornyl carbonate and
* Corresponding author. Fax: þ33 491289112.
E-mail address: m.santelli@univ-cezanne.fr (M. Santelli).
reflux providing a mixture of steroids 5a–8, which were
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.10.073

178
D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
O
O
O
1. (TMS)2NLi
/ THF
(3 equiv.)
O
O
H
O
C
O
O
R*
R*
H
R1
R2
2. R*-CO2-R'*
(1 equiv.)
H
R1, R2 = H or MeO
( )-1 (3 equiv.)
(R,R) and (S,S)
in unequal proportions
Scheme 1. Lactone kinetic resolution by acylation.
isolated in high purity by chromatography on silica gel but with
substantial losses. For the major steroid 5a, we have checked
(as detailed in Section 4) that no racemization occurred in the
course of the Claisen condensation.
Steroids 5 and 6 arose from (S,S)-1, whereas steroids 7 and 8
coming from (R,R)-1 and the stereoselectivity of the acylation re-
action providing 2 was about 4.5:1. Steroids 5a,b or 7 with a trans B/C
ring junction resulted from a Diels–Alder reaction involving an exo
transition state, whereas steroids 6a,b or 8 including a cis B/C ring
junction arose from an endo transition state. All the steroids were of
C/D-cis derivatives. Active steroids as natural cardenolides have a C/
D-cis ring junction and it has been said that active components in the
Digitalisextracts have been ‘the mostingested drugs inmedicine’.12,13
In fact, only two steroids can be obtained from one enantiomer
of the spirolactone 1 since the alkylation reaction is stereoselective
giving rise to one benzocyclobutene 3a or 3b. Then, the cyclization
occurred with two transition states endo (cis B/C ring junction) or
exo (trans B/C ring junction). For example, 3a(S,S) was the result of
the alkylation of 2(S,S) and its thermolysis gave only 5a and 6a,
which are epimers at C(9). In this strategy, five stereogenic centers
(8, 11, 13, 14, and 17) are controlled in the course of the synthesis.
The proton NMR analysis has shown that for the steroids with
a trans B/C ring junction, the proton NMR coupling constant C(9)H–
C(8)H was in the range 9–12 Hz [C(9)H,
d¼2.90–3.90 ppm].
Fluoride-mediated deprotection of steroids 5–8 led to different
products according to the reagent used. Exposure of 5a or 5b to
O
O
O
O
O
S
TBDMSO
1. (TMS)2NLi
/ THF
S
(3 equivalents)
+
+
O
O
O
S
O
O
O
2.
OMe
R
TBDMSO
(1 equivalent)
TBDMSO
R
2, 60%
( )-1, 3 equiv.
O
O
R1
O
I
S
S
TBDMSO
R1
H
R2
a: R1 = OMe, R2 = H
b: R1 = H, R2 = OMe
H
H
R2
t-BuOK, KI / DMF
5a, 31%; 5b, 18%
O
O
O
O
O
S
O
O
S
TBDMSO
R1
TBDMSO
R1
H
O
H
H
R2
R2
Δ
+
6a, 11%; 6b, 41%
O
TBDMSO
O
O
S
R1
O
TBDMSO
MeO
R
H
R2
H
H
3a, 3b, 70%
+
7, 12%
H
H
Me
OH
O
Me
OH
O
O
O
O
O
S
O
TBDMSO
MeO
R
H
O
O
MeO
H
H
H
H
MeO
8, 13%
4a, 3.8%
4b, 5.1%
Scheme 2. Kinetic resolution of the (ꢀ)-spirolactone 1 and convergent synthesis of various 11-(S)-lactoyl-steroids.

D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
179
14
hydrogen fluoride–pyridine
gave spirolactones 9a or 9b, re-
Although natural steroids bearing a 17-vinyl group have been
isolated from soft coral15 or gorgonian,16 we have oxidized 13 to 17-
acetyl steroid 16 according to the Wacker process and previously
worked out procedure in our laboratory (Scheme 5).8a,17
spectively, coming from a trans-esterification (Scheme 3). X-ray
crystallographic analysis of 9a (Fig. 1) and 9b (Fig. 4) confirmed the
trans-anti-cis fused skeleton of 5a and 5b. In the same way, 6a and
6b gave rise to 10a and 10b, respectively, the cis–anti–cis ring
configuration of which was unambiguously confirmed by single
crystal X-ray analysis (Figs. 2 and 5). Finally, 7 and 8 gave rise to 11
and 12, respectively. Again, the trans–anti–cis configuration of 11
was also confirmed by crystal X-ray analysis (Fig. 3).
2.2. Kinetic resolution from methyl O-TBDMS (D)-(S)-
mandelate
The acylation of (ꢀ)-1 with O-TBDMS methyl (S)-(ꢁ)-mandelate
occurred in the fair yield of 85%. Then, it appears that the alkylation
with the 5-methoxy-1-iodobenzocyclobutene presented preferen-
tial reaction taking place mainly at the face of the enolate bearing
the vinyl group syn to the lactone bridge. It is the first example of
reverse stereoselectivity in the course of the alkylation of enolates
similar to 17.8,10,11 The geometrical constraints introduced by the
presence of the protected mandeloyl group can explain this re-
version of the stereochemistry. The structure of the minor isomer
18a was ascertained by X-ray crystallographic analysis (Fig. 7).
Thermolysis of 18 gave rise to three new steroids, the major, 20 and
the very minor, 19, coming from 1(R,R) and for the minor, 21, from
1(S,S) [(R,R)/(S,S)z3.3] (Scheme 6). The configuration has been
determined after deprotection by HF–pyridine and the structure of
22 was confirmed by X-ray crystallographic analysis (Fig. 8).
An attempt to induce a deprotection of 18b by HF–pyridine
before the thermolysis led to 24 resulting from a retro-Claisen re-
action with the loss of the mandeloyl moiety (Scheme 6).
In contrast, treatment of 5a by the tetrabutylammonium fluo-
ride led mainly to an 11
a decarboxylation reaction and a by-product 14 arising from
a retro-Claisen process. The -position of the lactoyl moiety of 13
b-lactoyl compound 13 resulting from
b
has been checked by crystal X-ray analysis (Fig. 6). In a same way,
6b led to 11-(S)-lactoyl-steroids 15 (Scheme 4).
S O
O
OH
HF - pyridine
/ THF
H
5a or 5b
R1
R2
O
H
H
9a, 60%; 9b, 45%
O
S
O
OH
HF - pyridine
/ THF
H
R1
R2
6a or 6b
O
H
H
Wacker-type oxidation of the 17b-vinyl group of 22 afforded the
17b-acetyl-steroid 25 in the fair yield of 57.4% (Scheme 7).
10a, 49%; 10b, 82%
2.3. Kinetic resolution from diacetone-D-glucose carbonate
S
O
OH
H
O
Finally, as in our previous works,10 we use an optically active
carbonate possessing a C2-axis of symmetry. Our choice has been
the diacetone-D-glucose carbonate 26 (DAG carbonate) obtained by
HF - pyridine
/ THF
7
H
O
MeO
H
reaction of the cheap and commercially available DAG with phos-
11, 41%
gene (Scheme 8).18
S
O
The acylation reaction occurred in the fair yield of 73% after 24 h
at ꢁ20 ꢂC. Once again, the alkylation by iodobenzocyclobutenes
took place at the face of the enolate bearing the vinyl group anti to
the lactone bridge. Thus, from an enantiomer of the lactone 1, five
stereogenic centers (8,11,13,14, and 17) are controlled in the course
of the synthesis. As from O-TBDMS methyl (S)-(ꢁ)-mandelate,
major steroids came from the 1(R,R) [(R,R)/(S,S)z2.5] (Scheme 9).
OH
H
O
HF - pyridine
/ THF
8
H
O
H
MeO
12, 38%
Scheme 3. Deprotection of steroids 5–8 with HF–pyridine.
C24
O25
C26
C23
O27
C12
C20
C21
O28
C2
O18
C11
C9
C1
C29
C19
O22
C10
C13
C14
C17
C3
C8
C16
C4
C5
C15
C7
C6
Figure 1. ORTEP diagram of compound 9a.

180
D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
O23
O18
C27
C24
C25
C21
C19
O22
C12
C13
C20
C17
O26
C11
C10
C2
C3
C1
C16
C14
C29
O28
C9
C15
C4
C6
C5
C7
C8
Figure 2. ORTEP diagram of compound 10a.
Interestingly, the steroid 29b was synthesized with an overall
carbonate, it is the contrary (methyl mandelate: (R,R)-1/(S,S)-
1¼3.3:1; DAG carbonate: (R,R)-1/(S,S)-1¼2.5). So, the O-TBDMS
methyl (ꢁ)-(S)-lactate and the 1(S,S) lithium enolate constitute
a ‘matched pair’ and the combination of O-TBDMS methyl (þ)-(S)-
mandelate or DAG-carbonate with the 1(R,R) lithium enolate leads
to another one. These results should be considered as examples of
double asymmetric induction.20
yield from spirolactone 1 of 24.3% and its isomer 30b of 9.9%.
In order to obtain a suitable crystallized compound for an X-ray
crystallographic analysis, the DAG moieties have been partially
hydrolyzed by treatment with acetic acid.19 Although this reaction
was not chemoselective, the new steroids were easily purified
(Scheme 10). Only, steroid 37 led to crystals able to give a good X-
ray crystallographic analysis (Fig. 9).
Attempts to obtain interesting crystals for an X-ray analysis by
esterification (tosylation or 3,5-dinitrobenzoylation) of diols 32–39
have failed (Scheme 11).
4. Experimental part
4.1. General
Finally, Wacker-type oxidation of the 17
b-vinyl group of 29b
afforded the 17 -acetyl-steroid 46. The DAG moiety was partially
hydrolyzed and a poor yield of 20% has been observed (Scheme 11).
b
All reactions were performed under an argon atmosphere in
oven-dried glassware. TLC was performed on silica gel 60 F254. Flash
chromatography was performed on silica gel (230–400 mesh)
obtained from Macherey-Nagel & Co. DMF and DMSO were distilled
before use from calcium hydride and THF was distilled from so-
dium/benzophenone. 1H and 13C NMR spectra were recorded at
25 ꢂC in CDCl3 solutions at 500 or 300, and 75 MHz, respectively,
using a Bruker AC300 and Advance DPX 500 spectrometers.
Chemical shift are reported in parts per million relative to CDCl3
3. Conclusion
From the absolute configuration of various obtained steroids, we
can conclude that with O-TBDMS methyl (ꢁ)-(S)-lactate, the lith-
ium enolate of (S,S)-1 was the most reactive [(S,S)-1/(R,R)-1[4.5:1]
and for the O-TBDMS methyl (þ)-(S)-mandelate and the DAG-
C24
O25
O27
C26
C23
C21
C20
O28
C2
C12
C13
C11
O18
C29
C1
O22
C9
C19
C17
C16
C10
C3
C14
C8
C5
C4
C15
C6
C7
Figure 3. ORTEP diagram of compound 11.

D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
181
C24
O25
C23
C26
O27
C21
O22
C12
C11
C1
C2
O18
C20
O5
C3
C10 C9
C19
C13
C17
C4
C28
C5
C8
C7
C14
C16
C15
C6
Figure 4. ORTEP diagram of compound 9b.
(signals for residual CDCl3 in CDCl3: 7.24 for 1H NMR and 77.16
(central) for 13C NMR). Carbon–proton couplings were determined
by DEPT sequence experiments. Spirolactone 1 (CAS number
149252-97-1), 1-iodo-4-methoxybenzocyclobutenes (CAS number
275367-67-4),8a 1-iodo-5-methoxybenzocyclobutenes (CAS num-
ber 270918-27-9),8a O-TBDMS methyl (ꢁ)-(S)-lactate (CAS number
87681-24-1), and O-TBDMS methyl (þ)-(S)-mandelate (CAS num-
ber 133187-21-0) were synthesized by the methods previously
described.
were dried on MgSO4. Solvent and pyridine were eliminated under
reduced pressure to give white solid of 26 (25 g, 46 mmol, 95%), mp
149 ꢂC. 1H NMR (300 MHz, CDCl3):
d
¼5.79 (d, J¼3.7 Hz, 1H), 5.11 (d,
J¼2.3 Hz, 1H), 4.50 (d, J¼3.7 Hz, 1H), 4.10–4.14 (m, 2H), 3.98–4.07
(m, 2H), 1.43 (s, 3H), 1.33 (s, 3H), 1.24 (s, 3H), 1.22 (s, 3H) ppm. 13C
NMR (75 MHz, CDCl3):
83.2 (d), 79.9 (d), 72.4 (d), 67.3 (t), 26.9 (q), 26.7 (q), 26.2 (q), 25.3
(q) ppm.
d
¼153.0 (s), 112.4 (s), 109.4 (s), 105.0 (d),
4.3. 3-[(S)-(2-tert-Butyldimethylsilyloxy)propanoyl]-6,9-
4.2. 1,2:5,6-Di-O-isopropylidene-
a
-D
-glucofuranose carbonate
divinyl-1-oxa-spiro[4,4]nonan-2-one (2)
(DAG carbonate) (26)
In a 500 mL three-neck flask equipped with a magnetic stirring
bar and a pressure-equalized addition funnel was added LiHMDS
(21.8 g, 0.13 mol) in 200 mL of anhydrous THF. The content was
stirred until dissolution and then cooled at ꢁ20 ꢂC. Racemic lactone
1 (25 g, 0.13 mol) in 43 mL of anhydrous THF was slowly added and
stirred for 20 min. The solution was cooled at ꢁ80 ꢂC and O-TBDMS
methyl (ꢁ)-(S)-lactate (9.4 g, 43 mmol) in 43 mL of anhydrous THF
was slowly added. After 1 h of stirring at ꢁ80 ꢂC, the solution was
stirred at ꢁ60 ꢂC for 20 h. The content was added to a chilled sat-
urated solution of NH4Cl. After extraction with Et2O, the organic
Phosgene is a hazardous compound and all the operations
should be performed under an efficient hood. To a stirred solution
of DAG (25 g, 96 mmol) in 250 mL of anhydrous CH2Cl2 was added
pyridine (12 g, 0.15 mol). The solution was cooled at ꢁ20 ꢂC and
a phosgene solution in toluene (ca. 20%, 23.5 g, 48 mmol) was
slowly added. After 1 h of stirring at ꢁ20 ꢂC, the solution was
allowed to stand at room temperature for 20 h. The reaction mix-
ture was added to a stirred saturated aqueous NaHCO3 solution. The
mixture was then extracted with CH2Cl2 and the organic layers
C25
O23
C24
C21
O18
C19
O22
C26
C12
C20
C13
C15
O27
C11
C9
C17
C1
C2
C10
C28
C14
C16
C8
C7
C3
O5
C5
C4
C6
Figure 5. ORTEP diagram of compound 10b.

182
D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
C25
O24
C20
C19
C17
C23
O22
C21
C12
C13
C14
C11
C9
O18
O26
C1
C2
C10
C16
C27
C3
C8
C15
C5
C4
C6
C7
Figure 6. ORTEP diagram of compound 13.
O
anhydrous DMF (63 mL) at 0 ꢂC. A solution of 2 (6 g, 15.8 mmol) in
anhydrous DMF (31.5 mL) and then solution of 1-iodo-5-
OH
S
HO
a
H
MeO
methoxybenzocyclobutene (5.34 g, 20.5 mmol) in anhydrous DMF
(31.5 mL) was added. The content was stirred for 2 days at room
temperature. The mixture was washed with water and the aqueous
phases extracted with Et2O, the organic layers were washed with
brine and dried over MgSO4, filtered, and concentrated under re-
duced pressure. The crude product was flash chromatographed on
silica gel (petroleum ether/Et2O 95:5 then 80:20) to give 3a (col-
orless oil, 5.64 g, 11.0 mmol, 70%)10 and 4a (mp 187 ꢂC, 238 mg,
0.6 mmol, 3.8%).10
H
H
13, 42%
(n-Bu)4NF, 3 H2O
5a
+
/ THF
O
O
H
H
H
MeO
H
14, 7%
O
OH
S
HO
(n-Bu)4NF, 3 H2O
4.5. 3-[(S)-(2-tert-Butyldimethylsilyloxy)propanoyl]-3-[4-
methoxybenzocyclobuten-1-yl]-6,9-divinyl-1-oxa-
spiro[4,4]nonan-2-one (3b)
6b
/ THF
H
H
MeO
15, 52%
Scheme 4. Deprotection of steroids 5–7 with (n-Bu)4NF.
The same procedure with 1-iodo-4-methoxybenzocyclobutene
led to 3b (colorless oil, 5.56 g, 10.9 mmol, 69%) and 4b (mixture of
isomers) (colorless oil, 320 mg, 0.8 mmol, 5.1%). Compound 3b. 13C
O
O
NMR (75 MHz, CDCl3) major isomer:
d
¼203.9 (s), 175.5 (s), 161.0 (s),
OH
Pd(OAc)2
S
HO
144.4 (s), 137.2 (d), 134.8 (d), 134.0 (s), 125.0 (d), 123.8 (d), 119.4 (t),
117.2 (t),114.7 (d),114.2 (d),108.8 (d), 94.4 (s), 70.7 (d), 68.7 (d), 63.4
(q), 55.5 (d), 55.4 (s), 53.0 (d), 52.5 (d), 46.4 (d), 38.2 (t), 31.9 (t), 27.4
(t), 27.0 (t), 25.7 (q), 21.5 (q), 18.1 (s), ꢁ4.4 (q) ppm. Compound 4b.
benzoquinone
H
13
MeO
MeCN / HClO4 - H2O
H
H
16, 60%
Scheme 5. Wacker-type oxidation of the vinyl group of 13.
13C NMR (75 MHz, CDCl3):
d
¼178.1 (s), 177.6 (s), 160.2 (s), 145.2 (s),
144.3 (s), 139.1 (d), 138.8 (d), 136.6 (s), 135.4 (s), 126.1 (d), 125.3 (d),
117.5 (d), 117.4 (d), 117.1 (d), 117.0 (t), 113.9 (d), 113.7 (d), 109.5 (s),
109.4 (s), 108.1 (d), 108.0 (d), 96.4 (s), 96.0 (s), 83.0 (d), 82.6 (d), 60.4
(s), 58.2 (s), 57.1 (s), 55.3 (d), 55.3 (d), 52.7 (d), 52.6 (d), 51.4 (d), 51.0
(d), 43.1 (d), 42.7 (d), 33.2 (t), 33.0 (t), 32.7 (t), 32.6 (t), 27.7 (t), 27.5
(t), 27.3 (t), 21.0 (q), 17.6 (q), 14.2 (q) ppm. C30H42O5Si (510.7): C
70.55, H 8.29; found C 70.67, H 8.21.
layers were washed with brine and dried over MgSO4, filtered, and
concentrated under reduced pressure. The crude product was flash
chromatographed on silica gel (petroleum ether/Et2O 97:3) to give
2 (12 g, 31.4 mmol, 73%).10
4.4. 3-[(S)-(2-tert-Butyldimethylsilyloxy)propanoyl]-3-
[5-methoxybenzocyclobuten-1-yl]-6,9-divinyl-1-oxa-
spiro[4,4]nonan-2-one (3a)
4.6. General procedure for the thermolysis of 3, 18, and 28
Steroid precursors 1 mmol in 1,2,4-trichlorobenzene (10 mL/
mmol) were heated at reflux (214 ꢂC) for 20–24 h (the progress of
the reaction was followed by TLC analysis). The solvent was re-
moved under reduced pressure and the residue was flash chro-
matographed on silica gel.
In a 250 mL two-neck flask equipped with a magnetic stirring
bar and a pressure-equalized addition funnel was added potassium
tert-butylate (2.3 g, 20.5 mmol) and KI (3.4 g, 20.5 mmol) in

D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
183
C27
C26
C25
C28
C35
C33
C9
C3
C10
O2
C29
C24
C23
C32
Si1
C7
C8
O1
C34
C22
C6
C4
O5
C30
O4
C1
C5
C2
C15
C31
C13
C20
C21
O3
C11
C12
C14
C19
C16
C17
C18
Figure 7. ORTEP diagram of compound 18a.
1. (TMS)2NLi
/ THF
O
O
O
O
O
O
(3 equivalents)
( )-1
S
+
S
TBDMSO
TBDMSO
O
(3 equiv.)
Ph
Ph
S
Ph
2.
OMe
17, 85%
TBDMSO
(1 equivalent)
S
I
TBDMSO
Ph
O
MeO
O
O
R
H
H
t-BuOK, KI / DMSO
MeO
H
H
TBDMSO
Ph
O
19, 4%
O
S
RO
Ph
O
O
MeO
H
O
H
O
R
Δ
MeO
+
18a, 12%
H
TBDMSO
Ph
O
O
20, R = TBDMS, 38%;
O
HF - pyridine
/ THF
MeO
22, R = H
S
RO
Ph
18b, 38%
O
HF - pyridine
/ THF
O
O
S
H
MeO
O
O
H
H
MeO
21, R = TBDMS, 12%;
HF - pyridine
/ THF
23, R = H
24, 80%
Scheme 6. Kinetic resolution of the (ꢀ)-spirolactone 1 and convergent synthesis of various 11-(S)-mandeloyl steroids.

184
D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
C28
C27
C29
C24
C26
C25
C19
O5
C23
C22
C12
C18
O4
C11
C13
C20
O1
C17
O2
C9
C21
O3
C1
C10
C16
C2
C14
C15
C8
C3
C5
C7
C6
C4
Figure 8. ORTEP diagram of compound 22.
S
HO
O
Ph
O
O
O
Pd(OAc)2
(m, 3H), 1.66 (qd, J¼12.1, 5.5 Hz, 1H), 1.53 (br qd, J¼10.9, 3.4 Hz, 1H),
1.39 (d, J¼6.65 Hz, 3H), 1.27 (dd, J¼11.3, 7.3 Hz,1H), 0.96 (qd, J¼12.0,
5.65 Hz, 1H), 0.71 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H) ppm. 13C NMR
benzoquinone
22
H
MeCN / HClO4 - H2O
MeO
H
H
(75 MHz, CDCl3):
d¼208.9 (s), 175.8 (s), 157.8 (s), 143.5 (s), 135.4 (d),
129.6 (d), 129.2 (s), 117.1 (t), 110.5 (d), 110.2 (d), 93.0 (s), 75.3 (d),
60.7 (s), 55.3 (q), 53.3 (d), 51.2 (d), 44.9 (d), 43.5 (d), 35.9 (t), 31.9 (t),
30.8 (t), 26.7 (t), 26.7 (t), 25.9 (q)(3C), 21.4 (q),18.1 (s), ꢁ4.0 (q), ꢁ5.3
(q) ppm. C30H42O5Si (510.7): C 70.55, H 8.29; found C 70.46, H 8.32.
24
Scheme 7. Wacker-type oxidation of the vinyl group of 22.
H
H
H
H
H
O
O
O
O
O
O
4.6.1.2. (8
yl]-11 ,13
triene (6a). Colorless oil, [
b
,9
-(
b
,14
a)-11b-[2(S)-(tert-Butyldimethylsilyloxy)propano-
O
O
a
a
g
-carbolactone)-2-methoxy-17a-vinylgona-1,3,5(10)-
O
O
H
H
20
a
]
ꢁ54 (c 0.31, CH2Cl2). 1H NMR
H
O
D
HO
O
pyridine
CH2Cl2
(300 MHz, CDCl3):
d
¼6.88 (d, J¼8.3 Hz, 1H), 6.60 (dd, J¼8.5, 1.4 Hz,
DAG
+
O
1H), 6.42 (br s, 1H), 5.87 (br quint, J¼8.92 Hz, 1H), 5.09 (br d,
J¼17.0 Hz, 1H), 5.05 (br d, J¼10.4 Hz,1H), 4.77 (q, J¼6.9 Hz,1H), 4.53
(br d, J¼5.6 Hz), 3.65 (s, 3H), 3.16 (d, J¼11.6 Hz, 1H), 2.64–2.74 (m,
2H), 3.02 (d, J¼11.4 Hz, 1H), 2.70 (1⁄2 AB, J¼11.5 Hz, 1H), 2.43–2.51
(m, 3H), 2.24 (1⁄2 AB, J¼11.4 Hz, 1H), 2.12–2.18 (m, 2H), 1.76–1.87
(m, 3H), 1.70 (d, J¼7.0 Hz, 1H), 1.58 (d, J¼7.0 Hz, 3H), 0.88 (s, 9H),
H
H
H
O
O
O
O
O
O
H
Cl
Cl
DAG-Carbonate, 26, 95%
Scheme 8. Synthesis of diacetone-D-glucose carbonate 26.
0.12 (s, 3H), 0.11 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼209.7 (s),
172.8 (s), 157.1 (s), 136.0 (d), 134.9 (s), 129.9 (d), 129.2 (s), 116.9 (t),
115.6 (d), 112.9 (d), 91.9 (s), 76.2 (d), 61.0 (s), 55.4 (q), 51.8 (d), 46.1
(d), 40.0 (t), 39.1 (d), 35.2 (d), 32.0 (t), 30.5 (t), 26.1 (q)(3C), 25.6 (t),
24.1 (t), 22.7 (q),18.3 (s), ꢁ3.3 (q), ꢁ4.7 (q) ppm. C30H42O5Si (510.7):
C 70.55, H 8.29; found C 70.60, H 8.36.
4.6.1. Thermolysis of 3a
From 3a (8 g, 15.7 mmol): 5a (2.48 g, 4.86 mmol, 31%), 6a
(880 mg, 1.7 mmol, 11%), 7 (936 mg, 1.84 mmol, 12%) after flash
chromatography (EP/AcOEt 98:2).
4.6.1.1. (8
yl]-11 ,13
triene (5a). Colorless oil, [
(500 MHz, CDCl3):
1H), 6.38 (d, J¼2.2 Hz, 1H), 5.86 (ddd, J¼17.0, 10.2, 8.3 Hz, 1H), 5.10
(br d, J¼17.0 Hz, 1H), 5.09 (br d, J¼10.2 Hz, 1H), 4.70 (q, J¼6.6 Hz,
1H), 3.68 (s, 3H), 3.35 (d, J¼11.2 Hz,1H), 2.80 (1⁄2 AB, J¼12.5 Hz,1H),
2.74 (q, J¼8.4 Hz, 1H), 2.68–2.74 (m, 1H), 2.45 (dt, J¼11.5, 7.4 Hz,
1H), 2.22 (1⁄2 AB, J¼12.4 Hz, 1H), 2.04 (qd, 6.0, 1.0 Hz, 1H), 1.83–1.96
b
,9
-(
a
,14
a
)-11
b
-[2(S)-(tert-Butyldimethylsilyloxy)propano-
4.6.1.3. (8
yl]-11 ,13
a
,9
b
g
,14b)-11a-[2(S)-(tert-Butyldimethylsilyloxy)propano-
a
a
g
-carbolactone)-2-methoxy-17
a
-vinylgona-1,3,5(10)-
b
b
-(
-carbolactone)-2-methoxy-17b-vinylgona-1,3,5(10)-
ꢁ65 (c 0.2, CH2Cl2). 1H NMR
triene (7). Colorless oil, [
CDCl3):
20
20
a
]
a]
D
þ12 (c 0.4, CH2Cl2). 1H NMR (500 MHz,
D
d
¼6.99 (d, J¼8.2 Hz, 1H), 6.62 (dd, J¼8.2, 2.4 Hz,
d
¼6.98 (d, J¼8.3 Hz,1H), 6.60 (dd, J¼8.3, 2.4 Hz,1H), 6.21 (d,
J¼2.2 Hz,1H), 5.90 (ddd, J¼16.4,10.7, 8.6 Hz,1H), 5.105 (d, J¼16.8 Hz,
1H), 5.10 (d, J¼10.9 Hz,1H), 4.81 (q, J¼6.5 Hz,1H), 3.67 (s, 3H), 3.17 (d,
J¼10.8 Hz, 1H), 2.82 (1⁄2 AB, J¼12.0 Hz, 1H), 2.72–2.75 (m, 2H), 2.45
(dt, J¼10.9, 7.6 Hz, 1H), 2.32 (1⁄2 AB, J¼12.0 Hz, 1H), 2.07 (br quint,
J¼6.22 Hz, 1H), 1.84–1.92 (m, 2H), 1.65 (qd, J¼11.7, 5.5 Hz, 1H), 1.44–

D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
185
1. (TMS)2NLi
/ THF
O
O
O
O
O
O
(3 equivalents)
( )-1
+
DAG O
DAG O
2. 26 (1 equiv.)
(3 equiv.)
27, 73%
R1
R2
I
O
O
O
O
O
H
H
H
H
O
H
a: R1 = OMe, R2 = H
b: R1 = H, R2 = OMe
R
O
H
H
R1
H
Cs2CO3 - KI / acetone
O
O
H
R2
O
O
29a, 41%; 29b, 49%
DAG O
O
O
O
R1
R2
O
O
O
O
H
O
Δ
S
+
O
H
H
R1
O
H
DAG O
O
O
H
H
R2
O
R1
R2
30a, 21%; 30b, 20%
O
O
O
O
28a, 28b, 80 - 85%
O
H
O
R
O
MeO
H
O
H
H
H
H
O
31, 13%
Scheme 9. Kinetic resolution of the (ꢀ)-spirolactone 1 and convergent synthesis of various steroids from DAG carbonate.
1.48 (m, 2H), 1.38 (d, J¼6.6 Hz, 3H), 1.02 (qd, J¼11.8, 5.7 Hz, 1H), 0.85
43.7 (d), 36.3 (t), 31.9 (t), 30.7 (t), 28.1 (t), 26.6 (t), 25.9 (q)(3C), 21.4
(q), 18.1 (s), ꢁ4.1 (q), ꢁ5.0 (q) ppm. C30H42O5Si (510.7): C 70.55, H
8.29; found C 70.46, H 8.22.
(s, 9H), 0.09 (s, 3H), 0.05 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼205.4 (s),176.3 (s),157.4 (s),135.7 (d),135.7 (s),129.9 (s),129.6 (d),
117.1 (t), 112.5 (d), 110.6 (d), 93.2 (s), 74.1 (d), 59.2 (s), 55.4 (q), 52.9
(d), 51.4 (d), 45.6 (d), 42.7 (d), 37.7 (t), 31.9 (t), 30.2 (t), 27.5 (t), 27.2 (t),
26.1 (q)(3C), 20.0 (q), 18.4 (s), ꢁ4.4 (q), ꢁ4.5 (q) ppm. C30H42O5Si
(510.7): C 70.55, H 8.29; found C 70.44, H 8.26.
4.6.2.2. (8
11 ,13 -(
(6b). Colorless oil, [
CDCl3):
b b,14a)-11b-[2(S)-(tert-Butyldimethylsilyloxy)propanoyl]-
,9
a
a
g
-carbolactone)-3-methoxy-17a-vinylgona-1,3,5(10)-triene
20
a
]
ꢁ70.8 (c 0.12, CH2Cl2). 1H NMR (500 MHz,
D
d
¼6.76 (d, J¼8.7 Hz, 1H), 6.59 (dd, J¼8.7, 2.7 Hz, 1H), 6.50 (d,
4.6.1.4. Determination of the enantiomeric excess of 5a. The enan-
tiomeric excess of 5awas determined by HPLC analysis [CHIRALPAK-
AD, hexane/2-propanol 95:5, 1 mL/min, 254 nm, polarimeter]:
(ꢁ)-5a, 97.6%, (þ)-5a, 2.4%. Thiseewas identical of this commercially
available purum methyl (ꢁ)-(S)-lactate (Fluka).
J¼2.6 Hz, 1H), 5.87 (ddd, J¼17.2, 10.0, 8.6 Hz, 1H), 5.08 (d, J¼16.3 Hz,
1H), 5.05 (d, J¼10.0 Hz, 1H), 4.86 (q, J¼6.9 Hz, 1H), 4.49 (d, J¼7.2 Hz,
1H), 3.70 (s, 3H), 2.79 (q, J¼8.6 Hz, 1H), 2.57 (1⁄2 AB, J¼11.5 Hz, 1H),
2.45–2.51 (m, 2H), 2.26 (1⁄2 AB, J¼11.5 Hz, 1H), 2.07–2.21 (m, 3H),
1.83–1.89 (m, 3H),1.60–1.69 (m, 2H),1.53 (d, J¼6.9 Hz, 3H),1.05–1.15
(m, 2H), 0.89 (s, 9H), 0.11 (s, 6H) ppm. 13C NMR (75 MHz, CDCl3):
4.6.2. Thermolysis of 3b
d
¼209.3 (s),173.3 (s),157.6 (s),138.3 (s),135.9 (d),131.4 (d),125.6 (s),
From 3b (2 g, 3.9 mmol): 5b (360 mg, 0.7 mmol, 18%), 6b
(820 mg, 1.6 mmol, 41%), 8 (260 mg, 0.5 mmol, 13%) after flash
chromatography (EP/AcOEt 90:10).
116.9 (t), 113.6 (d), 111.7 (d), 91.9 (s), 75.6 (d), 60.8 (s), 55.2 (q), 51.7
(d), 46.2 (d), 40.0 (t), 39.0 (d), 35.2 (d), 31.9 (t), 30.6 (t), 26.1 (q)(3C),
25.3 (t), 25.2 (t), 22.3 (q),18.3 (s), ꢁ3.6 (q), ꢁ4.7 (q) ppm. C30H42O5Si
(510.7): C 70.55, H 8.29; found C 70.52, H 8.26.
4.6.2.1. (8
yl]-11 ,13
iene (5b). Colorless oil,
(500 MHz, CDCl3):
b
,9
g
a
,14
a)-11b-[2(S)-(tert-Butyldimethylsilyloxy)propano-
a
a-(
-carbolactone)-3-methoxy-17
a
-vinylgona-1,3,5(10)-tr-
4.6.2.3. (8
11 ,13 -(
(8). Colorless oil, [
CDCl3):
a
,9
a
,14
b
)-11
a
-[2(S)-(tert-Butyldimethylsilyloxy)propanoyl]-
-vinylgona-1,3,5(10)-triene
a]
24.7 (c 0.15, CH2Cl2). 1H NMR (300 MHz,
D
20
[
a]
ꢁ43 (c 0.52,CH2Cl2). 1H NMR
b
b
g
-carbolactone)-3-methoxy-17b
D
20
d
¼6.66 (br s, 1H), 6.65 (d, J¼8.5 Hz, 1H), 6.55 (dd,
J¼8.5, 2.7 Hz, 1H), 5.84 (ddd, J¼16.6, 10.6, 8.4 Hz, 1H), 5.15 (br d,
J¼17.1 Hz, 1H), 5.10 (br d, J¼10.2 Hz, 1H), 4.69 (q, J¼6.7 Hz, 1H), 3.73
(s, 3H), 3.27 (d, J¼11.1 Hz, 1H), 2.73–2.84 (m, 2H), 2.44 (dt, J¼11.7,
7.2 Hz, 1H), 2.21 (1⁄2 AB, J¼12.5 Hz, 1H), 2.04 (br quint, J¼6.4 Hz,
1H), 1.85–1.94 (m, 3H), 1.65 (qd, J¼11.9, 5.5 Hz, 1H), 1.48–1.56 (m,
2H), 1.35 (d, J¼6.7 Hz, 3H), 1.28 (dd, J¼11.3, 7.0 Hz, 1H), 0.97 (qd,
J¼11.7, 5.7 Hz, 1H), 0.84–0.91 (m, 2H), 0.74 (s, 9H), 0.07 (s, 3H), 0.05
d
¼6.68 (d, J¼8.2 Hz,1H), 6.57 (dd, J¼8.2, 2.6 Hz,1H), 6.46 (d,
J¼2.6 Hz, 1H), 5.87 (ddd, J¼17.0, 10.1, 8.6 Hz, 1H), 5.08–5.00 (m, 2H),
4.79 (q, J¼6.45 Hz, 1H), 4.44 (br d, J¼5.82 Hz, 1H), 3.70 (s, 3H), 3.19
(d, J¼11.6 Hz), 3.09 (d, J¼11.5 Hz), 2.90 (1⁄2 AB, J¼11.5 Hz, 1H), 2.64–
2.80 (m, 2H), 2.38–2.50 (m, 2H), 2.26 (1⁄2 AB, J¼11.4 Hz, 1H), 2.0 (m,
2H), 1.80–1.86 (m, 2H), 1.65 (1H, m), 1.54–1.66 (m, 1H), 1.43 (d,
J¼6.5 Hz, 3H), 0.86 (s, 9H), 0.09 (s, 6H) ppm. 13C NMR (75 MHz,
(s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼208.2 (s), 176.2 (s), 157.9
CDCl3):
d
¼208.1 (s), 176.1 (s), 157.8 (s), 139.1 (s), 135.4 (d), 134.0 (d),
(s), 139.2 (s), 135.5 (d), 134.1 (s), 124.7 (d), 117.1 (t), 114.7 (d), 110.4
(d), 93.1 (s), 75.5 (d), 60.2 (s), 55.4 (q), 53.1 (d), 51.3 (d), 44.6 (d),
124.6 (s), 117.0 (t), 114.6 (d), 110.3 (d), 93.1 (s), 75.4 (d), 60.1 (s), 55.3
(q), 53.0 (d), 51.2 (d), 44.5 (d), 43.6 (d), 36.2 (t), 31.8 (t), 30.6 (t), 28.1

186
D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
OH OH
O
O
O
O
O
O
H
H
O
H
H
H
O
H
O
O
O
St
H
29a
+
+
O
H
H
H
MeO
O
H
OH
O
H
32, 54%
33, 10%
OH
OH OH
O
O
O
O
H
H
O
H
O
H
O
St
H
30a
O
H
H
H
H
MeO
O
H
OH
O
H
34, 32%
35, 12%
OH
O
O
O
O
O
H
H
O
H
31
O
H
MeO
H
OH
H
36, 49%
OH
OH OH
O
O
O
O
O
H
H
O
O
H
H
H
O
O
St
H
29b
+
O
H
H
H
O
H
H
OH
O
37, 54%
38, 10%
OH
MeO
O
O
O
O
O
H
H
O
H
30b
O
H
H
H
OH
H
39, 45%
OH
MeO
Scheme 10. Partial hydrolysis of the DAG moieties of steroids 29–31.
O41
C30
O40
C27
C23
C29
O39
O37
C22
C26
O38
C24
O36
C25
C28
C18
O35
C12
C21
C11
C17
C13
O33
C20
C19
O34
C9
C1
C10
C2
O42
C16
C8
C15
C14
C5
C3
C6
C4
C31
C7
Figure 9. ORTEP diagram of compound 37.

D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
187
d
¼6.96 (d, J¼8.4 Hz, 1H), 6.64 (dd, J¼8.4, 2.4 Hz, 1H), 6.56 (d,
J¼2.13 Hz, 1H), 5.93 (ddd, J¼17.3, 10.2, 8.2 Hz, 1H), 5.07 (dd, J¼10.2,
1.6 Hz, 1H), 5.0 (d, J¼17.3 Hz, 1H), 4.28 (q, J¼7.1 Hz, 1H), 3.69 (s, 3H),
3.60 (d, J¼10.1 Hz,1H), 3.32 (s, OH,1H), 2.58–2.66 (m, 2H), 2.10–2.19
(m, 2H), 1.98–2.03 (m, 1H), 1.99 (1⁄2 AB, J¼14.3 Hz, 1H), 1.87 (1⁄2 AB,
J¼14.8 Hz, 1H), 1.82–1.88 (m, 2H), 1.77 (quint, J¼6.0 Hz, 1H), 1.67
(qd, J¼12.1, 5.8 Hz, 1H), 1.38 (d, J¼7.1 Hz, 3H), 1.19–1.24 (m,
O
O
O
O
Pd(OAc)2
O
O
H
H
O
H
benzoquinone
29b
O
H
MeCN
/ HClO4 - H2O
H
H
OH
H
OH
MeO
40
2H) ppm. 13C NMR (75 MHz, CDCl3):
d¼212.0 (s), 181.1 (s), 158.1 (s),
Scheme 11. Wacker-type oxidation of the vinyl group of 29b.
137.9 (d), 135.2 (s), 131.5 (d), 131.03 (s), 116.0 (t), 113.1 (d), 110.7 (d),
82.3 (d), 79.0 (s), 56.8 (d), 56.4 (d), 55.3 (q), 52.4 (s), 46.6 (d), 41.1 (t),
38.2 (d), 30.6 (t)(2C), 29.5 (t), 27.8 (t), 17.0 (q) ppm. C24H28O5
(396.5): C 72.70, H 7.12; found C 72.88, H 7.18.
(t), 26.5 (t), 25.9 (q)(3C), 21.4 (q), 18.1 (s), ꢁ4.1 (q), ꢁ5.0 (q) ppm.
C30H42O5Si (510.7): C 70.55, H 8.29; found C 70.48, H 8.21.
4.7.4. (8
-carboxylic acid-
triene (9b)
From 5b: 45% yield after 24 h of stirring. White crystals, mp
b
,9
a
,14
a
)-13
a
-Hydroxy-[11
b
-(2(S)-hydroxypropanoyl)-11-
4.7. General procedure for the deprotection of alcohols by
HF–pyridine
a
g-lactone]-3-methoxy-17
a-vinylgona-1,3,5(10)-
20
To a stirred solution of 1 mmol of O-TBDMS-steroid in THF
(15 mL/mmol) at 0 ꢂC was slowly added HF–pyridine solution
(1.3 mL/mmol). Then, the solution was stirred at room temperature
and the progress of the reaction was followed by TLC analysis. The
reaction mixture was quenched with water and diluted with Et2O.
NaHCO3 saturated solution was added to this stirred mixture until
neutrality. After extraction with Et2O, the organic extract was dried
over MgSO4, filtered, and concentrated under reduced pressure.
The crude product was flash chromatographed on silica gel (pe-
troleum ether/AcOEt 80:20).
165 ꢂC, [
a
]
D
143.8 (c 0.24, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
¼6.80 (d, J¼9.4 Hz, 1H), 6.59 (d, J¼9.4 Hz, 1H), 6.58 (s, 1H), 5.90
(ddd, J¼17.3, 10.2, 8.1 Hz, 1H), 5.08 (dd, J¼10.2, 1.9 Hz, 1H), 4.98 (br
dt, J¼17.3, 0.9 Hz, 1H), 4.73 (q, J¼7.0 Hz, 1H), 3.72 (s, 3H), 3.56 (d,
J¼10.7 Hz,1H), 2.86 (s, OH,1H), 2.66 (dt, J¼16.1, 2.1 Hz,1H), 2.70 (dt,
J¼14.3, 2.5 Hz, 2H), 2.12 (1⁄2 AB, J¼14.4 Hz, 1H), 1.98–2.22 (m, 2H),
1.90 (dd, J¼11.3, 2.7 Hz, 1H), 1.84 (1⁄2 AB, J¼14.4 Hz, 1H), 1.64–1.84
(m, 3H), 1.20–1.30 (m, 2H), 1.19 (d, J¼7.0 Hz, 3H) ppm. 13C NMR
(75 MHz, CDCl3):
d
¼211.9 (s), 180.4 (s), 158.0 (s), 140.7 (s), 137.6 (d),
127.6 (d), 127.4 (s), 116.5 (t), 114.4 (d), 112.5 (d), 80.5 (d), 79.6 (s),
56.5 (d), 56.3 (d), 55.3 (q), 53.2 (s), 43.9 (d), 41.6 (t), 38.8 (d), 30.7 (t),
30.4 (t), 30.3 (t), 27.9 (t), 15.0 (q) ppm. C24H28O5 (396.5): C 72.70, H
7.12; found C 72.59, H 7.18.
4.7.1. (8
11 -carboxylic acid-
1,3,5(10)-triene (9a)
From 5a: 60% yield after 4.5 days of stirring. White crystals, mp
171 ꢂC, [ 20 188 (c 0.13, CH2Cl2). 1H NMR (300 MHz, CDCl3):
¼6.95
b,9
a,14
a)-13
a
-Hydroxy-[11
b
-(2(S)-hydroxypropanoyl)-
a
g
-lactone]-2-methoxy-17a-vinylgona-
4.7.5. (8
11 -carboxylic acid-
1,3,5(10)-triene (10b)
From 6b: 82% yield after 3 days of stirring. White crystals, mp
175 ꢂC, [ 20 46.5 (c 1.15, CH2Cl2). 1H NMR (300 MHz, CDCl3):
¼6.59
b
,9b
,14
a)-13
a
-Hydroxy-[11
b
-(2(S)-hydroxypropanoyl)-
a
]
D
d
a
g-lactone]-3-methoxy-17
a-vinylgona-
(d, J¼8.4 Hz, 1H), 6.60 (dd, J¼8.4, 2.3 Hz, 1H), 6.41 (d, J¼1.9 Hz, 1H),
5.87 (ddd, J¼17.3, 10.2, 8.2, Hz, 1H), 5.08 (br d, J¼10.3 Hz, 1H), 4.99
(br d, J¼17.2 Hz, 1H), 4.75 (q, J¼7.0 Hz, 1H), 3.68 (s, 3H), 3.57 (d,
J¼10.4 Hz, 1H), 2.58–2.80 (m, 2H), 2.12 (1⁄2 AB, J¼14.3 Hz, 1H), 2.0–
2.22 (m, 2H), 1.84 (1⁄2 AB, J¼14.6 Hz, 1H), 1.76–1.92 (m, 1H), 1.74 (td,
J¼6.4, 1.2 Hz, 1H), 1.68 (1⁄2 AB, d, J¼11.9, 5.9 Hz, 1H), 1.21 (d,
a
]
D
d
(d, J¼2.5 Hz, 1H), 6.55 (dd, J¼8.5, 2.6 Hz, 1H), 6.42 (d, J¼8.5 Hz, 1H),
5.89 (ddd, J¼17.06, 10.5, 8.18 Hz, 1H), 5.07 (br d, J¼10.4 Hz, 1H), 5.04
(br d, J¼17.0 Hz, 1H), 4.99 (q, J¼7.0 Hz, 1H), 3.84 (d, J¼8.1 Hz), 3.71
(s, 3H), 2.93 (dd, J¼11.3, 4.1 Hz, 1H), 2.87 (dd, J¼11.3, 4.1 Hz, 1H),
2.36–2.54 (m, 2H), 2.12–2.23 (m, 3H), 2.05 (1⁄2 AB, J¼14.4 Hz, 1H),
1.84–1.92 (m, 2H), 1.83 (1⁄2 AB, J¼14.3 Hz, 1H), 1.65–1.77 (m, 2H),
1.55 (d, J¼7.0 Hz, 1H), 1.32–1.39 (m, 2H) ppm. 13C NMR (75 MHz,
J¼7.0 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3):
¼211.6 (s), 180.2 (s),
d
157.9 (s), 137.6 (d), 136.2 (s), 131.1 (s), 130.8 (d), 116.3 (t), 112.2 (d),
111.8 (d), 80.4 (d), 79.6 (s), 56.4 (d), 56.3 (d), 55.2 (q), 53.2 (s), 44.5
(d), 41.6 (t), 38.6 (d), 30.4 (t), 30.2 (t), 29.4 (t), 28.1 (t), 14.7 (q) ppm.
C24H28O5 (396.5): C 72.70, H 7.12; found C 72.85, H 7.08.
CDCl3):
d
¼212.9 (s), 176.3 (s), 158.0 (s), 140.6 (s), 137.0 (d), 128.0 (s),
127.6 (d), 116.7 (t), 114.2 (d), 112.4 (d), 79.63 (s or d), 79.58 (s or d),
56.1 (s), 55.8 (d), 55.2 (q), 47.7 (d), 42.2 (d), 39.7 (t), 36.8 (d), 29.7 (t),
29.3 (t), 25.8 (t), 25.2 (t), 16.1 (q) ppm. C24H28O5 (396.5): C 72.70, H
7.12; found C 72.69, H 7.19.
4.7.2. (8
11 -carboxylic acid-
1,3,5(10)-triene (10a)
From 6a: 49% yield after 24 h of stirring. White crystals, mp
171 ꢂC, [ 20 46 (c 0.11, CH2Cl2). 1H NMR (300 MHz, CDCl3):
¼6.99
b
,9b
,14
a)-13a-Hydroxy-[11
b-(2(S)-hydroxypropanoyl)-
a
g
-lactone]-2-methoxy-17a-vinylgona-
a]
d
4.7.6. (8
11 -carboxylic acid-
1,3,5(10)-triene (12)
a
,9
a
,14
b
)-13
b
-Hydroxy-[11
a
-(2(S)-hydroxypropanoyl)-
-vinylgona-
D
(d, J¼8.4 Hz, 1H), 6.61 (dd, J¼8.4, 2.5 Hz, 1H), 6.04 (d, J¼2.4 Hz, 1H),
5.89 (ddd, J¼17.0, 10.6, 8.2 Hz, 1H), 5.00–5.09 (m, 2H), 3.86 (d,
J¼8.2 Hz, 1H), 3.66 (s, 3H), 2.83 (ddd, J¼15.8, 11.8, 3.8 Hz, 1H), 2.39–
2.50 (m, 2H), 2.09–2.19 (m, 3H), 2.06 (1⁄2 AB, J¼14.3 Hz, 1H), 1.80–
1.90 (m, 2H), 1.80 (1⁄2 AB, J¼14.4 Hz, 1H), 1.70–1.77 (m, 2H), 1.61 (d,
J¼7.0 Hz, 3H), 1.31–1.45 (m, 2H) ppm. 13C NMR (75 MHz, CDCl3):
b
g
-lactone]-3-methoxy-17b
From 8: 38% yield after 3 days of stirring. White crystals, mp
20
168 ꢂC, [
d
a]
D
ꢁ13 (c 0.05, CH2Cl2). 1H NMR (300 MHz, CDCl3):
¼6.59 (s, 1H), 6.55 (d, J¼2.6 Hz, 2H), 5.94 (ddd, J¼16.9, 10.6, 8.3 Hz,
1H), 5.06 (br, J¼10.0 Hz, 1H), 5.04 (br d, J¼17.0 Hz, 1H), 4.69 (q,
J¼7.1 Hz, 1H), 3.76 (s, 3H), 3.68 (d, J¼7.3 Hz, 1H), 3.24 (s, OH, 1H),
2.88 (1⁄2 AB, dd, J¼16.8, 8.5, 5.2 Hz, 1H), 2.53 (1⁄2 AB, t, J¼16.8,
5.8 Hz, 1H), 2.40 (quint, J¼8.45 Hz, 1H), 2.27 (q, J¼8.2 Hz, 1H), 2.02–
2.10 (m, 1H), 1.91–1.96 (m, 1H), 1.89 (d, J¼5.2 Hz, 2H), 1.79–1.82 (m,
2H),1.62–1.69 (m, 2H),1.40–1.51 (m,1H),1.50 (d, J¼7.1 Hz, 3H) ppm.
d
¼212.7 (s),176.2 (s),157.9 (s),136.9 (d),135.1 (s),131.2 (s),130.5 (d),
116.8 (t), 113.4 (d), 111.1 (d), 84.0 (d), 79.6 (s), 56.0 (d), 55.4 (q), 47.5
(d), 42.4 (d), 40.6 (t), 36.6 (d), 29.8 (t), 29.3 (t), 25.3 (t), 24.3 (t), 16.1
(q) ppm. C24H28O5 (396.5): C 72.70, H 7.12; found C 72.75, H 7.24.
4.7.3. (8
11 -carboxylic acid-
1,3,5(10)-triene (11)
a
,9
b
,14
b
)-13
b
-Hydroxy-[11
a
-(2(S)-hydroxypropanoyl)-
13C NMR (75 MHz, CDCl3):
d
¼214.5 (s), 177.7 (s), 158.4 (s), 140.4 (s),
b
g
-lactone]-2-methoxy-17
b-vinylgona-
137.9 (d), 128.0 (d), 127.0 (s), 115.9 (t), 114.3 (d), 112.5 (d), 81.7 (d),
78.4 (s), 55.5 (d), 55.2 (q), 55.1 (s), 47.6 (d), 42.2 (d), 41.0 (t), 36.5 (d),
28.92 (t), 28.83 (t), 26.7 (t), 25.0 (t), 17.9 (q) ppm. C24H28O5 (396.5):
C 72.70, H 7.12; found C 72.79, H 7.22.
From 7: 41% yield after 2.5 days of stirring. White crystals, mp
20
171 ꢂC, [
a]
ꢁ237 (c 0.24, CH2Cl2). 1H NMR (500 MHz, CDCl3):
D

188
D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
4.8. General procedure for the deprotection of alcohols by
tetrabutylammonium fluoride trihydrate
J¼2.4 Hz, 1H), 6.62 (dd, J¼8.3, 2.45 Hz, 1H), 4.08 (br qd, J¼7.03,
3.27 Hz, 1H), 3.96 (s, 1H), 3.88 (q, J¼7.00 Hz, 1H), 3.68–3.75 (m,
1H), 3.73 (s, 3H), 3.25 (br d, J¼3.77 Hz, 1H), 3.09 (dd, J¼11.1,
6.7 Hz, 1H), 2.85 (dd, J¼11.3, 7.6 Hz, 1H), 2.60–2.80 (m, 2H), 2.16–
2.25 (m, 2H), 2.25 (1⁄2 AB, J¼16.3, 1H), 2.20 (s, 3H), 2.15 (1⁄2 AB,
J¼16.3, 1H), 1.90–2.11 (m, 3H), 1.40–1.48 (m, 1H), 1.35 (d,
J¼7.11 Hz, 3H), 1.1 (qd, J¼12.3, 4.7 Hz, 1H) ppm. 13C NMR
To a stirred solution of 1 mmol of O-TBDMS-steroid in THF
(20 mL/mmol) at 0 ꢂC was slowly added (n-Bu)4NF3$H2O (6 mmol/
mmol). Then, the solution was stirred at room temperature and the
progress of the reaction was followed by TLC analysis. The reaction
mixture was quenched with water and diluted with Et2O. The or-
ganic extract was dried over MgSO4, filtered, and concentrated
under reduced pressure. The crude product was flash chromato-
graphed on silica gel (petroleum ether/AcOEt 60:40).
(75 MHz, CDCl3):
d
¼216.6 (s), 213.7 (s), 157.9 (s), 138.2 (s), 130.5
(d), 130.3 (s), 111.9 (d), 111.5 (d), 80.3 (s), 75.0 (d), 59.6 (d), 55.4
(d), 55.1 (q), 43.2 (d), 42.5 (t), 38.5 (d), 37.4 (d), 31.1 (q), 29.4 (t),
28.6 (t), 28.4 (t), 27.6 (t), 19.4 (q) ppm. C23H30O5 (386.5): C 71.48,
H 7.82; found C 71.36, H 7.92.
4.8.1. (8
b
,9
a,14
a)-13a-Hydroxy-11b-(2(S)-hydroxypropanoyl)-2-
methoxy-17
a-vinylgona-1,3,5(10)-triene (13)
4.10. 3-[(S)-(2-tert-Butyldimethylsilyloxy)-2-phenylacetyl]-
From 5a: 42% yield after 20 h of stirring. White crystals, mp
6,9-divinyl-1-oxa-spiro[4,4]nonan-2-one (17)
20
154 ꢂC, [
d
a
]
D
ꢁ2.6 (c 0.11, CH2Cl2). 1H NMR (300 MHz, CDCl3):
¼6.94 (d, J¼9.0 Hz, 1H), 6.60 (br s, 1H), 6.58 (br d, J¼9.0 Hz, 1H),
The methodology is similar to that described for the preparation
of 2, but O-TBDMS methyl (þ)-(S)-mandelate (12.0 g, 43 mmol) is
used instead of O-TBDMS methyl (þ)-(S)-lactate to give 17 (16.2 g,
36.7 mmol, 85%) as a pink oil. 13C NMR (75 MHz, CDCl3) major
5.82 (dd, J¼17.5, 10.4, 7.8 Hz, 1H), 5.20 (dd, J¼10.3, 1.5 Hz, 1H), 5.09
(dd, J¼17.3, 0.9 Hz), 4.11 (q, J¼7.1 Hz,1H), 3.86 (q, J¼7.4 Hz,1H), 3.70
(s, 3H), 3.28 (OH), 3.08 (dd, J¼11.0, 7.4 Hz, 1H), 2.58–2.84 (m, 2H),
2.35 (dt, J¼11.2, 7.3 Hz,1H),1.96–2.20 (m, 4H),1.83 (1⁄2 AB, d, J¼13.1,
7.9 Hz, 1H), 1.73–1.82 (m, 1H), 1.48–1.70 (m, 2H), 1.36 (d, J¼7.1 Hz,
isomer:
d
¼201.7 (s), 172.0 (s), 138.4 (s), 137.5 (d), 135.8 (d), 128.9 (d),
128.6 (d), 127.3 (d), 118.9 (t), 117.7 (t), 96.4 (s), 80.4 (d), 53.3 (d), 53.1
(d), 52.5 (d), 49.3 (d), 29.8 (t), 28.7 (t), 28.4 (t), 25.8 (q),18.4 (s), ꢁ4.7
(q), ꢁ4.8 (q) ppm.
3H), 1.08–1.30 (m, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼216.3 (s),
157.9 (s), 138.6 (d), 137.1 (s), 130.5 (d), 130.4 (s), 118.3 (t), 112.0 (d),
111.2 (d), 80.4 (s), 75.2 (d), 55.8 (d), 55.4 (d), 54.1 (q), 42.8 (d), 42.3
(d), 38.8 (d), 37.4 (t), 29.4 (t), 29.4 (t), 29.2 (t), 28.7 (t), 19.1 (q) ppm.
C23H30O4 (370.5): C 74.56, H 8.16; found C 74.68, H 8.23.
4.11. 3-[(S)-(2-tert-Butyldimethylsilyloxy)-2-phenylacetyl]-3-
[5-methoxybenzocyclobuten-1-yl]-6,9-divinyl-1-oxa-
spiro[4,4]nonan-2-one (18)
4.8.2. (8
1,3,5(10)-triene (14)
From 5a: 7% yield after 20 h of stirring.8a
b,9a,14a)-11a,13a-(g-lactone)-2-methoxy-17a-vinylgona-
In a 250 mL two-neck flask equipped with a magnetic stirring
bar and a pressure-equalized addition funnel was added potassium
tert-butylate (4.04 g, 36 mmol) and KI (10 g, 60 mmol) in
anhydrous DMSO (90 mL). A solution of 17 (13.2 g, 30 mmol) in
4.8.3. (8
methoxy-17
From 6b: 52% yield after 60 h of stirring. White crystals, mp 159 ꢂC.
1H NMR (300 MHz, CDCl3):
¼6.68 (d, J¼8.1 Hz, 1H), 6.57 (br s, 1H),
b
,9b
,14
a)-13a-Hydroxy-11a-(2(S)-hydroxypropanoyl)-3-
a-vinylgona-1,3,5(10)-triene (15)
anhydrous DMSO (60 mL) and then a solution of 1-iodo-5-
methoxybenzocyclobutene (15.6 g, 60 mmol) in anhydrous DMSO
(60 mL) were added. The content was stirred for 3 days at room
temperature. The mixture was washed with water and the aqueous
phases extracted with Et2O, the organic layers were washed with
brine and dried over MgSO4, filtered, and concentrated under re-
duced pressure. The crude product was flash chromatographed on
silica gel (PE/Et2O 90:10) to give 18 (white solid, 8.6 g, 15 mmol,
d
6.55 (dd, J¼8.1, 2.7 Hz,1H), 5.80 (ddd, J¼17.1,10.2, 9.1 Hz,1H), 5.16 (dd,
J¼10.2, 1.7 Hz), 5.08 (ddd, 17.1, 1.7, 0.8 Hz, 1H), 3.71 (s, 3H), 3.47 (q,
J¼7.16 Hz), 3.31 (1⁄2 AB, dd, J¼11.0, 8.3, 2.9 Hz, 1H), 3.18 (1⁄2 AB, d,
J¼11.0, 4.4 Hz, 1H), 2.85 (1⁄2 AB, dd,J¼17.2,6.4, 2.7 Hz,1H), 2.70(1⁄2 AB,
dd, J¼17.2,11.0, 6.5 Hz,1H), 2.28–2.44 (m, 2H),1.82–2.04 (m, 4H),1.96
(d, J¼12.1 Hz,1H),1.92(d,J¼12.1 Hz,1H),1.58–1.68(m, 3H),1.48(brdd,
J¼13.9, 1.7 Hz, 1H), 1.22 (d, J¼7.2 Hz, 3H) ppm. 13C NMR (75 MHz,
50%). Major isomer, mp 132 ꢂC. 1H NMR (300 MHz, CDCl3):
d¼7.48–
7.52 (m, 2H), 7.26–7.32 (m, 3H), 6.97 (d, J¼8.1 Hz, 1H), 6.81 (dd,
J¼8.0, 2.2 Hz, 1H), 6.65 (d, J¼2.0 Hz, 1H), 6.35 (s, 1H), 4.99–5.16 (m,
2H), 4.50–4.68 (m, 3H), 4.24 (dd, J¼5.0, 2.2 Hz, 1H), 4.15 (br 1⁄2 AB,
J¼16.7 Hz, 1H), 4.01 (dd, J¼9.0, 3.0 Hz, 1H), 3.74 (s, 3H), 3.70 (d,
J¼5.4 Hz, 1H), 3.02 (1⁄2 AB, d, J¼14.6, 5.2 Hz, 1H), 2.61 (1⁄2 AB, d,
J¼14.4, 1.9 Hz, 1H), 2.38 (1⁄2 AB, J¼14.4 Hz, 1H), 2.23 (td, J¼8.6,
3.7 Hz,1H),1.91–2.04 (m, 2H),1.85 (1⁄2 AB, J¼14.4 Hz,1H),1.60–1.72
(m, 2H), 1.45–1.56 (m, 1H), 1.30–1.42 (m, 1H), 0.83 (s, 9H), 0.07 (s,
CDCl3):
d
¼217. 8 (s), 158.2 (s), 139.0 (d), 137.9 (s), 130.5 (d), 129.6 (s),
117.9 (t),114.2 (d),111.6 (d), 78.5 (s), 74.5 (d), 55.2 (q), 54.4 (d), 48.6 (d),
44.7(d), 39.4(d), 38.4(t), 36.1 (d), 29.6 (t), 27.4(t), 26.5 (t), 25.6(t),19.0
(q) ppm. C23H30O4 (370.5): C 74.56, H 8.16; found C 74.38, H 8.27.
4.9. Wacker-type oxidation of 13
To a solution of Pd(OAc)2 (18 mg, 0.08 mmol) and benzoquinone
(79 mg, 0.73 mmol) in 8.1 mL of acetonitrile were successively
added water (1.1 mL) and 70% HClO4 (0.24 mL). After 1 h of stirring,
13 (300 mg, 0.81 mmol) was added and the mixturewas stirreduntil
the disappearance of 13 (the progress of the reaction was followed
by TLC analysis). The reaction mixture was diluted with Et2O and
a 30% soda solution was slowly added until neutrality. The aqueous
layer was extracted with Et2O and the organic extract was dried over
MgSO4, filtered, and concentrated under reduced pressure. The
crude product was flash chromatographed on silica gel (petroleum
ether/AcOEt 50:50) to give 16 (179 mg, 0.46 mmol, 58%).
3H), ꢁ0.18 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
¼200.1 (s),175.0
d
(s), 160.0 (s), 143.4 (s), 137.9 (s), 137.2 (d), 135.2 (s), 133.5 (d), 129.0
(d)(2C), 128.4 (d), 128.3 (d)(2C), 124.4 (d), 119.0 (t), 117.3 (t), 116.4
(d), 107.9 (d), 94.7 (s), 73.0 (d), 63.8 (s), 55.7 (q), 53.0 (d), 52.5 (d),
46.1 (d), 31.6 (t), 27.7 (t), 27.4 (t), 26.8 (t), 25.8 (q)(3C), 18.2 (s), ꢁ4.3
(q), ꢁ4.8 (q) ppm.
4.11.1. Thermolysis of 18
From 18 (2.86 g, 5 mmol): 19 (138 mg, 0.24 mmol, 4.2%) and an
inseparable mixture of 20þ21 (1.5 g, 0.21 mmol, 52.4%), after flash
chromatography (EP/AcOEt 98:2).
4.9.1. (8
b
,9
a
,14
a
)-17
a
-Acetyl-13
a
-hydroxy-11
b
-(2(S)-
4.11.1.1. (8
nylacetyl]-11
triene (19). Mp 75 ꢂC. 1H NMR (500 MHz, CDCl3):
J¼7.95 Hz, 1H), 7.27–7.32 (m, 3H), 6.98 (d, J¼8.3 Hz, 1H), 6.65 (dd,
b
,9
a
a
,14
a
b
)-11
g
b
-[2(S)-2-(tert-Butyldimethylsilyloxy)-2-phe-
-vinylgona-1,3,5(10)-
¼7.44 (d,
hydroxypropanoyl)-2-methoxygona-1,3,5(10)-triene (16)
White crystals, mp 45–48 ꢂC, [
NMR (500 MHz, CDCl3):
,13
-( -lactone)-2-methoxy-17
b
20
a
]
þ104 (c 0.2, CH2Cl2). 1H
d
D
d
¼6.96 (d, J¼8.3 Hz, 1H), 6.64 (br d,

D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
189
J¼8.3, 2.2 Hz,1H), 6.34 (d, J¼1.6 Hz,1H), 5.43 (dt, J¼17.0, 9.7 Hz,1H),
4.15. 3-[5-Methoxybenzocyclobuten-1-yl]-6,9-divinyl-1-oxa-
spiro[4,4]nonan-2-one (24)
5.05 (d, J¼16.9 Hz, 1H), 4.98 (dd, J¼10.1, 0.75 Hz, 1H), 3.99 (d,
J¼5.52 Hz, 1H), 3.58 (s, 3H), 2.98 (dd, J¼12.1, 1.0 Hz, 1H), 2.83 (td,
J¼8.7, 4.3 Hz, 1H), 2.59–2.71 (m, 2H), 2.15–2.22 (m, 1H), 1.94 (1⁄2 AB,
J¼12.1 Hz, 1H), 1.83–1.90 (m, 1H), 1.39–1.64 (m, 3H), 0.82–0.94 (m,
2H), 0.78 (9H, s), 0.04 (3H, s), ꢁ0.30 (3H, s) ppm. 13C NMR (75 MHz,
The deprotection by HF–pyridine of 18b led to 24 in 80% yield.
Compound 24: white wax. 1H NMR (300 MHz, CDCl3):
¼6.97 (d,
d
J¼2.0 Hz,1H), 6.87 (d, J¼8.1 Hz,1H), 6.77 (dd, J¼8.1, 2.0 Hz,1H), 5.92
(ddd, J¼17.4, 10.2, 8.5 Hz, 1H), 5.56–5.46 (m, 2H), 5.20 (dd, J¼10.2,
1.9 Hz, 1H), 5.04–5.14 (m, 4H), 3.78 (s, 3H), 3.52–3.55 (m, 1H), 3.01
(1⁄2 AB, d, J¼14.4, 2.6 Hz, 1H), 2.91 (1⁄2 AB, d, J¼14.5, 5.2 Hz, 1H),
2.58–2.67 (m, 2H), 2.34–2.46 (m, 3H), 2.04–2.15 (m, 2H), 1.88 (d,
J¼13.9 Hz, 1H), 1.64–1.77 (m, 3H), 1.48–1.65 (m, 2H), 1.15–1.26 (m,
CDCl3):
d
¼204.1 (s), 173.7 (s), 157.8 (s), 138.7 (s), 137.6 (s), 135.3 (d),
130.9 (s), 129.6 (d), 128.6 (d), 128.4 (d)(2C), 128.2 (t), 128.1 (d)(2C),
116.8 (d), 114.5 (d), 111.7 (d), 96.1 (s), 78.4 (d), 64.8 (s), 55.2 (q), 49.1
(d), 45.7 (d), 40.7 (t), 36.6 (t), 36.4 (t), 29.8 (t), 27.1 (t), 25.9 (q)(3C),
25.7 (q), 18.1 (s), ꢁ4.3 (q), ꢁ4.9 (q) ppm. C35H44O5Si (572.8): C
73.39, H 7.74; found C 73.28, H 7.82.
3H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼178.3 (s), 159.6 (s), 145.5 (s),
139.1 (d), 138.3 (d), 135.5 (s), 135.1 (s), 128.5 (d), 126.2 (d), 123.4 (d),
123.4 (d), 117.9 (t), 117.4 (t), 115.8 (d), 109.6 (d), 96.5 (s), 86.4 (d),
56.7 (s), 55.7 (d), 53.1 (d), 51.7 (d), 42.6 (d), 33.3 (t), 32.3 (t), 28.1 (t),
27.9 (t) ppm. C21H24O3 (324.4): C 77.75, H 7.46; found C 77.86, H
7.53.
´
4.11.1.2. (8
nylacetyl]-11
triene (20). In mixture with 21. 1H NMR (300 MHz, CDCl3)
(partial):
a
,9
b
,14
b
)-11
b-[2(S)-2-(tert-Butyldimethylsilyloxy)-2-phe-
a
,13
a
-(g-lactone)-2-methoxy-17
b
-vinylgona-1,3,5(10)-
d
¼6.99 (d, J¼8.2 Hz, 1H), 6.61 (dd, J¼2.3 Hz, 1H), 6.32
(d, J¼2.3 Hz, 1H), 5.27 (s, 1H), 5.05 (d, J¼11.2 Hz, 1H), 5.00 (d,
J¼18.0 Hz, 1H), 3.53 (s, 3H), 3.32 (d, J¼10.7 Hz, 1H), 2.20 (1⁄2 AB,
J¼12.4 Hz, 1H), 0.76 (9H, s), 0.09 (3H, s), ꢁ0.23 (3H, s) ppm. 13C
4.16. Wacker-type oxidation of 22
NMR (75 MHz, CDCl3):
d
¼204.7 (s), 176.2 (s), 157.6 (s), 141.2 (s),
The methodology is similar to that described for the oxidation
of 13.
138.5 (s), 135.4 (d), 129.5 (d), 128.9 (d), 128.7 (d), 128.3 (d), 116.8
(t), 112.7 (d), 110.3 (d), 92.6 (s), 80.9 (d), 59.9 (s), 55.0 (q), 52.8
(d), 51.1 (d), 46.1 (d), 42.9 (d), 37.3 (t), 31.6 (t), 30.2 (t), 27.5 (t),
27.2 (t), 25.9 (q)(3C), 18.2 (s), ꢁ4.7 (q), ꢁ4.8 (q) ppm.
4.17. (8
phenylacetyl]-11
1,3,5(10)-triene (25)
a
,9
b
,14
b
)-17
b-Acetyl-11b-[2(S)-2-hydroxy-2-
a
,13
a
-(g-lactone)-2-methoxygona-
4.12. Deprotection of alcohols 21D22 by HF–pyridine
20
Yield 57.4%, mp 110 ꢂC, [
(300 MHz, CDCl3):
a]
þ115 (c0.10, CH2Cl2). 1H NMR
D
The methodology is similar to that described for the depro-
tection of 5–8.
d
¼7.27–7.38 (m, 5H), 7.00 (d, J¼8.3 Hz, 1H),
6.70 (d, J¼2.5 Hz, 1H), 6.66 (br s, 1H), 5.21 (s, 1H), 3.72 (s, 3H),
3.60 (d, J¼10.3 Hz, 1H), 2.65–2.70 (m, 2H), 2.50 (dd, J¼11.5,
7.4 Hz, 1H), 2.30 (1⁄2 AB, J¼14.7 Hz, 1H), 2.18–2.25 (m, 2H), 2.03
(s, 3H), 1.89 (1⁄2 AB, J¼15.0 Hz, 1H), 1.84–2.00 (m, 2H), 1.16 (1⁄2
AB, J¼15.0 Hz, 1H), 1.15–1.30 (m, 2H) ppm. 13C NMR (75 MHz,
4.13. (8
11 ,13 -(
triene (22)
a
,9
b
,14
b
)-11
b
-[2(S)-2-Hydroxy-2-phenylacetyl]-
a
a
g-lactone)-2-methoxy-17b
-vinylgona-1,3,5(10)-
CDCl3):
d
¼210.4 (s), 208.5 (s), 180.2 (s), 158.3 (s), 135.3 (s), 132.6
White crystals in 54% yield, mp 104 ꢂC, [
1H NMR (300 MHz, CDCl3):
a
]
20 163 (c 0.17, CH2Cl2).
(s), 131.4 (s), 131.2 (d), 129.3 (d), 129.2 (d)(2C), 125.2 (d)(2C),
113.4 (d), 110.6 (d), 85.7 (d), 79.7 (s), 61.7 (d), 55.3 (q), 55.1 (d),
52.2 (s), 46.2 (d), 41.2 (t), 38.1 (d), 30.8 (q), 29.7 (t), 29.5 (t), 28.1
(t), 27.0 (t) ppm. C29H30O6 (474.5): C 73.40, H 6.37; found C
73.49, H 6.41.
D
d
¼7.25–7.42 (m, 5H), 7.01 (d, J¼8.0 Hz,
1H), 6.69 (d, J¼8.0 Hz, 1H), 6.68 (s, 1H), 5.85 (ddd, J¼17.5, 10.4,
7.7 Hz, 1H), 5.20 (s, 1H), 5.01 (br dd, J¼10.4, 1.6 Hz, 1H), 4.87 (br d,
J¼17.5 Hz, 1H), 4.87 (br d, J¼17.5 Hz, 1H), 3.72 (s, 3H), 3.66 (br d,
J¼10.5 Hz,1H), 2.67 (s, OH, 1H),1.97 (1⁄2 AB, J¼14.8 Hz,1H), 1.76 (1⁄2
AB, J¼14.7 Hz, 1H), 1.60–2.20 (m, 7H), 1.17 (1⁄2 AB, J¼14.9 Hz, 1H),
4.18. 3-Carboxy-6,9-divinyl-1-oxa-spiro[4,4]nonan-2-one
(1,2:5,6-di-O-isopropylidene-a-D-glucofuranos-3-yl) ester (27)
1.12–1.32 (m, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d¼208.3 (s),
180.8 (s), 158.3 (s), 137.5 (d), 135.4 (s), 132.6 (s), 131.5 (d), 131.2 (s),
129.2 (s), 129.1 (d)(2C), 125.2 (d)(2C), 116.3 (t), 113.3 (d), 110.5 (d),
85.8 (d), 79.1 (s), 56.2 (d), 56.1 (d), 55.3 (q), 52.2 (s), 46.6 (d), 41.2 (t),
38.3 (d), 30.3 (d), 29.5 (t), 28.0 (t) ppm. C29H30O5 (458.5): C 75.96, H
6.59; found C 76.03, H 6.51.
The methodology is similar to that described for the preparation
of 2, but DAG carbonate (26) (20.5 g, 43 mmol) is used instead of O-
TBDMS methyl (þ)-(S)-lactate and the reaction mixture was stirred
at ꢁ20 ꢂC for 24 h to give 27 (14.6 g, 30.5 mmol, 71%) as a white
wax. 13C NMR (75 MHz, CDCl3) major isomer:
d
¼170.3 (s), 166.2 (s),
4.14. (8
11 ,13 -(
triene (23)
b
,9
a
,14
a
)-11
b
-[2(S)-2-Hydroxy-2-phenylacetyl]-
137.2 (d), 134.8 (d), 118.8 (t), 117.4 (t), 112.1 (s), 109.1 (s), 104.9 (d),
95.4 (s), 82.9 (d), 79.4 (d), 77.1 (d), 71.9 (d), 67.1 (t), 52.8 (d), 52.1 (d),
47.4 (d), 30.6 (t), 28.8 (t), 28.4 (t), 26.7 (q), 26.5 (q), 26.0 (q), 24.9
(q) ppm.
a
a
g-lactone)-2-methoxy-17
a-vinylgona-1,3,5(10)-
20
White crystals in 21% yield, mp 166 ꢂC, [
1H NMR (300 MHz, CDCl3):
a
]
þ69 (c 0.2, CH2Cl2).
D
d
¼7.21–7.35 (m, 5H), 6.87 (d, J¼8.5 Hz,
4.19. 3-Carboxy-3-(5-methoxybenzocyclobuten-1-yl)-6,9-
divinyl-1-oxa-spiro[4,4]nonan-2-one (1,2:5,6-di-O-
isopropylidene-a-D-glucofuranos-3-yl) ester (28a)
1H), 6.41 (dd, J¼8.4, 2.2 Hz, 1H), 6.36 (d, J¼2.1 Hz, 1H), 5.70 (s, 1H),
5.93 (m, 1H), 4.94–5.14 (m, 4H), 3.65 (d, J¼9.3 Hz, 1H), 2.63 (tt,
J¼12.4, 2.3 Hz, 2H), 3.39 (s, 3H), 2.77 (ddd, J¼17, 5.4, 2.1 Hz, 1H),
2.29 (1⁄2 AB, J¼13.6 Hz, 1H), 2.16–2.19 (m, 2H), 1.97 (1⁄2 AB,
J¼13.5 Hz, 1H), 1.95–2.00 (m, 1H), 1.76–1.90 (m, 3H), 1.14–1.27 (m,
In a 250 mL two-neck flask equipped with a magnetic stirring
bar and a pressure-equalized addition funnel was added 27
(2.5 g, 5.2 mmol) in anhydrous acetone (31 mL), KI (1.12 g,
6.8 mmol), and cesium carbonate (2.2 g, 6.8 mmol). A solution of
1-iodo-5-methoxybenzocyclobutene (1.76 g, 6.8 mmol) in anhy-
drous acetone (34 mL) was added. The content was stirred at
reflux for 2 days. The mixture was cooled, filtered (washing with
Et2O), and concentrated under reduced pressure. The crude
2H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼208.3 (s), 179.7 (s), 157.9 (s),
137.6 (d), 135.7 (s), 131.0 (s), 130.8 (d), 130.6 (s), 128.8 (d), 128.5
(d)(2C), 126.5 (d)(2C), 116.7 (t), 112.4 (d), 111.5 (d), 83.7 (d), 79.9 (s),
56.7 (d), 56.4 (d), 54.8 (q), 53.6 (s), 44.4 (d), 42.5 (t), 38.8 (d), 30.5
(t), 30.3 (t), 29.5 (t), 28.2 (t) ppm. C29H30O5 (458.5): C 75.96, H 6.59;
found C 75.86, H 6.63.

190
D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
product was flash chromatographed on silica gel (PE/Et2O 80:20)
4.20.2. Thermolysis of 28b
to give 28a (white powder, 2.4 g, 3.9 mmol, 76%). 13C NMR
From 28b (3.2 g, 5.4 mmol): 29b (1.58 g, 2.59 mmol, 49.4%), and
30b (620 mg, 1.04 mmol, 20%) after flash chromatography (EP/
AcOEt 70:30).
(75 MHz, CDCl3) major isomer:
d
¼172.9 (s), 168.4 (s), 159.9 (s),
143.4 (s), 137.1 (d), 135.0 (d), 124.2 (d), 118.9 (t), 117.6 (t), 116.3 (d),
112.4 (s), 109.5 (s), 108.0 (d), 105.3 (d), 94.0 (s), 83.2 (d), 80.3 (d),
77.6 (d), 72.4 (d), 67.9 (t), 57.7 (s), 55.7 (d), 53.2 (d), 52.8 (d), 46.1
(d), 32.4 (t), 30.1 (t), 28.0 (t), 27.8 (t), 27.0 (q), 26.8 (q), 26.3 (q),
25.4 (q) ppm.
4.20.2.1. (8
a
,9
b
,14
b
)-11
a
-Carboxy-11
b
,13
b
-(
g
-lactone)-3-methoxy-
17
b
-vinylgona-1,3,5(10)-triene (1,2:5,6-di-O-isopropylidene-a-D-glu-
20
cofuranos-3-yl) ester (29b). White powder, mp¼95 ꢂC, [
a
]
þ11.6
D
(c 0.19, CH2Cl2). 1H NMR (500 MHz, CDCl3):
d
¼6.86 (d, J¼8.5 Hz,1H),
4.20. 3-Carboxy-3-(4-methoxybenzocyclobuten-1-yl)-6,9-
divinyl-1-oxa-spiro[4,4]nonan-2-one (1,2:5,6-di-O-
isopropylidene-a-D-glucofuranos-3-yl) ester (28b)
6.69 (d, J¼2.5 Hz, 1H), 6.62 (dd, J¼8.5, 2.6 Hz, 1H), 5.87 (d, J¼3.5 Hz,
1H), 5.85 (ddd, J¼17.7, 9.5, 8.2 Hz, 1H), 5.77 (d, J¼3.4 Hz, 1H), 5.20
(d, J¼3.0 Hz, 1H), 5.08–5.152 (m, 2H), 4.29 (d, J¼3.2 Hz, 1H), 4.13
(dd, J¼6.6, 3.0 Hz, 1H), 3.83 (dd, J¼8.3, 4.7 Hz, 1H), 3.71 (s, 3H), 3.54
(q, J¼5.9 Hz, 1H), 3.47 (dd, J¼8.1, 6.6 Hz, 1H), 2.99 (d, J¼11.0 Hz, 1H),
2.70–2.78 (m, 2H), 2.65 (1⁄2 AB, J¼12.2 Hz, 1H), 2.45 (dt, J¼10.8,
7.3 Hz, 1H), 2.26 (1⁄2 AB, J¼12.3 Hz, 1H), 2.01–2.07 (m, 2H), 1.84–
1.94 (m, 4H), 1.66 (qd, J¼12.2, 6.3 Hz, 1H), 1.45 (s, 3H), 1.30 (s, 3H),
The same procedure with 1-iodo-4-methoxybenzocyclobutene
led to 28b (white powder, 2.66 g, 4.35 mmol, 84%). 13C NMR
(75 MHz, CDCl3) major isomer:
d
¼172.8 (s), 168.5 (s), 160.8 (s),
144.6 (s), 137.3 (d), 135.2 (d), 134.3 (d), 124.0 (d), 118.9 (t), 117.5 (t),
114.1 (d), 112.4 (s), 109.5 (s), 108.3 (d), 105.3 (d), 94.0 (s), 83.2 (d),
80.3 (d), 77.6 (d), 72.4 (d), 67.8 (t), 57.8 (s), 55.6 (d), 53.1 (d), 52.8
(d), 46.1 (d), 32.8 (t), 30.1 (t), 28.0 (t), 27.8 (t), 27.0 (q), 26.8 (q),
26.2 (q), 25.4 (q) ppm.
1.23 (s, 3H), 0.99 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d¼175.2
(s), 169.3 (s), 158.1 (s), 139.2 (s), 135.0 (d), 117.4 (t), 114.7 (d), 112.3
(s), 111.1 (d), 109.0 (s), 105.2 (d), 93.2 (s), 82.4 (d), 79.5 (d), 77.7 (d),
72.3 (d), 66.3 (t), 60.4 (s), 55.5 (q), 55.2 (s), 53.2 (d), 51.0 (d), 43.4 (d),
42.3 (d), 35.7 (t), 31.8 (t), 30.5 (t), 28.0 (t), 26.8 (q), 26.7 (t), 27.0 (q),
26.2 (q), 26.1 (t), 24.6 (q) ppm. C34H42O10 (610.7): C 66.87, H 6.93;
found C 66.91, H 6.88.
4.20.1. Thermolysis of 28a
From 28a (2.4 g, 3.9 mmol): 29a (984 mg, 1.61 mmol, 41.3%), 30a
(509 mg, 0.83 mmol, 21.2%), but in mixture with remaining 28a,
and 31 (312 mg, 0.51 mmol, 13.4%) after flash chromatography (EP/
AcOEt 80:20).
4.20.2.2. (8
17
b
,9
a
,14
a
)-11
b
-Carboxy-11
a
,13
a
-(
g
-lactone)-3-methoxy-
-glu-
þ12 (c
a
-vinylgona-1,3,5(10)-triene (1,2:5,6-di-O-isopropylidene-a-D
cofuranos-3-yl) ester (30b). White powder, mp¼93 ꢂC, [
20
a]
D
4.20.1.1. (8
17
a
,9
b
,14
b
)-11
a
-Carboxy-11
b
,13
b
-(
g
-lactone)-2-methoxy-
-glu-
þ34.4
0.1, CH2Cl2). 1H NMR (500 MHz, CDCl3):
d
¼7.13 (d, J¼8.8 Hz, 1H),
b
-vinylgona-1,3,5(10)-triene (1,2:5,6-di-O-isopropylidene-
cofuranos-3-yl) ester (29a). White powder, mp¼90 ꢂC, [
a
-
D
6.62 (dd, J¼8.8, 2.6 Hz, 1H), 6.51 (d, J¼2.7 Hz, 1H), 5.87 (d,
J¼3.7 Hz, 1H), 5.77–5.86 (m, 1H), 5.57 (d, J¼2.9 Hz, 1H), 5.05–5.13
(m, 3H), 4.47 (d, J¼3.7 Hz, 1H), 4.34–4.41 (m, 2H), 4.27 (br d,
J¼7.4 Hz, 1H), 4.24 (dd, J¼8.3, 3.05 Hz, 1H), 4.08 (1⁄2 AB, d J¼8.6,
6.1 Hz, 1H), 3.97 (1⁄2 AB, d J¼8.7, 4.5 Hz, 1H), 3.70 (s, 3H), 2.79
(quint, J¼8.04 Hz, 2H), 2.54 (1⁄2 AB, J¼11.6 Hz, 1H), 2.40–2.46 (m,
2H), 2.37 (1⁄2 AB, J¼11.7 Hz, 1H), 2.09–2.24 (m, 2H), 1.84–1.90 (m,
3H), 1.64 (qd, J¼11.9, 5.3 Hz, 1H), 1.52 (s, 3H), 1.44 (s, 3H), 1.37 (s,
20
a]
D
(c 0.16, CH2Cl2). 1H NMR (500 MHz, CDCl3):
d
¼7.01 (d, J¼8.2 Hz,
1H), 6.63 (dd, J¼8.2, 2.4 Hz, 1H), 6.50 (d, J¼2.1 Hz, 1H), 5.85
(ddd, J¼17.7, 9.6, 8.1 Hz, 1H), 5.79 (d, J¼2.9 Hz, 1H), 5.21 (d,
J¼2.9 Hz, 1H), 5.12 (d, J¼15.8 Hz, 1H), 5.11 (d, J¼10.8 Hz, 1H),
4.38 (d, J¼3.3 Hz, 1H), 4.10 (dd, J¼7.1, 2.9 Hz, 1H), 3.85 (dd, J¼8.3,
4.1 Hz, 1H), 3.70 (s, 3H), 3.48–3.55 (m, 2H), 3.04 (1⁄2 AB,
J¼11.0 Hz, 1H), 2.66–2.80 (m, 3H), 2.46 (dt, J¼11.2, 7.6 Hz, 1H),
2.26 (1⁄2 AB, J¼12.2 Hz, 1H), 2.05 (quint, J¼6.02 Hz, 1H), 1.82–
1.92 (m, 3H), 1.66 (qd, J¼12.3, 5.5 Hz, 1H), 1.46 (s, 3H), 1.30 (s,
3H), 1.25 (s, 3H), 0.99 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
3H), 1.30 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼171.4 (s), 170.1
(s), 157.7 (s), 137.9 (s), 135.3 (d), 131.8 (d), 124.7 (s), 117.0 (t), 113.4
(d), 112.5 (d), 112.1 (s), 109.4 (s), 105.2 (d), 91.3 (s), 83.4 (d), 80.4
(d), 77.3 (d), 72.2 (d), 67.4 (t), 57.1 (s), 55.1 (q), 51.6 (d), 45.8 (d),
41.1 (t), 39.5 (d), 35.1 (d), 31.6 (t), 30.3 (t), 27.1 (q), 26.8 (q), 26.4
(q), 25.4 (q), 25.0 (t), 24.7 (t) ppm. C34H42O10 (610.7): C 66.87, H
6.93; found C 66.85, H 6.87.
d
¼175.1 (s), 169.4 (s), 158.0 (s), 134.9 (d), 129.5 (d), 129.3 (s),
117.4 (t), 112.3 (s), 112.3 (d), 109.1 (s), 105.2 (d), 93.2 (s), 82.3 (d),
79.4 (d), 77.6 (d), 72.0 (d), 66.4 (t), 55.5 (s), 55.1 (q), 53.2 (d),
50.9 (d), 43.2 (d), 42.9 (d), 35.5 (t), 31.8 (t), 30.7 (t), 26.75 (q),
26.72 (q), 26.5 (t), 26.4 (t), 26.2 (q), 24.3 (q) ppm. C34H42O10
(610.7): C 66.87, H 6.93; found C 66.95, H 7.03.
4.21. Partial deprotection of steroids 29 and 30
Steroid (1 mmol) in 70% acetic acid (20 mL/mmol) was stirred at
room temperature for 20 h. After concentration under reduced
pressure, the crude product was flash chromatographed on silica
gel (EP/AcOEt 50:50).
4.20.1.2. (8
a
,9
a
,14
b
)-11
a
-Carboxy-11
b
,13
b
-(
g
-lactone)-2-methoxy-
17
b
-vinylgona-1,3,5(10)-triene (1,2:5,6-di-O-isopropylidene-a-D-glu-
20
cofuranos-3-yl) ester (31). White powder, mp¼88 ꢂC, [
a
]
50 (c
D
0.105, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
¼6.9 (d, J¼8.4 Hz,
1H), 6.76 (d, J¼2.3 Hz, 1H), 6.62 (dd, J¼8.4, 2.5 Hz, 1H), 5.86 (d,
J¼3.6 Hz, 1H), 5.77–5.85 (m, 1H), 5.47 (d, J¼2.7 Hz, 1H), 5.03–5.08
(m, 2H), 4.49 (d, J¼3.6 Hz, 1H), 4.23 (td, J¼8.0, 2.7 Hz, 1H), 4.05
(dd, J¼8.5, 5.8 Hz, 1H), 3.94 (dd, J¼8.5, 4.5 Hz, 1H), 3.70 (s, 3H),
2.64–2.78 (m, 2H), 2.54 (1⁄2 AB, J¼11.5 Hz, 1H), 2.39–2.55 (m,
2H), 2.38 (1⁄2 AB, J¼11.5 Hz, 1H), 2.10–2.16 (m, 3H), 1.83–1.92 (m,
4H), 1.51 (s, 3H), 1.40 (s, 3H,), 1.30 (s, 3H), 1.29 (s, 3H) ppm. 13C
4.22. (8
methoxy-17
isopropylidene-
a
,9
b
,14
-vinylgona-1,3,5(10)-triene (1,2-O-
-glucofuranos-3-yl) ester (32)
b)-11a-Carboxy-11b,13b-(g-lactone)-2-
b
a-D
From 29a: 54% yield. White powder, mp¼99 ꢂC. 1H NMR
(300 MHz, CDCl3):
d
¼7.11 (d, J¼8.2 Hz, 1H), 6.71 (dd, J¼8.2, 2.0 Hz,
1H), 6.55 (d, J¼1.5 Hz, 1H), 5.88 (d, J¼3.6 Hz, 1H), 5.80–5.92 (m,
1H), 5.34 (d, J¼2.4 Hz, 1H), 5.15 (d, J¼16.5 Hz, 1H), 5.13 (d,
J¼11.0 Hz, 1H), 4.49 (d, J¼3.4 Hz, 1H), 4.12 (dd, J¼7.9, 2.5 Hz, 1H),
3.73 (s, 3H), 3.34–3.52 (m, 4H), 3.05 (d, J¼10.8 Hz, 1H), 3.03–3.06
(m, 1H), 2.78 (1⁄2 AB, J¼12.0 Hz, 1H), 2.69–2.86 (m, 2H), 2.48 (dt,
J¼11.7, 7.3 Hz, 1H), 2.23 (1⁄2 AB, J¼12.1 Hz, 1H), 2.00–2.10 (m, 2H),
1.80–1.96 (m, 4H), 1.68 (dd, J¼12.5, 5.2 Hz, 1H), 1.49–1.65 (m, 3H),
1.45 (s, 3H), 1.26 (s, 3H), 1.15–1.25 (m, 2H), 0.94 (qd, J¼12.0, 5.5 Hz,
NMR (75 MHz, CDCl3):
d
¼171.2 (s), 170.4 (s), 157.2 (s), 135.2 (d),
133.6 (s), 129.8 (d), 128.6 (s), 117.0 (t), 115.4 (d), 113.1 (d), 112.5
(s), 109.4 (s), 105.0 (d), 91.3 (s), 83.2 (d), 80.2 (d), 77.6 (d), 71.9
(d), 67.2 (t), 57.2 (s), 55.1 (q), 51.5 (d), 45.9 (d), 41.2 (t), 40.1 (d),
34.9 (d), 31.5 (t), 30.3 (t), 26.9 (q), 26.7 (q), 26.2 (q), 25.1 (t), 24.9
(q), 23.8 (t) ppm. C34H42O10 (610.7): C 66.87, H 6.93; found C
66.77, H 6.86.

D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
191
1H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼175.0 (s), 169.2 (s), 158.2
4.26. (8
methoxy-17
isopropylidene-
a
,9
a
,14
-vinylgona-1,3,5(10)-triene (1,2-O-
-glucofuranos-3-yl) ester (36)
b)-11a-Carboxy-11b,13b-(g-lactone)-2-
(s), 139.7 (s), 134.8 (d), 133.0 (s), 122.6 (d), 117.1 (t), 115.2 (d), 112.1
(s)(2C), 110.2 (d), 104.9 (d), 93.1 (s), 81.9 (d), 78.6 (d), 77.4 (d), 68.4
(d), 63.9 (t), 55.2 (q), 52.9 (d), 50.6 (d), 42.9 (d), 42.2 (d), 35.5 (t),
31.6 (t), 30.2 (t), 27.9 (t), 26.5 (q), 26.0 (q), 25.8 (t) ppm. C31H38O10
(570.6): C 65.25, H 6.71; found C 65.16, H 6.75.
b
a-D
20
From 31: 49% yield. White powder, mp¼97 ꢂC, [
a
]
74 (c
D
0.53, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
¼6.87 (d, J¼8.5 Hz,
1H), 6.66 (d, J¼2.3 Hz, 1H), 6.59 (dd, J¼8.5, 2.3 Hz, 1H), 5.88 (d,
J¼3.7 Hz, 1H), 5.77 (ddd, J¼17.6, 9.5, 8.3 Hz, 1H), 5.55 (d,
J¼3.2 Hz, 1H), 5.52 (d, J¼3.4 Hz, 1H), 5.06 (d, J¼17.6 Hz, 1H), 5.05
(d, J¼9.5 Hz, 1H), 4.49 (d, J¼3.7 Hz, 1H), 4.32 (d, J¼6.5 Hz, 1H),
3.84–3.92 (m, 1H), 3.76 (dd, J¼11.2, 2.0 Hz, 1H), 3.65 (s, 3H),
3.64 (dd, J¼11.2, 5.1 Hz, 1H), 2.62–2.74 (m, 1H), 2.54 (1⁄2 AB,
J¼11.7 Hz, 1H), 2.38–2.50 (m, 3H), 2.34 (1⁄2 AB, J¼11.7 Hz, 1H),
2.02–2.20 (m, 4H), 1.80–1.90 (m, 3H), 1.65 (qd, J¼11.9, 4.6 Hz,
1H), 1.47 (s, 3H), 1.26 (s, 3H), 1.17 (q, J¼7.1 Hz, 1H) ppm. 13C NMR
4.23. (8
methoxy-17
isopropylidene-
a
,9
b
,14
-vinylgona-1,3,5(10)-triene (5,6-O-
-glucofuranos-3-yl) ester (33)
b)-11a-Carboxy-11b,13b-(g-lactone)-2-
b
a-D
From 29a: 10% yield. White powder, mp¼99 ꢂC. 1H NMR
(300 MHz, CDCl3):
d¼7.05 (d, J¼8.3 Hz, 1H), 6.72 (dd, J¼8.3, 2.0 Hz,
1H), 6.41 (d, J¼1.9 Hz, 1H), 5.67 (d, J¼3.6 Hz, 1H), 5.49 (d, J¼2.8 Hz,
1H), 5.42 (dt, J¼17.4, 9.1 Hz, 1H), 5.08 (d, J¼17.0 Hz, 1H), 5.01 (d,
J¼10.0 Hz, 1H), 4.98–5.09 (m, 2H), 4.59 (d, J¼3.68 Hz, 1H), 4.31 (dd,
J¼9.0, 2.8 Hz, 1H), 4.14 (br d, J¼4.5 Hz, 1H), 3.94–4.02 (m, 1H), 3.84
(br dd, J¼11.2, 2.0 Hz, 1H), 3.70 (s, 3H), 3.61–3.67 (m, 2H), 2.87 (td,
J¼8.5, 4.2 Hz, 1H), 2.80 (1⁄2 AB, J¼12.2 Hz, 1H), 2.66–2.70 (m, 2H),
2.08–2.23 (m, 4H), 1.87 (1⁄2 AB, J¼12.2 Hz, 1H), 1.84–1.90 (m, 1H),
1.71 (dd, J¼13.4, 4.7 Hz, 1H), 1.53–1.60 (m, 2H), 1.49 (s, 3H), 1.27 (s,
(75 MHz, CDCl3):
d
¼173.1 (s), 170.8 (s), 156.8 (s), 134.9 (d), 133.5
(s), 129.9 (d), 128.8 (s), 117.1 (t), 115.4 (d), 112.4 (d), 112.2 (s),
105.0 (d), 92.2 (s), 83.2 (d), 78.8 (d), 78.6 (d), 68.3 (d), 64.5 (t),
57.1 (s), 55.1 (q), 51.1 (d), 45.5 (d), 40.8 (t), 40.0 (d), 34.4 (d),
31.4 (t), 30.1 (t), 26.6 (q), 26.2 (q), 24.8 (t), 23.5 (t) ppm.
C31H38O10 (570.6): C 65.25, H 6.71; found C 65.32, H 6.81.
3H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼174.9, 169.0, 158.1, 136.8,
134.6, 130.7, 130.6, 117.4, 112.9, 112.5, 111.4, 105.3, 97.7, 82.4, 79.3,
78.6, 69.0, 64.9, 60.8, 55.4, 48.9, 44.5, 40.7, 36.3, 36.1, 31.7, 29.5, 27.1,
26.8, 26.1, 25.4, 25.0 ppm.
4.27. (8
methoxy-17
isopropylidene-
a
,9
b
,14
-vinylgona-1,3,5(10)-triene (1,2-O-
-glucofuranos-3-yl) ester (37)
b)-11a-Carboxy-11b,13b-(g-lactone)-3-
b
a-D
4.24. (8
methoxy-17
isopropylidene-
b
,9
a
,14
-vinylgona-1,3,5(10)-triene (1,2-O-
-glucofuranos-3-yl) ester (34)
a)-11b-Carboxy-11a,13a-(g-lactone)-2-
20
a
From 29b: 54% yield. White powder, mp¼103 ꢂC, [
a]
68 (c
D
a-
D
0.11, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
¼6.83 (d, J¼8.4 Hz, 1H),
6.69 (d, J¼2.0 Hz, 1H), 6.61 (dd, J¼8.5, 2.3 Hz, 1H), 5.80 (ddd,
J¼17.1, 10.1, 8.3 Hz, 1H), 5.70 (d, J¼3.3 Hz, 1H), 5.15 (d, J¼2.4 Hz,
1H), 5.07 (br d, J¼18.0 Hz, 1H), 5.06 (br d, J¼9.7 Hz, 1H), 4.16 (br
d, J¼2.3 Hz, 1H), 4.03 (dd, J¼7.2, 1.1 Hz, 1H), 3.67 (s, 3H), 3.31–
3.47 (m, 2H), 3.04–3.10 (m, 1H), 3.0 (d, J¼11.0 Hz, 1H), 2.71–2.82
(m, 2H), 2.61 (1⁄2 AB, J¼12.2 Hz, 1H), 2.42 (dt, J¼11.1, 7.3 Hz, 1H),
2.23 (1⁄2 AB, J¼12.2 Hz, 1H), 2.01 (q, J¼5.6 Hz, 1H), 1.80–1.90 (m,
2H), 1.61 (qd, J¼11.9, 5.3 Hz, 1H), 1.37 (s, 3H), 1.17 (s, 3H), 0.94 (qd,
20
From 30a: 32% yield. White powder, mp¼97 ꢂC, [
a
]
ꢁ107 (c
D
0.2, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
¼7.06 (d, J¼8.3 Hz, 1H),
6.63 (dd, J¼8.3, 2.1 Hz, 1H), 6.43 (d, J¼1.9 Hz, 1H), 5.81 (ddd, J¼17.2,
10.0, 8.2 Hz, 1H), 5.24 (t, J¼1.4 Hz, 1H), 5.11 (br d, J¼17.2 Hz, 1H),
5.09 (br d, J¼10.0 Hz, 1H), 4.93 (d, J¼3.4 Hz, 1H), 4.62 (d, J¼3.5 Hz,
1H), 4.18 (dd, J¼9.0, 2.9 Hz, 2H), 3.74–3.84 (m, 1H), 3.69 (s, 3H),
3.66–3.71 (m, 1H), 3.50 (dd, J¼11.5, 6.6 Hz, 1H), 2.91 (d, J¼11.0 Hz,
1H), 2.78 (1⁄2 AB, J¼11.7 Hz, 1H), 2.65–2.82 (m, 3H), 2.48 (dt, J¼11.8,
7.4 Hz, 1H), 2.22 (1⁄2 AB, J¼12.3 Hz, 1H), 1.92–2.02 (m, 2H), 1.80–
1.94 (m, 4H), 1.63 (qd, J¼12.3, 5.3 Hz, 1H), 1.45–1.60 (m, 2H), 1.41 (s,
J¼11.7, 5.4 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3):
¼175.0 (s),
d
169.2 (s), 158.2 (s), 139.7 (s), 134.8 (d), 133.1 (s), 122.5 (d), 117.2
(t), 115.2 (d), 112.1 (s)(2C), 110.2 (d), 105.0 (d), 93.2 (s), 81.9 (d),
78.6 (d), 77.5 (d), 68.4 (d), 63.9 (t), 55.2 (q), 52.9 (d), 50.6 (d), 43.0
(d), 42.2 (d), 35.5 (t), 31.6 (t), 30.2 (t), 27.9 (t), 26.5 (q), 26.0 (q),
25.8 (t) ppm. C31H38O10 (570.6): C 65.25, H 6.71; found C 65.28, H
6.61.
3H), 1.22 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼177.2 (s), 168.9
(s), 157.2 (s), 143.1 (s), 134.5 (d), 130.0 (d), 129.5 (s), 117.6 (t), 112.1
(s), 109.1 (d), 108.5 (d), 104.9 (d), 94.8 (s), 81.1 (d), 78.9 (d), 78.4 (d),
69.2 (d), 64.4 (t), 56.0 (q), 55.2 (s), 53.3 (d), 50.6 (d), 43.1 (d), 41.9
(d), 34.7 (t), 31.7 (t), 30.8 (t), 26.5 (q), 26.1 (t), 25.8 (t), 25.6 (q) ppm.
C31H38O10 (570.6): C 65.25, H 6.71; found C 65.33, H 6.71.
4.28. (8
methoxy-17
isopropylidene-a-D
a
,9
b
,14
-vinylgona-1,3,5(10)-triene (5,6-O-
-glucofuranos-3-yl) ester (38)
b)-11a-Carboxy-11b,13b-(g-lactone)-3-
4.25. (8
methoxy-17
isopropylidene-
b
,9
a
,14
-vinylgona-1,3,5(10)-triene (5,6-O-
-glucofuranos-3-yl) ester (35)
a
)-11
b
-Carboxy-11
a
,13
a
-(
g
-lactone)-2-
b
a
a-D
20
From 29b: 10% yield. White powder, mp¼100 ꢂC, [
a
]
ꢁ98 (c
D
From 30a: 12% yield. White powder, mp¼98 ꢂC, [
a
]
20 11.4 (c 0.72,
0.7, CH2Cl2). 1H NMR (300 MHz, CDCl3):
d
¼6.77 (d, J¼8.4 Hz, 1H),
D
CH2Cl2). 1H NMR (300 MHz, CDCl3):
d¼7.01 (d, J¼8.3 Hz, 1H), 6.93
6.74 (d, J¼2.5 Hz, 1H), 6.58 (dd, J¼8.4, 2.6 Hz, 1H), 5.83 (ddd,
J¼17.0, 10.3, 8.2 Hz, 1H), 5.26 (d, J¼3.2 Hz, 1H), 5.13 (br d,
J¼17.4 Hz, 1H), 5.12 (br d, J¼9.5 Hz, 1H), 5.06 (d, J¼3.6 Hz, 1H), 4.52
(d, J¼3.6 Hz, 1H), 4.19 (dd, J¼9.1, 3.2 Hz, 2H), 3.72 (s, 3H), 3.54 (dd,
J¼11.4, 6.5 Hz, 1H), 2.93 (d, J¼10.7 Hz, 1H), 2.79 (1⁄2 AB, J¼12.5 Hz,
1H), 2.68–2.78 (m, 2H), 2.48 (dt, J¼12.1, 7.2 Hz, 1H), 2.21 (1⁄2 AB,
J¼12.2 Hz, 1H), 1.96–2.08 (m, 2H), 1.81–1.93 (m, 4H), 1.65 (qd,
J¼12.4, 5.3 Hz, 1H), 1.51–1.60 (m, 1H), 1.43 (s, 3H), 1.23 (s, 3H), 0.91
(d, J¼2.3 Hz, 1H), 6.67 (dd, J¼8.1, 2.4 Hz, 1H), 5.92 (d, J¼3.7 Hz, 1H),
5.58 (dt, J¼17.0, 9.6 Hz, 1H), 5.34 (d, J¼2.6 Hz, 1H), 5.13 (br d,
J¼17.0 Hz, 1H), 5.09 (br d, J¼9.0 Hz, H), 4.57 (d, J¼3.6 Hz, 1H), 4.14
(dd, J¼9.1, 2.6 Hz, 1H), 4.08 (q, J¼7.3 Hz, 1H), 3.72 (s, 3H), 3.59–3.60
(m,1H), 3.50 (dd, J¼11.0, 5.3 Hz,1H), 3.31–3.33 (m,1H), 3.08 (1⁄2 AB,
J¼11.7 Hz, 1H), 2.86 (td, J¼8.6, 3.9 Hz, 1H), 2.68–2.74 (m, 2H), 2.65
(1⁄2 AB, J¼11.7 Hz, 1H), 2.16–2.28 (m, 2H), 2.09 (d, J¼11.5 Hz, 1H),
1.84–2.04 (m, 3H), 1.52–1.80 (m, 4H), 1.47 (s, 3H), 1.28 (s, 3H), 1.20–
(qd, J¼11.9, 5.3 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3):
¼177.4
d
1.26 (m, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼169.9 (s), 169.7 (s),
(s), 169.4 (s), 158.3 (s), 139.7 (s), 134.6 (s), 134.5 (d), 120.9 (d), 117.8
(t), 115.0 (d), 112.4 (s), 109.8 (d), 105.1 (d), 95.0 (s), 81.5 (d), 79.2
(d), 78.7 (d), 69.0 (d), 64.6 (t), 56.3 (s), 55.4 (q), 53.3 (d), 50.7 (d),
44.1 (d), 41.6 (d), 34.9 (t), 31.9 (t), 30.9 (t), 27.3 (t), 26.8 (q), 26.3
(q), 25.7 (t) ppm.
157.5 (s), 138.7 (s), 137.0 (d), 130.2 (s), 128.9 (d), 117.4 (t), 112.5 (s),
111.4 (d), 105.0 (d), 93.5 (s), 82.7 (d), 78.9 (d), 77.7 (d), 68.4 (d), 64.2
(t), 55.7 (s), 55.4 (q), 50.9 (d), 48.9 (d), 45.2 (d), 44.8 (t), 40.2 (d),
29.7 (t), 27.7 (t), 26.7 (t), 26.6 (q), 26.2 (q), 26.16 (t) ppm.

192
D. Moraleda et al. / Tetrahedron 65 (2009) 177–193
Table 1
Crystal data and structure refinement for 9a, 10a, 11, 9b, 10b, 13, 18a, 22, and 37
Compound
9a
10a
11
9b
10b
13
18a
22
37
Formula
Mw
C24H28O5
396.4
C48H56O10
792.93
C48H56O10
792.93
C24H28O5
396.46
C24H28O5
396.46
C46H62O9
757.9
C35H44O5Si
572.79
C58H60O10
917.06
C32H39Cl3O10
689.98
Crystal color
Crystal size/mm3
Crystal system
Space group
a/Å
Colorless
0.4ꢃ0.2ꢃ0.1
Colorless
0.3ꢃ0.15ꢃ0.1
Colorless
Colorless
Colorless
Colorless
0.4ꢃ0.5ꢃ0.2
Colorless
0.3ꢃ0.1ꢃ0.1
Colorless
Colorless
0.4ꢃ0.3ꢃ0.15 0.3ꢃ0.15ꢃ0.15 0.3ꢃ0.3ꢃ0.2
0.5ꢃ0.3ꢃ0.15 0.3ꢃ0.3ꢃ0.2
Orthorhombic Monoclinic
Monoclinic
P21
Monoclinic
P21
Orthorhombic Monoclinic
P212121
9.3657(1)
11.9569(2)
18.4932(4)
Orthorhombic Monoclinic
Monoclinic
P21
P212121
P21
C2
P212121
P21
7.7442(1)
13.1467(2)
20.5181(4)
9.2413(2)
18.2436(4)
12.7072(4)
96.918(1)
2126.77(9)
2
10.0027(2)
17.7986(5)
12.4305(4)
104.660(1)
2140.9(1)
2
11.525(1)
7.7099(4)
11.905(1)
102.137(5)
1034.2(1)
2
9.4900(2)
19.0420(5)
11.7460(4)
99.1130(1)
2095.81(1)
2
7.815(1)
15.934(1)
27.327(1)
9.7235(1)
12.9429(2)
19.4645(3)
99.8867(6)
2413.23(6)
2
11.1904(2)
10.8096(2)
14.3389(3)
108.2357(6)
1647.38(5)
2
b/Å
c/Å
ꢂ
b
/
V/Å3
2088.95(6)
4
1.261
0.87
2070.96(6)
4
1.272
3402.9(5)
4
1.118
Z
Dc/g cmꢁ3
1.238
0.86
1.23
8.5
1.273
0.88
1.199
0.82
1.26
0.85
1.391
3.34
m
(Mo K
a
)/cmꢁ1
0.88
1.06
No. of unique data
2279
4051
4086
2090
2136
4408
4522
6484
3145
No. of param. refined 263
523
527
265
262
250
371
617
411
R [I>2
wR [unique]
Goodness of fit
Min; max Dr/e Åꢁ3
s
(I)]
0.046 [2099]
0.164a
1.211
0.069 [3557]
0.188b
1.107
0.049 [3383]
0.1279c
1.082
0.052 [1678]
0.120d
1.080
0.040 [1994]
0.115e
1.075
0.066 [3941]
0.159f
1.075
0.084 [2816]
0.222g
1.035
0.060 [4535]
0.198h
1.124
0.040 [3005]
0.132i
1.186
ꢁ0.265; 0.258 ꢁ0.296; 0.048 ꢁ0.148; 0.026 ꢁ0.157; 0.038
ꢁ0.150; 0.024 ꢁ0.134; 0.026 ꢁ0.326; 0.292 ꢁ0.607;0.491 ꢁ0.387; 0.101
w¼1/[
s
2(Fo2)þ(AP)2þBP] where P¼(Fo2þ2F2c)/3.
a
A¼0.1053; B¼0.2277.
b
c
d
e
f
A¼0.1001; B¼0.9663.
A¼0.0555; B¼0.4268.
A¼0.0378; B¼0.4773.
A¼0.0741; B¼0.1601.
A¼0.0629; B¼0.9709.
A¼0.0925; B¼1.1158.
A¼0.1261; B¼0.0.
g
h
i
A¼0.0819; B¼0.3179.
4.29. (8
methoxy-17
isopropylidene-
b
,9
a
,14
-vinylgona-1,3,5(10)-triene (1,2-O-
-glucofuranos-3-yl) ester (39)
a
)-11
b
-Carboxy-11
a
,13
a
-(
g
-lactone)-3-
6.8 Hz, 1H), 1.84–1.92 (m, 2H), 1.48–1.59 (m, 2H), 1.45 (s, 3H), 1.24 (s,
a
3H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼203.3 (s), 173.1 (s), 168.2 (s),
a
-D
157.7 (s), 152.5 (s), 139.0 (s), 114.6 (d), 111.5 (s), 109.4 (d), 104.2 (d),
91.2 (s), 81.2 (d), 78.1 (d), 77.0 (d), 67.6 (d), 63.3 (t), 56.8 (d), 54.6 (q),
54.5 (d), 52.6 (s), 51.6 (d), 42.4 (d), 41.1 (d), 35.8 (t), 29.9 (q), 29.0 (t),
27.1 (t), 26.1 (t), 25.8 (q), 25.2 (q), 25.1 (t) ppm. C31H38O11 (586.6): C
63.47, H 6.53; found C 63.38, H 6.58.
From 30b: 45% yield. White powder, mp¼104 ꢂC. 1H NMR
(300 MHz, CDCl3):
d
¼6.96 (d, J¼8.8 Hz, 1H), 6.61 (dd, J¼8.8, 2.6 Hz,
1H), 6.51 (d, J¼2.6 Hz, 1H), 5.91 (d, J¼3.6 Hz, 1H), 5.81 (ddd, J¼17.2,
9.5, 8.4 Hz,1H), 5.48 (d, J¼3.5 Hz), 5.10 (br d, J¼10.0 Hz,1H), 5.09 (br
d, J¼16.4, 1H), 4.52 (d, J¼3.6 Hz, 1H), 4.38 (dd, J¼8.7, 3.5 Hz, 1H),
4.34 (d, J¼6.9 Hz, 1H), 3.76–3.79 (m, 1H), 3.72 (d, J¼2.8 Hz, 1H), 3.70
(s, 3H), 2.70–2.84 (m, 3H), 2.56 (1⁄2 AB, J¼11.5 Hz, 1H), 2.44–2.50
(m, 2H), 2.38 (1⁄2 AB, J¼11.5 Hz, 1H), 2.08–2.24 (m, 3H), 1.82–1.94
(m, 3H), 1.64 (qd, J¼11.6, 4.7 Hz, 1H), 1.50 (s, 3H), 1.29 (s, 3H) ppm.
4.32. X-ray crystallography
CCDC-686694 (for 9a), CCDC-686695 (for 10a), CCDC-686692 (for
11),CCDC-686693(for9b),CCDC-686696(for10b),CCDC-686689(for
13), CCDC-686690(for18a), CCDC-686691(for22), andCCDC-686697
(for 37) contain the supplementary crystallographic data for this pa-
per. Thesedatacanbeobtainedfreeofchargeatwww.ccdc.cam.ac.uk/
conts/retrieving.html [or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: þ44 1223 336
033; or e-mail: deposit@ccdc.cam.ac.uk]. A summary of the crystal
data, data collection, and refinements is given in Table 1.
13C NMR (75 MHz, CDCl3):
d¼174.0 (s), 171.1 (s), 157.9 (s), 138.1 (s),
134.9 (d), 131.2 (d), 124.6 (s), 117.4 (t), 113.9 (d), 112.5 (s), 112.0 (d),
105.3 (d), 92.7 (s), 83.5 (d), 79.4 (d), 79.0 (d), 68.8 (d), 64.6 (t), 57.7
(s), 55.2 (q), 51.5 (d), 45.6 (d), 40.9 (t), 39.3 (d), 34.9 (d), 31.6 (t), 30.3
(t), 26.8 (q), 26.5 (q), 24.9 (t), 24.7 (t) ppm. C31H38O10 (570.6): C
65.25, H 6.71; found C 65.18, H 6.68.
Acknowledgements
4.30. Wacker-type oxidation of 29b
D.M. is grateful to the MEN for a grant. This work has been fi-
nancially supported by the CNRS and the Ministe`re de l’Education
Nationale. We thank P. Guenot (CRMPO, Rennes, Fr) for his analyses
and Prof. C. Roussel for the ee determinations. We are indebted to
The methodology is similar to that described for the oxidation
of 13.
4.31. (8
-lactone)-3-methoxygona-1,3,5(10)-triene (1,2-O-
isopropylidene- -glucofuranos-3-yl) ester (40)
a,9b,14b)-17b-Acetyl-11a-carboxy-11b,13b-
´
Dr. B. Vacher (Pierre Fabre Medicaments, Castres, Fr) for helpful
(g
comments.
a-D
Yield 20%. 1H NMR (500 MHz, CDCl3):
d
¼6.88 (d, J¼8.4 Hz, 1H),
References and notes
6.76 (d, J¼2.5 Hz, 1H), 6.67 (dd, J¼8.4, 2.7 Hz, 1H), 5.80 (d, J¼3.6 Hz,
1H), 5.28 (s, 2H), 5.20 (d, J¼2.8 Hz, 1H), 4.23 (d, J¼3.1 Hz, 1H), 4.11
(dd, J¼8.67, 2.83 Hz, 1H), 3.74 (s, 3H), 3.52 (1⁄2 AB, J¼11.5, 3.5 Hz,
1H), 3.42 (1⁄2 AB, J¼11.5, 5.9 Hz, 1H), 3.13 (tt, J¼5.3, 3.7 Hz, 1H), 3.07
(d, J¼11.2 Hz, 1H), 2.93 (d, J¼7.6 Hz, 1H), 2.70–2.80 (m, 2H), 2.48 (d,
J¼12.3 Hz, 1H), 2.25 (s, 3H), 2.13–2.20 (m, 2H), 1.98 (td, J¼11.2,
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