The morita-baylis-hillman reaction of chiral highly oxygenated cyclopent-2-enones

Article abstract of DOI:10.1002/hlca.201200421

The Morita-Baylis-Hillman (MBH) reactions of (4S,5R,7R,8R)- and (4R,5R,7R,8R)-4-hydroxy-7,8-dimethoxy-7,8-dimethyl-6,9-dioxaspiro[4.5] dec-2-en-1-ones (2 and 3, resp.) with aldehydes using various catalysts were studied. A combination of Bu₃P/phenol in THF was found being optimum conditions giving the corresponding MBH adducts with high diastereoisomeric ratios. After separation, each stereomerically pure isomer of the MBH adducts was subjected to hydrolysis employing 1% aq. CF₃COOH (TFA) in a water bath of an ultrasonic cleaner to afford the corresponding polyhydroxylated cyclopentenones in good yields. Copyright

Full text of DOI:10.1002/hlca.201200421

1912
Helvetica Chimica Acta – Vol. 95 (2012)
The MoritaꢀBaylisꢀHillman Reaction of Chiral Highly Oxygenated
Cyclopent-2-enones
by Chonticha Masusaia), Darunee Soorukrama), Chutima Kuhakarna), Patoomratana Tuchindaa),
Chaveng Pakawatchaib), Vichai Reutrakula), and Manat Pohmakotr*a)
a) Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science,
Mahidol University, Rama VI Road, Bangkok 10400, Thailand
(phone: þ 66-2-2015158; fax: þ 66-2-6445126; e-mail: manat.poh@mahidol.ac.th)
b) Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science,
Prince of Songkla University, Hat Yai, Songkla 90112, Thailand
Dedicated to Professor Dieter Seebach on the occasion of his 75th birthday
The MoritaꢀBaylisꢀHillman (MBH) reactions of (4S,5R,7R,8R)- and (4R,5R,7R,8R)-4-hydroxy-7,8-
dimethoxy-7,8-dimethyl-6,9-dioxaspiro[4.5]dec-2-en-1-ones (2 and 3, resp.) with aldehydes using various
catalysts were studied. A combination of Bu3P/phenol in THF was found being optimum conditions
giving the corresponding MBH adducts with high diastereoisomeric ratios. After separation, each
stereomerically pure isomer of the MBH adducts was subjected to hydrolysis employing 1% aq.
CF3COOH (TFA) in a water bath of an ultrasonic cleaner to afford the corresponding polyhydroxylated
cyclopentenones in good yields.
Introduction. – The MoritaꢀBaylisꢀHillman (MBH) reaction [1] is an efficient
method used for creating C,C bond between the a-C-atom of electron-deficient alkenes
with aldehydes and activated aldimines. The reaction is typically catalyzed by a wide
range of organocatalysts such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-
diazabicyclo[2.2.2]octane (DABCO), phosphines [2], and Lewis acids [3], providing a-
functionalized activated alkenes. Synthetic applications of the MBH and aza-MBH
adducts (functionalized allylic alcohols and amines, resp.) in organic synthesis have
been extensively demonstrated [4]. Due to the versatilities of the MBH adducts as
useful building blocks for the synthesis of complex natural products, studies towards
asymmetric version of the MBH reactions have attracted considerable attention. By
employing chiral amines, chiral Lewis acids, or chiral Brønsted acids as promoters,
asymmetry can be achieved during the C,C bond formation, thus resulting in
enantiomerically enriched MBH adducts [5]. Even though diastereoselective MBH
reactions have been well-documented, few reports dealt with diastereoselective MBH
reactions using chiral activated alkenes [4a][6]. We have recently reported an
asymmetric synthesis of chiral oxygenated cyclopentenones 2 and 3 [7] from the chiral
ester 1 [8], of which the synthetic sequence was based upon the intramolecular
cyclization of a-sulfinyl carbanion as the key step. Compounds 2 and 3 were converted
to the corresponding (ꢀ)-pentenomycin I and (ꢀ)-epipentenomycin I, and their
analogs (Scheme 1) [7]. In a continuation of our research in this area [7][9], we report
herein the study of the synthesis of chiral highly oxygenated cyclopent-2-enones
ꢀ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 95 (2012)
1913
Scheme 1
involving Lewis base-mediated MBH reactions. It is anticipated that compounds 2 and
3 can be used as useful chiral starting oxygenated cyclopentenones for preparing
compound of types 6 and 7, which may be important synthons for further synthetic
manipulations. Therefore, the present report involves diastereoselective MBH
reactions between chiral oxygenated cyclopentenones 2 and 3 with various aldehydes.
Results and Discussion. – Initially, the reaction of 2 with benzaldehyde (PhCHO)
employing several Lewis base catalysts such as DABCO, DMAP, Bu3P, Cy3P, and Ph3P
was investigated. The reaction performed using 20 mol-% of DABCO in the presence
of PhOH in THFat room temperature for 10 d did not give the MBH adduct 4a, and the
starting compound 2 was recovered in 73% yield (Table 1, Entry 1). Gratifyingly, when
20 mol-% of Bu3P was used in place of DABCO, the desired adduct 4a was obtained in
73% as a mixture of two diastereoisomers (4aA/4aB 88 :12) along with starting
compound 2 (19%; Table 1, Entry 2). The two diastereoisomers of 4a can be readily
separated by preparative thin-layer chromatography (PLC; SiO2) to afford 4aA and
4aB as the major and minor products, respectively. The reactions employing
tricyclohexylphosphine (Cy3P) and Ph3P gave inferior results and lower yields of the
expected MBH adduct 4a (23 and 13% resp.; Table 1, Entries 3 – 4). It is worth noting
that, even though the use of Ph3P gave the adduct 4a in low yield, the reaction was
highly diastereoselective affording 4a as a single diastereoisomer.
After identifying an appropriate promoters (Bu3P/phenol; Table 1, Entry 2), we
then further examined the effect of choice of solvent on the diastereoselectivity of the
reaction (Table 2). The reaction performed in both AcOEt and CH2Cl2 gave moderate
yields of 4a (56 and 64%, resp.) with low diastereoselectivity (Table 2, Entries 1 and 2).
Both yield and diastereoselectivity were deteriorated, when the reactions were carried
out in toluene, acetone, MeOH, and MeCN (Table 2, Entries 3 – 6). Although THF
afforded 4a in low yield, good diastereoselectivity was obtained (Table 2, Entry 7).

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Helvetica Chimica Acta – Vol. 95 (2012)
Table 1. Optimization of the MBH Reaction between Compound 2 and Benzaldehyde by Employing
Various Catalysts
Entry
Reaction conditionsa)
4a [%]b)
2 [%]b)
dr of 4ac)
1
2
3
4
DABCO, PhOH, THFd)
Bu3P, PhOH, THFd)
Cy3P, PhOH, toluene
Ph3P, PhOH, THF
0
73
23
13
73
19
64
83
–
88 : 12
73 : 27
100 : 0
a) Unless stated otherwise, the reactions were carried out by using 1 equiv. of 2 (0.2 mmol), 1 equiv. of
PhCHO, 20 mol-% of catalyst and PhOH at room temperature for 10 d. b) Yields of isolated products.
c) Determined after separation by PLC (SiO2). d) 1.5 Equiv. of PhCHO was used.
Table 2. Solvent Effect on the Diastereoselectivity of the MBH Reaction of 2 with PhCHO
Entrya)
Solvent
4a [%]b)
2 [%]b)
dr of 4ac)
1
2
3
4
5
6
7
AcOEt
CH2Cl2
Toluene
Acetone
MeOH
MeCN
THF
56
64
16
21
32
29
17
9
13
14
12
37
23
67
55 : 45
58 : 42
35 : 65
51 : 49
36 : 64
39 : 61
84 : 16
a) The reaction on 0.1-mmol scale of 2 by using PhCHO (1.5 equiv.), Bu3P (20 mol-%), PhOH (20 mol-
%), and solvent (1 ml) was performed for 24 h. b) Yields of isolated products. c) Determined after
separation by PLC (SiO2).
To further optimize the reaction conditions, the reaction temperature and reaction
time were varied. Comparable results were observed, when the reactions of 2 and
PhCHO were carried out at room temperature for 15 and 24 h, respectively (Table 3,
Entries 1 and 2). Adduct 4a was obtained in good yield with good diastereoselectivity.
High reaction temperature (refluxing THF for 16 h) was found harmful to the reaction,
leading to lower yield and diastereoselectivity (Table 3, Entry 3). Neither yield nor
diastereoselecitvity was improved, when the reactions were carried out at prolonged
reaction times (168 and 240 h, resp.; Table 3, Entries 4 and 5).
From the results compiled in Tables 1 – 3, the optimum conditions for the reaction
of 2 with PhCHO are the presence of Bu3P (20 mol-%), PhOH (20 mol-%), and THF,
and room temperature for 24 h. These conditions were employed as optimized reaction
conditions for the exploration of the applicability of compounds 2 and 3 as chiral
activated alkenes in the MBH reaction with various aromatic and aliphatic aldehydes
(Table 4, Entries 1 – 9 and 10 – 14, resp.). The results collected in Table 4 revealed that

Helvetica Chimica Acta – Vol. 95 (2012)
1915
Table 3. Optimization for the Reaction Time of the MBH Reaction of 2 with PhCHO Using 20 mol-% of
Bu3P and PhOH at Room Temperature
Entrya)
Time [h]
4a [%]b)
2 [%]b)
dr of 4ac)
1
2
3d)
4
15
24
16
168
240
64
69
44
70
77
6
10
15
7
88 : 12
88 : 12
66 : 34
73 : 27
79 : 21
5
13
a) The reaction was performed on 0.2-mmol scale in degassed THF (2 ml). b) Yields of isolated products.
c) Determined after separation on PLC (SiO2). d) The reaction was performed under refluxing in THF.
the reactions of compounds 2 and 3 with benzaldehydes having both electron-
withdrawing and electron-donating substituents readily proceeded with moderate-to-
high diastereoselectivites and afforded the corresponding adducts 4 and 5 in moderate-
to-good yields, together with the recovery of starting material in almost all cases
(Table 4, Entries 2 – 8). With an heteroaromatic aldehyde, an a,b-unsaturated
aldehyde, and aliphatic aldehydes, the reactions of compound 2 were not efficient,
and the corresponding MBH adducts 4 were obtained in lower yields with low-to-
moderate diastereoselectivities (Table 4, Entries 10 – 14). It should be mentioned that
the two diastereoisomers of each adduct can be separated by PLC. The absolute
configuration of the major isomer of 4a, i.e., 4aA, was determined by X-ray
crystallography (Fig.), and the configuration of the newly created stereogenic center
of 4aA was assigned as (S)1). The observed stereochemical outcomes of compound
4aA can be rationalized by closed transition state of ZimmermanꢀTraxler model as
Figure. X-Ray Structure of the Major Diastereoisomer of 4a (4aA)
1
)
CCDC-893001 contains the supplementary crystallographic data for this article. These data can be
obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif.

1916
Helvetica Chimica Acta – Vol. 95 (2012)
Table 4. The MBH Reaction of Chiral Oxygenated Cyclopentenones 2 and 3 with Aldehydes to Give the
Corresponding Adducts 4 and 5
Entry RCHO
Enone
2 or 3a)
Adducts
Yield [%]b)
2 or 3
[%]b)
A
B
1
2
3
4
5
Benzaldehyde
2
3
2
3
2
3
2
3
2
3
2
2
3
2
2
2
2
2
2
2
4a (R ¼ Ph)
61
37
55
67
50
41
38
52
40
46
38
23
46
23
8
10
9
6
5a (R ¼ Ph)
24
32
22
21
27
35
9
4-Nitrobenzaldehyde
4-Chlorobenzaldehyde
3-Methoxybenzaldehyde
4-Methylaldehyde
4b (R ¼ 4-NO2ꢀC6H4)
5b (R ¼ 4-NO2ꢀC6H4)
4c (R ¼ 4-ClꢀC6H4)
5c (R ¼ 4-ClꢀC6H4)
4d (R ¼ 3-MeOꢀC6H4)
5d (R ¼ 3-MeOꢀC6H4)
4e (R ¼ MeꢀC6H4)
5e (R ¼ MeꢀC6H4)
4f (R ¼ 2-ClꢀC6H4)
4g (R ¼ 4-MeOꢀC6H4)
5g (R ¼ 4-MeOꢀC6H4)
4h (R ¼ Furan-2-yl)
–
15
13
14
23
32
22
10
32
27
7
21
13
15
14
–
5
12
32
9
5
35
8
21
36
10
38
28
6
7
2-Chlorobenzaldehyde
p-Anisaldehyde
8
9
Furan-2-carbaldehyde
2,3-Dimethoxybenzaldehyde
Cinnamaldehyde
Propionaldehyde
Isobutyraldehyde
4i (R ¼ 2,3-(MeO)2ꢀC6H3) 57
10
11
12
13
14
4j (R ¼ PhꢀCH¼CH)
4k (R ¼ Et)
22
37
34
31
22
4l (R ¼ iPr)
Butyraldehyde
4m (R ¼ Pr)
Hydrocinnamaldehyde
(¼ 3-phenylpropanal)
4n (R ¼ PhꢀCH2CH2)
15
a) The reaction on 0.2-mmol scale was carried out. b) Yields of isolated products.
shown in Scheme 2. The reaction of 2 with PhCHO and other aldehydes was proposed
to proceed through transition states C and D as depicted in Scheme 2. The transition
state C is energetically more favorable than the transition state D due to minimized
steric repulsion between the OH and R groups.
Having the MBH adducts 4 and 5 in hand, we have briefly studied the synthetic
utilities of these adducts for the preparation of the corresponding polyhydroxylated
cyclopentenones 6 and 7, respectively. Thus, compound 4aA as a single stereoisomer
was subjected to hydrolysis mediated by 1% aq. CF3COOH (TFA) to afford the
expected polyhydroxylated cyclopentenone 6a in good yield as a 3.8 :1 mixture of two
diastereoisomers (Table 5, Entry 1). This implies that epimerization at the stereogenic
benzylic C-atom carrying the acidic H-atom took place under the reaction conditions.
The reaction of 4aB and 4mB were also carried out under similar reaction conditions

Helvetica Chimica Acta – Vol. 95 (2012)
1917
Scheme 2. Proposed Transition State of the MBH Reaction of 2 with Aldehyde
leading to similar results (Table 5, Entry 2 and 3, resp.). Diastereoisomer ratio (dr)
6aA/6aB was determined by integration of the signal of HOꢀC(4) of the major isomer
(4.67 (d, J ¼ 4.7 for 6aA) and 4.72 (dd, J ¼ 4.4, 1.5 for 6aB)) and of the minor isomer
(4.69 (d, J ¼ 4.7 for 6aA) and 4.64 (dd, J ¼ 4.4, 1.5 for 6aB)). Whereas, dr of 6mB/
6mA was determined by integration of the signal of HꢀC(3) of the major isomer (7.19
(t, J ¼ 1.7)) and of the minor isomer (7.22 (t, J ¼ 1.7)).
To our delight, the hydrolysis of 4eA, 4fB, 5dA, 5dB, and 5eA with 1% aq. TFA
using water bath of an ultrasonic cleaner at 40 – 608 for 3 h gave 6eA, 6fB, 7dA, 7dB,
Table 5. Hydrolysis of the MBH Adducts 4 or 5
Entry
MBH Adducts
Reaction conditions
Hydrolysis adducts
Yield [%]a)
1
2
3
4
5
6
7
8
4aA
4aB
4mB
4eA
4fB
5dA
5dB
5eA
1% aq. TFA, r.t., 5 h
1% aq. TFA, r.t., 5 h
1% aq. TFA, r.t., 5 h
1% aq. TFA, sonicationd)
1% aq. TFA, sonicationd)
1% aq. TFA, sonicationd)
1% aq. TFA, sonicationd)
1% aq. TFA, sonicationd)
6aA
6aB
6mB
6eA
6fB
7dA
7dB
7eA
66b)
76b)
82c)
78
72
74
63
49
a) Yields of isolated products. b) Diastereoisomer ratio 3.8 : 1, determined by 1H-NMR. c) Diaster-
eoisomer ratio 7.7: 1, determined by H-NMR. d) 35 kHz, 120/480 W, 40 – 608, 3 h.
1

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Helvetica Chimica Acta – Vol. 95 (2012)
and 7eA in 78, 72, 74, 63, and 49% yield; each as a single isomer, respectively (Table 5,
Entries 4 – 8).
In addition, attempts to perform hydrolysis of 4aA using Dowex 50 WꢀX8
(Hþ-form) [10] in MeOH at room temperature for 24 h resulted in the formation of
compound 8a in 83% yield as a 1:1 mixture of diastereoisomers the ratio of which was
determined by integration of the signals of benzylic H-atoms at 4.98 (s) and 4.96
(s) ppm. We assume that compound 8a was derived from the formation of a benzylic
carbonium ion under the reaction conditions, followed by an SN2’ addition of MeOH
(Scheme 3).
Scheme 3
Finally, our efforts to perform oxidation of 4a to the expected triketo derivative 9a
by employing several oxidizing agents such as PCC, PDC, IBX, DIB, DMP, MnO2,
FeCl3, DDQ, TEMPO, and Swern oxidation were unsuccessful. In all cases, a complex
mixture of products was obtained (Scheme 4).
Scheme 4
Conclusion. – We have reported that C(2)-hydroxyalkylation of (4S,5R,7R,8R)- and
(4R,5R,7R,8R)-4-hydroxy-7,8-dimethoxy-7,8-dimethyl-6,9-dioxaspiro[4.5]dec-2-en-1-
ones (2 and 3, resp.) can be achieved through the MoritaꢀBaylisꢀHillman reaction with
high diastereoselectivity. The diastereofacial selectivity of the reaction can be
explained by the ZimmermanꢀTraxler model. We have also demonstrated that the
resulting MBH adducts can be converted to highly chiral oxygenated cyclopent-2-
enones. Due to particular flexibility and ease of the methodology, asymmetric C(2)-
branched, highly oxygenated cyclopentenone adducts can be accessed, and they may be
found useful as chiral synthons for organic synthesis.
We acknowledge financial supports from the Thailand Research Fund (BRG 5380019), the Office of
the Higher Education Commission and Mahidol University under the National Research Universities
Initiative, and the Center of Excellence for Innovation in Chemistry (PERCH-CIC).

Helvetica Chimica Acta – Vol. 95 (2012)
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Experimental Part
General. Compounds 2 and 3 were synthesized according to the literature [7]. The org. solvents were
dried over appropriate drying agents and distilled prior to use. TLC and prep. layer chromatography
(PLC): silica gel (SiO2); visualization with UV light. Column chromatography (CC): SiO2 (60 – 120
mesh). M.p.: Bꢀchi 501 melting-point apparatus, uncorrected. Bath of an ultrasonic cleaner: Bandelin
SONOREX Digital 10P. Optical rotation: Jasco P-1020 polarimeter. IR Spectra: Jasco A-302 or Perkin-
1
Elmer 683 spectrometer; in KBr, or CHCl3, or neat. H- and 13C-NMR: Bruker DPX-300 at 300 and
75 MHz, resp., or Bruker 500 at 500 and 125 MHz, resp., in CDCl3 or (D6)acetone with Me4Si as an
internal standard; chemical shifts (d) downfield from Me4Si; coupling constants (J) in Hz. MS: Thermo
Finnigan Polaris Q mass spectrometer. HR-MS: HR-TOF-MS Micromass model VQ-TOF 2 or Finnigan
MAT 95 mass spectrometer. X-ray crystallographic analysis: Kappa CCD.
The MBH Reaction of 2 and 3. General Procedure: A mixture of 2 or 3 (0.2 mmol), aldehyde
(0.35 mmol), and 20 mol-% of PhOH in dry THF was degassed and then cooled to 158. In a separated
flask, a soln. of 20 mol-% of Bu3P in dry THF was degassed and then added to the above mixture via
cannula. The mixture was allowed to warm up to r.t. and stirred for 24 h. The solvent was removed in
vacuo, and the crude product was purified by PLC (SiO2, 20% AcOEt/CH2Cl2 (3ꢁ) and 30% AcOEt/
hexanes (3ꢁ) for 2 and 3, resp.).
(4S,5R,7R,8R)-4-Hydroxy-2-[(S)-hydroxy(phenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxa-
spiro[4.5]dec-2-en-1-one (4aA). Less polar. Yield: 44.5 mg (61%). White solid. M.p. 154 – 1558. [a]D25
¼
ꢀ30 (c ¼ 1.02, CHCl3). IR (KBr): 3385, 3271, 1720, 1455, 1215, 1038. 1H-NMR (300 MHz, CDCl3): 7.34 –
7.29 (m, 5 H); 7.18 (t, J ¼ 1.6, 1 H); 5.53 (s, 1 H); 4.90 (s, 1 H); 4.08 (d, J ¼ 11.0, 1 H); 3.81 (d, J ¼ 11.0,
1 H); 3.47 (s, 3 H); 3.42 (s, 3 H); 3.46 – 3.35 (br., OH); 3.17 – 3.00 (br., OH); 1.43 (s, 3 H); 1.36 (s, 3 H).
13C-NMR (75 MHz, CDCl3): 201.8; 154.2; 147.0; 140.2; 128.7 (2ꢁ); 128.3; 126.6 (2ꢁ); 100.6; 100.5; 82.5;
78.5; 69.6; 60.2; 49.4; 48.6; 18.9; 18.7. MS: 364 (1, Mþ), 333 (43, [M ꢀ MeO]þ). HR-MS: 387.1412 ([M þ
Na]þ, C19H24NaOþ7 ; calc. 387.1420).
(4S,5R,7R,8R)-4-Hydroxy-2-[(R)-hydroxy(phenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxa-
spiro[4.5]dec-2-en-1-one (4aB). More polar. Yield: 6.1 mg (8%). White solid. M.p. 176 – 1788. [a]D25
¼
ꢀ75.5 (c ¼ 0.99, CHCl3). IR (KBr): 3434, 1703, 1456, 1226, 1145, 1109, 1033. 1H-NMR (300 MHz,
CDCl3): 7.39 – 7.32 (m, 5 H); 7.18 (t, J ¼ 1.7, 1 H); 5.54 (s, 1 H); 4.88 (s, 1 H); 4.17 (d, J ¼ 11.0, 1 H); 3.90
(d, J ¼ 11.0, 1 H); 3.43 (s, 3 H); 3.39 (s, 3 H); 3.29 (d, J ¼ 2.6, OH); 3.12 – 2.62 (br., OH); 1.43 (s, 3 H); 1.33
(s, 3 H). 13C-NMR (75 MHz, CDCl3): 201.9; 154.4; 147.0; 140.3; 128.6 (2ꢁ); 128.2; 126.5 (2ꢁ); 100.6
(2ꢁ); 82.1; 78.6; 69.6; 60.3; 49.4; 48.5; 18.9; 18.7. MS: 364 (1, Mþ), 333 (20, [M ꢀ MeO]þ). HR-MS:
387.1431 ([M þ Na]þ, C19H24NaOþ7 ; calc. 387.1420).
(4S,5R,7R,8R)-4-Hydroxy-2-[(S)-hydroxy(4-nitrophenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-6,9-
dioxaspiro[4.5]dec-2-en-1-one (4bA). Less polar. Yield: 44.7 mg (55%). White solid. M.p. 182 – 1838.
[a]2D5 ¼ ꢀ60.4 (c ¼ 0.91, CHCl3). IR (KBr): 3509, 3455, 1717, 1608, 1514, 1354, 1213, 1145, 1114, 1037.
1H-NMR (300 MHz, CDCl3): 8.23 (d, J ¼ 8.8, 2 H); 7.58 (d, J ¼ 8.8, 2 H); 7.17 (dd, J ¼ 2.2, 1.3, 1 H); 5.66
(s, 1 H); 4.91 (d, J ¼ 1.9, 1 H); 4.29 (d, J ¼ 11.0, 1 H); 4.09 (d, J ¼ 11.0, 1 H); 3.46 (s, 3 H); 3.42 (s, 3 H);
3.36 (s, 1 H); 3.35 (s, 1 H); 1.42 (s, 3 H); 1.35 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 201.7; 154.9; 147.8;
147.3; 146.0; 127.3 (2ꢁ); 123.9 (2ꢁ); 100.7, 100.6; 82.3; 78.5; 68.6; 60.1; 49.4; 48.6; 18.9; 18.7. MS: 409 (1,
Mþ), 378 (28, [M ꢀ MeO]þ). HR-MS: 432.1266 ([M þ Na]þ, C19H23NNaO9þ ; calc. 432.1271).
(4S,5R,7R,8R)-4-Hydroxy-2-[(R)-hydroxy(4-nitrophenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-6,9-
dioxaspiro[4.5]dec-2-en-1-one (4bB). More polar. Yield: 26.5 mg (32%). White solid. M.p. 220 – 2218.
[a]2D5 ¼ ꢀ42.0 (c ¼ 0.54, CHCl3). IR (KBr): 3457, 1709, 1608, 1529, 1350, 1108. 1H-NMR (300 MHz,
CDCl3): 8.23 (d, J ¼ 8.8, 2 H); 7.60 (d, J ¼ 8.8, 2 H); 7.25 (s, 1 H); 5.64 (s, 1 H); 4.89 (s, 1 H); 4.14 (d, J ¼
11.0, 1 H); 3.88 (d, J ¼ 11.0, 1 H); 3.43 (s, 3 H); 3.38 (s, 3 H); 3.57 – 3.30 (br., 2 H); 1.43 (s, 3 H); 1.32 (s,
3 H). 13C-NMR (75 MHz, CDCl3): 201.7; 155.0; 147.7; 147.4; 146.1; 127.3 (2ꢁ); 123.8 (2ꢁ); 100.7; 100.6;
82.0; 78.6; 68.5; 60.1; 49.4; 48.5; 18.8; 18.7. MS: 405 (38, [M ꢀ 3]þ). HR-MS: 432.1276 ([M þ Na]þ,
C19H23NNaOþ9 ; calc. 432.1271).
(4S,5R,7R,8R)-2-[(S)-(4-Chlorophenyl)hydroxymethyl]-4-hydroxy-7,8-dimethoxy-7,8-dimethyl-6,9-
dioxaspiro[4.5]dec-2-en-1-one (4cA). Less polar. Yield: 39.7 mg (50%). White solid. M.p. 141 – 1428.
[a]2D5 ¼ ꢀ7.5 (c ¼ 0.90, CHCl3). IR (KBr): 3379, 1717, 1648, 1377, 1032. 1H-NMR (300 MHz, CDCl3):

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Helvetica Chimica Acta – Vol. 95 (2012)
7.35 – 7.28 (m, 4 H); 7.16 (s, 1 H); 5.50 (s, 1 H); 4.88 (s, 1 H); 4.06 (d, J ¼ 11.0, 1 H); 3.79 (d, J ¼ 11.0, 1 H);
3.45 (s, 3 H); 3.41 (s, 3 H); 3.45 – 3.41 (br., OH); 3.33 – 3.10 (br., OH); 1.42 (s, 3 H); 1.35 (s, 3 H).
13C-NMR (75 MHz, CDCl3): 201.7; 154.3; 146.8; 138.8; 134.0; 128.8 (2ꢁ); 127.9 (2ꢁ); 100.6; 100.5; 82.3;
78.4; 68.9; 60.1; 49.3; 48.6; 18.9; 18.7. MS: 398 (0.5, Mþ), 367 (5, [M ꢀ MeO]þ). HR-MS: 421.1025 ([M þ
Na]þ, C19H23ClNaOþ7 ; calc. 421.1030).
(4S,5R,7R,8R)-2-[(R)-(4-Chlorophenyl)hydroxymethyl]-4-hydroxy-7,8-dimethoxy-7,8-dimethyl-6,9-
dioxaspiro[4.5]dec-2-en-1-one (4cB). More polar. Yield: 17.0 mg (21%). White solid. M.p. 177 – 1788.
1
[a]2D5 ¼ ꢀ47.4 (c ¼ 0.91, CHCl3). IR (KBr): 3455, 1707, 1145, 1105, 1035. H-NMR (300 MHz, CDCl3):
7.34 (s, 4 H); 7.18 (dd, J ¼ 2.3, 1.3, 1 H); 5.51 (s, 1 H); 4.88 (t, J ¼ 1.9, 1 H); 4.16 (d, J ¼ 11.0, 1 H); 3.88 (d,
J ¼ 11.0, 1 H); 3.43 (s, 3 H); 3.39 (s, 3 H); 3.18 – 2.83 (br., OH); 1.43 (s, 3 H); 1.33 (s, 3 H). 13C-NMR
(75 MHz, CDCl3): 201.8; 154.5; 146.7; 138.8; 134.0; 128.8 (2ꢁ); 127.9 (2ꢁ); 100.6 (2ꢁ); 82.0; 78.6; 68.9;
60.2; 49.4; 48.5; 18.9; 18.7. MS: 398 (3, Mþ). HR-MS: 421.1057 ([M þ Na]þ, C19H23ClNaOþ7 ; calc.
421.1030).
(4S,5R,7R,8R)-4-Hydroxy-2-[(S)-hydroxy(3-methoxyphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (4dA). Less polar. Yield: 29.8 mg (38%). White semi-solid. [a]D25
¼
1
ꢀ56.6 (c ¼ 0.96, CHCl3). IR (KBr): 3455, 1720, 1601, 1458, 1261, 1034. H-NMR (300 MHz, CDCl3):
7.27 (t, J ¼ 8.2, 1 H); 7.17 (dd, J ¼ 2.2, 1.4, 1 H); 6.94 – 6.92 (m, 2 H); 6.85 (ddd, J ¼ 8.2, 2.5, 1.0, 1 H); 5.51
(s, 1 H); 4.90 (s, 1 H); 4.11 (d, J ¼ 11.0, 1 H); 3.82 (d, J ¼ 11.0, 1 H); 3.81 (s, 3 H); 3.48 (s, 3 H); 3.43 (s,
3 H); 3.40 – 3.33 (br., OH); 3.17 – 3.03 (br., OH); 1.43 (s, 3 H); 1.36 (s, 3 H). 13C-NMR (75 MHz, CDCl3):
201.8; 159.9; 154.4; 146.9; 141.8; 129.7; 118.8; 113.9; 112.0; 100.6; 100.5; 82.5; 78.5; 69.5; 60.3; 55.2; 49.4;
48.6; 18.9; 18.7. MS: 394 (2, Mþ), 363 (35, [M – MeO]þ). HR-MS: 417.1527 ([M þ Na]þ, C20H26NaOþ8 ;
calc. 417.1525).
(4S,5R,7R,8R)-4-Hydroxy-2-[(R)-hydroxy(3-methoxyphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (4dB). More polar. Yield: 27.7 mg (35%). White solid. M.p. 150 – 1518.
[a]2D5 ¼ ꢀ103.7 (c ¼ 0.62, CHCl3). IR (KBr): 3402, 1724, 1610, 1489, 1287, 1034. 1H-NMR (300 MHz,
CDCl3): 7.28 (t, J ¼ 8.2, 1 H); 7.18 (dd, J ¼ 2.2, 1.3, 1 H); 6.97 – 6.95 (m, 2 H); 6.85 (ddd, J ¼ 8.2, 2.5, 0.9,
1 H); 5.51 (s, 1 H); 4.87 (s, 1 H); 4.16 (d, J ¼ 11.0, 1 H); 3.90 (d, J ¼ 11.0, 1 H); 3.82 (s, 3 H); 3.43 (s, 3 H);
3.39 (s, 3 H); 3.35 – 3.27 (br., OH); 3.13 – 2.97 (br., OH); 1.43 (s, 3 H); 1.33 (s, 3 H). 13C-NMR (75 MHz,
CDCl3): 202.0; 160.0; 154.5; 147.0; 141.9; 129.7; 118.9; 113.9; 112.1; 100.6 (2ꢁ); 81.9; 78.4; 69.3; 60.3; 55.4;
49.4; 48.6; 18.9; 18.7. MS: 394 (2, Mþ), 363 (49, [M ꢀ MeO]þ). HR-MS: 417.1523 ([M þ Na]þ,
C20H26NaOþ8 ; calc. 417.1525).
(4S,5R,7R,8R)-4-Hydroxy-2-[(S)-hydroxy(4-methylphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-6,9-
dioxaspiro[4.5]dec-2-en-1-one (4eA). Less polar. Yield: 30.2 mg (40%). White solid. M.p. 154 – 1558.
[a]2D5 ¼ ꢀ0.6 (c ¼ 1.12, CHCl3). IR (KBr): 3274, 1721, 1150, 1109, 1039. 1H-NMR (300 MHz, CDCl3): 7.25
(d, J ¼ 8.0, 2 H); 7.20 (t, J ¼ 1.9, 1 H); 7.17 (d, J ¼ 8.0, 2 H); 5.50 (s, 1 H); 4.91 (d, J ¼ 1.9, 1 H); 4.10 (d, J ¼
10.9, 1 H); 3.81 (d, J ¼ 10.9, 1 H); 3.49 (s, 3 H); 3.44 (s, 3 H); 3.34 (d, J ¼ 2.7, 1 H); 2.88 (d, J ¼ 3.0, 1 H);
2.35 (s, 3 H); 1.43 (s, 3 H); 1.36 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 201.7; 154.1; 147.2; 138.1; 137.3;
129.4 (2ꢁ); 126.5 (2ꢁ); 100.7; 100.6; 82.7; 78.6; 69.6; 60.4; 49.4; 48.6; 21.1; 18.9; 18.7. MS: 347 (19, [M ꢀ
MeO]þ). HR-MS: 401.1573 ([M þ Na]þ, C20H26NaOþ7 ; calc. 401.1576).
(4S,5R,7R,8R)-4-Hydroxy-2-[(R)-hydroxy(4-methylphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (4eB). More polar. Yield: 3.7 mg (5%). White solid. M.p. 171 – 1728.
1
[a]2D5 ¼ ꢀ19.7 (c ¼ 0.69, CHCl3). IR (KBr): 3448, 1706, 1145, 1108, 1035. H-NMR (500 MHz, CDCl3):
7.28 (d, J ¼ 8.0, 2 H); 7.20 (t, J ¼ 1.3, 1 H); 7.18 (d, J ¼ 8.0, 2 H); 5.50 (s, 1 H); 4.88 (s, 1 H); 4.17 (d, J ¼
11.0, 1 H); 3.90 (d, J ¼ 11.0, 1 H); 3.44 (s, 3 H); 3.40 (s, 3 H); 3.37 – 3.30 (br., OH); 3.00 – 2.82 (br., OH);
2.36 (s, 3 H); 1.44 (s, 3 H); 1.33 (s, 3 H). 13C-NMR (125 MHz, CDCl3): 201.8; 154.3; 147.1; 138.0; 137.3;
129.3 (2ꢁ); 126.5 (2ꢁ); 100.6; 100.5; 82.2; 78.6; 69.5; 60.4; 49.4; 48.5; 21.1; 18.9; 18.7. MS: 347 (3, [M ꢀ
MeO]þ). HR-MS: 401.1576 ([M þ Na]þ, C20H26NaOþ7 ; calc. 401.1576).
(4S,5R,7R,8R)-2-[(S)-(2-Chlorophenyl)(hydroxy)methyl]-4-hydroxy-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (4fA). Less polar. Yield: 30.0 mg (38%). White solid. M.p. 153 – 1548.
[a]2D5 ¼ þ17.4 (c ¼ 1.27, CHCl3). IR (KBr): 3279, 1718, 1444, 1214, 1160, 1100, 1038. 1H-NMR (300 MHz,
CDCl3): 7.57 (dd, J ¼ 7.5, 1.6, 1 H); 7.38 – 7.24 (m, 3 H); 7.02 (s, 1 H); 5.92 (s, 1 H); 4.88 (s, 1 H); 4.16 (d,
J ¼ 11.0, 1 H); 3.89 (d, J ¼ 11.0, 1 H); 3.48 (s, 3 H); 3.42 (s, 3 H); 3.54 – 3.31 (br., 2 OH); 1.44 (s, 3 H); 1.36
(s, 3 H). 13C-NMR (75 MHz, CDCl3): 202.1; 155.4; 145.0; 137.5; 132.2; 129.6; 129.2; 127.8; 127.2; 100.6;

Helvetica Chimica Acta – Vol. 95 (2012)
1921
100.5; 82.6; 78.5; 65.9;60.3; 49.3; 48.6; 18.8; 18.7. MS: 399 (0.2, [M þ 1]þ). HR-MS: 421.1036 ([M þ Na]þ,
C19H23ClNaOþ7 ; calc. 421.1030).
(4S,5R,7R,8R)-2-[(R)-(2-Chlorophenyl)(hydroxy)methyl]-4-hydroxy-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (4fB). More polar. Yield: 25.2 mg (32%). White solid. M.p. 160 – 1618.
1
[a]2D5 ¼ ꢀ96.6 (c ¼ 1.08, CHCl3). IR (KBr): 3400, 1717, 1147, 1109, 1039. H-NMR (300 MHz, CDCl3):
7.57 (dd, J ¼ 7.5, 1.7, 1 H); 7.39 – 7.04 (m, 3 H); 6.97 (dd, J ¼ 2.0; 1.4, 1 H); 5.93 (s, 1 H); 4.89 (d, J ¼ 1.8,
1 H); 4.16 (d, J ¼ 11.1, 1 H); 3.88 (d, J ¼ 11.1, 1 H); 3.46 (s, 3 H); 3.52 – 3.38 (br., OH); 3.42 (s, 3 H);
3.38 – 3.30 (br., OH); 1.44 (s, 3 H); 1.36 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 202.2; 155.3; 145.2; 137.7;
132.3; 129.5; 129.2; 128.2; 127.3; 100.7 (2ꢁ); 82.2; 78.4; 66.3; 60.3; 49.3; 48.6; 18.9; 18.7. MS: 398 (0.5,
Mþ), 367 (2, [M ꢀ MeO]þ). HR-MS: 421.1044 ([M þ Na]þ, C19H23ClNaOþ7 ; calc. 421.1030).
(4S,5R,7R,8R)-4-Hydroxy-2-[(S)-hydroxy(4-methoxyphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (4gA). Less polar. Yield: 17.9 mg (23%). White solid. M.p. 155 – 1568.
[a]2D5 ¼ þ2.8 (c ¼ 0.67, CHCl3). IR (KBr): 3491, 3386, 1692, 1461, 1217, 1146, 1055. 1H-NMR (300 MHz,
CDCl3): 7.28 (d, J ¼ 8.7, 2 H); 7.20 (dd, J ¼ 1.8, 1.6, 1 H); 6.89 (d, J ¼ 8.7, 2 H); 5.48 (s, 1 H); 4.91 (d, J ¼
2.2, 1 H); 4.09 (d, J ¼ 10.9, 1 H); 3.81 (s, 3 H); 3.80 (d, J ¼ 10.9, 1 H); 3.48 (s, 3 H); 3.43 (s, 3 H); 3.37 (d,
J ¼ 2.8, 1 H); 2.88 (d, J ¼ 3.1, 1 H); 1.43 (s, 3 H);1.36 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 201.7; 159.6;
154.0; 147.3; 132.5; 127.9 (2ꢁ); 114.1 (2ꢁ); 100.7; 100.6; 82.7; 78.5; 69.3; 60.3; 55.3; 49.4; 48.6; 18.9; 18.7.
MS: 395 (0.7, [M þ 1]þ), 363 (8, [M ꢀ MeO]þ). HR-MS: 417.1508 ([M þ Na]þ, C20H26NaOþ8 ; calc.
417.1525).
(4S,5R,7R,8R)-4-Hydroxy-2-[(R)-hydroxy(4-methoxyphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (4gB). More polar. Yield: 6.7 mg (9%). White solid. M.p. 174 – 1758.
[a]2D5 ¼ ꢀ32.4 (c ¼ 0.73, CHCl3). IR (KBr): 3392, 1720, 1611, 1510, 1248, 1036. 1H-NMR (500 MHz,
CDCl3): 7.31 (d, J ¼ 8.7, 2 H); 7.20 (dd, J ¼ 2.2, 1.3, 1 H); 6.90 (d, J ¼ 8.7, 2 H); 5.48 (s, 1 H); 4.89 (d, J ¼ 1.7,
1 H); 4.18 (d, J ¼ 11.0, 1 H); 3.90 (d, J ¼ 11.0, 1 H); 3.82 (s, 3 H); 3.44 (s, 3 H); 3.40 (s, 3 H); 3.29 (d, J ¼
2.9, 1 H); 2.88 – 2.82 (br., OH); 1.44 (s, 3 H); 1.34 (s, 3 H). 13C-NMR (125 MHz, CDCl3): 201.8; 159.5;
154.1; 147.2; 132.4; 127.9 (2ꢁ); 114.1 (2ꢁ); 100.6; 100.5; 82.2; 78.6; 69.3; 60.4; 55.3; 49.4; 48.5; 18.9; 18.7.
MS: 394 (3, Mþ). HR-MS: 417.1516 ([M þ Na]þ, C20H26NaOþ8 ; calc. 417.1525).
(4S,5R,7R,8R)-2-[(R)-(Furan-2-yl)(hydroxy)methyl]-4-hydroxy-7,8-dimethoxy-7,8-dimethyl-6,9-di-
oxaspiro[4.5]dec-2-en-1-one (4hA). Less polar. Yield: 15.8 mg (23%). White solid. M.p. 133 – 1348.
[a]2D5 ¼ ꢀ23.8 (c ¼ 0.57, CHCl3). IR (KBr): 3389, 3261, 1723, 1640, 1499, 1212, 1041. 1H-NMR (300 MHz,
CDCl3): 7.46 – 7.34 (m, 2 H); 6.35 (dd, J ¼ 3.2, 1.9, 1 H); 6.28 (d, J ¼ 3.2, 1 H); 5.58 (s, 1 H); 4.95 (d, J ¼ 1.9,
1 H); 4.17 (d, J ¼ 10.9, 1 H); 3.89 (d, J ¼ 10.9, 1 H); 3.49 (s, 3 H); 3.45 (s, 3 H); 3.42 (d, J ¼ 2.6, 1 H);
3.07 – 2.98 (br., OH); 1.44 (s, 3 H); 1.37 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 201.3; 155.2; 152.7; 144.3;
142.8; 110.5; 107.9; 100.7; 100.6; 82.6; 78.6; 63.3; 60.4; 49.4; 48.6; 18.9; 18.7. MS: 354 (23, Mþ). HR-MS:
377.1212 ([M þ Na]þ, C17H22NaOþ8 ; calc. 377.1212).
(4S,5R,7R,8R)-2-[(S)-(Furan-2-yl)(hydroxy)methyl]-4-hydroxy-7,8-dimethoxy-7,8-dimethyl-6,9-di-
oxaspiro[4.5]dec-2-en-1-one (4hB). More polar. Yield: 24.9 mg (35%). White solid. M.p. 142 – 1438.
[a]2D5 ¼ ꢀ33.4 (c ¼ 0.54, CHCl3). IR (KBr): 3427, 1709, 1639, 1459, 1146, 1110, 1036. 1H-NMR (300 MHz,
CDCl3): 7.40 – 7.38 (m, 2 H); 6.38 – 6.33 (m, 1 H); 6.30 (d, J ¼ 3.2, 1 H); 5.55 (s, 1 H); 4.94 (s, 1 H); 4.19 (d,
J ¼ 11.0, 1 H); 3.92 (d, J ¼ 11.0, 1 H); 3.44 (s, 3 H); 3.48 – 3.31 (br., OH); 3.42 (s, 3 H); 3.25 – 3.05 (br.,
OH); 1.44 (s, 3 H); 1.35 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 201.5; 155.3; 152.7; 144.1; 142.8; 110.5;
107.9; 100.6 (2ꢁ); 82.1; 78.6; 63.4; 60.3; 49.4; 48.5; 18.9; 18.7. MS: 354 (14, Mþ). HR-MS: 377.1210 ([M þ
Na]þ, C17H22NaOþ8 ; calc. 377.1212).
(4S,5R,7R,8R)-2-[(S)-(2,3-Dimethoxyphenyl)(hydroxy)methyl]-4-hydroxy-7,8-dimethoxy-7,8-di-
methyl-6,9-dioxaspiro[4.5]dec-2-en-1-one (4iA). Less polar. Yield: 48.6 mg (57%). White solid. M.p.
174 – 1768. [a]2D5 ¼ þ7.0 (c ¼ 0.75, CHCl3). IR (KBr): 3380, 3275, 1715, 1485, 1294, 1040. 1H-NMR
(300 MHz, CDCl3): 7.24 (s, 1 H); 7.06 (t, J ¼ 7.9, 1 H); 6.90 (t, J ¼ 7.9, 2 H); 5.78 (s, 1 H); 4.91 (s, 1 H); 4.12
(d, J ¼ 10.8, 1 H); 3.88 (s, 6 H); 3.85 (d, J ¼ 10.8, 1 H); 3.48 (s, 3 H); 3.43 (s, 3 H); 3.42 – 3.30 (br., 2 OH);
1.43 (s, 3 H); 1.35 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 201.5; 154.5; 152.6; 146.8; 146.4; 133.9; 124.2;
119.4; 112.5; 100.6; 100.5; 82.6; 78.5; 65.3; 60.9; 60.4; 55.8; 49.3; 48.6; 18.9; 18.7. MS: 424 (0.7, Mþ), 393 (5,
[M ꢀ MeO] þ). HR-MS: 447.1613 ([M þ Na]þ, C21H28NaOþ9 ; calc. 447.1631).
(4S,5R,7R,8R)-2-[(R)-(2,3-Dimethoxyphenyl)(hydroxy)methyl]-4-hydroxy-7,8-dimethoxy-7,8-di-
methyl-6,9-dioxaspiro[4.5]dec-2-en-1-one (4iB). More polar. Yield: 6.5 mg (8%). White solid. M.p. 186 –

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Helvetica Chimica Acta – Vol. 95 (2012)
1878. [a]2D5 ¼ ꢀ55.0 (c ¼ 0.66, CHCl3). IR (KBr): 3461, 2927, 1717, 1636, 1482, 1285, 1114. 1H-NMR
(300 MHz, CDCl3): 7.16 (dd, J ¼ 2.1, 1.5, 1 H); 7.08 (t, J ¼ 7.9, 1 H); 6.96 (dd, J ¼ 7.9, 1.5, 1 H); 6.90 (dd,
J ¼ 8.1, 1.5, 1 H); 5.77 (d, J ¼ 5.2, 1 H); 4.88 (m, 1 H); 4.17 (d, J ¼ 10.8, 1 H); 3.90 (d, J ¼ 10.8, 1 H); 3.89
(s, 3 H); 3.87 (s, 3 H); 3.45 (s, 1 H); 3.43 (s, 3 H); 3.40 (s, 3 H); 3.12 (d, J ¼ 3.1, 1 H); 1.43 (s, 3 H); 1.34 (s,
3 H). 13C-NMR (75 MHz, CDCl3): 201.8; 154.5; 152.5; 146.7; 146.4; 133.7; 124.3; 119.6; 112.4; 100.5
(2ꢁ); 82.0; 78.5; 65.4; 60.9; 60.3; 55.8; 49.3; 48.5; 18.9; 18.7. MS: 424 (0.5, Mþ), 393 (1, [M ꢀ MeO]þ).
HR-MS: 447.1634 ([M þ Na]þ, C21H28NaO9þ ; calc. 447.1631).
(4S,5R,7R,8R)-4-Hydroxy-2-[(1S,2E)-1-hydroxy-3-phenylprop-2-en-1-yl]-7,8-dimethoxy-7,8-dimeth-
yl-6,9-dioxaspiro[4.5]dec-2-en-1-one (4jA). Less polar. Yield: 17.2 mg (21%). White solid. M.p. 163 –
1648. [a]2D5 ¼ ꢀ27.9 (c ¼ 0.59, CHCl3). IR (KBr): 3447, 1719, 1655, 1450, 1376, 1216, 1144, 1115, 1035.
1H-NMR (300 MHz, CDCl3): 7.41 ꢀ 7.29 (m, 6 H); 6.71 (d, J ¼ 15.9, 1 H); 6.28 (dd, J ¼ 15.9, 6.6, 1 H);
5.16 (d, J ¼ 6.6, 1 H); 4.94 (s, 1 H); 4.20 (d, J ¼ 10.9, 1 H); 3.89 (d, J ¼ 10.9, 1 H); 3.51 (s, 3 H); 3.46 (s,
3 H); 3.40 – 3.27 (br., OH); 2.96 – 2.60 (br., OH); 1.45 (s, 3 H); 1.37 (s, 3 H). 13C-NMR (75 MHz, CDCl3):
201.9; 154.2; 145.9; 136.1; 132.2; 128.6 (2ꢁ); 128.1; 127.5; 126.7 (2ꢁ); 100.7; 100.6; 82.4; 78.7; 68.2; 60.4;
49.4; 48.6; 18.9; 18.8. MS: (0.5, [M þ 1]þ). HR-MS: 413.1578 ([M þ Na]þ, C21H26NaOþ7 ; calc. 413.1576).
(4S,5R,7R,8R)-4-Hydroxy-2-[(1R,2E)-1-hydroxy-3-phenylprop-2-en-1-yl]-7,8-dimethoxy-7,8-di-
methyl-6,9-dioxaspiro[4.5]dec-2-en-1-one (4jB). More polar. Yield: 16.2 mg (21%). White solid. M.p.
182 – 1838. [a]2D5 ¼ ꢀ33.6 (c ¼ 0.71, CHCl3). IR (KBr): 3490, 1718, 1451, 1375, 1245, 1166, 1106, 1054.
1H-NMR (300 MHz, CDCl3): 7.41 – 7.27 (m, 6 H); 6.71 (d, J ¼ 15.9, 1 H); 6.29 (dd, J ¼ 15.9, 6.5, 1 H); 5.14
(d, J ¼ 6.5, 1 H); 4.93 (s, 1 H); 4.20 (d, J ¼ 11.0, 1 H); 3.91 (d, J ¼ 11.0, 1 H); 3.47 (s, 3 H); 3.45 (s, 3 H);
1.45 (s, 3 H); 1.36 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 201.8; 154.2; 146.1; 136.5; 132.1; 128.6 (2ꢁ);
128.0; 126.8 (2ꢁ); 100.8 (2ꢁ); 82.2; 78.8; 68.3; 60.4; 49.3; 48.6; 18.9; 18.7. MS: 390 (7, Mþ). HR-MS:
413.1575 ([M þ Na]þ, C21H26NaOþ7 ; calc. 413.1576).
(4S,5R,7R,8R)-4-Hydroxy-2-[(1S)-1-hydroxypropyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxaspiro[4.5]-
dec-2-en-1-one (4kA). Less polar. Yield: 23.4 mg (37%). White solid. M.p. 121 – 1228. [a]2D5 ¼ ꢀ46.4 (c ¼
0.89, CHCl3). IR (KBr): 3472, 3383, 1697, 1465, 1218, 1052. 1H-NMR (300 MHz, CDCl3): 7.28 (dd, J ¼ 2.3,
1.4, 1 H); 4.90 (d, J ¼ 1.8, 1 H); 4.44 – 4.34 (br., 1 H); 4.17 (d, J ¼ 10.9, 1 H); 3.86 (d, J ¼ 10.9, 1 H); 3.51 (s,
3 H); 3.45 (s, 3 H); 3.41 (d, J ¼ 2.4, 1 H); 2.60 – 2.40 (br., OH); 1.79 – 1.61 (m, 2 H); 1.44 (s, 3 H); 1.36 (s,
3 H); 0.95 (t, J ¼ 7.4, 3 H). 13C-NMR (75 MHz, CDCl3): 202.2; 153.7; 147.3; 100.7; 100.6; 82.5; 78.5; 68.5;
60.5; 49.4; 48.6; 28.4; 18.9; 18.8; 9.5. MS: 316 (0.2, Mþ). HR-MS: 339.1405 ([M þ Na]þ, C15H24NaO7þ ;
calc. 339.1420).
(4S,5R,7R,8R)-4-Hydroxy-2-[(1R)-1-hydroxypropyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxaspiro[4.5]-
dec-2-en-1-one (4kB). More polar. Yield: 22.7 mg (36%). White solid. M.p. 133 – 1348. [a]2D5 ¼ ꢀ13.5 (c ¼
1
0.85, CHCl3). IR (KBr): 3504, 1717, 1381, 1219, 1162, 1105, 1047. H-NMR (300 MHz, CDCl3): 7.28 (d,
J ¼ 2.0, 1 H); 4.90 (dd, J ¼ 3.4, 2.0, 1 H); 4.39 – 4.35 (m, 1 H); 4.17 (d, J ¼ 11.0, 1 H); 3.87 (d, J ¼ 11.0,
1 H); 3.48 (s, 3 H); 3.44 (s, 3 H); 2.92 – 2.20 (br., 2 OH); 1.84 – 1.55 (m, 2 H); 1.44 (s, 3 H); 1.36 (s, 3 H);
0.97 (t, J ¼ 7.4, 3 H). 13C-NMR (75 MHz, CDCl3): 202.2; 153.9; 147.2; 100.6 (2ꢁ); 82.2; 78.6; 68.6; 60.4;
49.4; 48.5; 28.4; 18.9; 18.7; 9.5. MS: 317 (8, [M þ 1]þ), 285 (19, [M ꢀ MeO]þ). HR-MS: 339.1415 ([M þ
Na]þ, C15H24NaOþ7 ; calc. 339.1420).
(4S,5R,7R,8R)-4-Hydroxy-2-[(1S)-1-hydroxy-2-methylpropyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxa-
spiro[4.5]dec-2-en-1-one (4lA). Less polar. Yield: 22.3 mg (34%). White solid. M.p. 139 – 1408. [a]D25
¼
ꢀ44.2 (c ¼ 0.85, CHCl3). IR (KBr): 3491, 3386, 1692, 1640, 1461, 1299, 1217, 1145, 1104, 1055.
1H-NMR (300 MHz, CDCl3): 7.28 (s, 1 H); 4.91 (s, 1 H); 4.25 (d, J ¼ 5.1, 1 H); 4.18 (d, J ¼ 10.9, 1 H); 3.87
(d, J ¼ 10.9, 1 H); 3.52 (s, 3 H); 3.45 (s, 3 H); 2.46 – 2.23 (br., OH); 2.06 – 1.87 (m, 1 H); 1.86 – 1.68 (br.,
OH); 1.45 (s, 3 H); 1.37 (s, 3 H); 0.93 (d, J ¼ 6.8, 3 H); 0.89 (d, J ¼ 6.8, 3 H). 13C-NMR (75 MHz, CDCl3):
201.9; 154.6; 146.5; 100.6; 100.5; 82.7; 78.4; 72.2; 60.5; 49.3; 48.5; 32.4; 18.9; 18.8; 18.7; 16.6. MS: 330 (0.5,
Mþ), 299 (3, [M ꢀ MeO]þ). HR-MS: 353.1567 ([M þ Na]þ, C16H26NaOþ7 ; calc. 353.1576).
(4S,5R,7R,8R)-4-Hydroxy-2-[(1R)-1-hydroxy-2-methylpropyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxa-
spiro[4.5]dec-2-en-1-one (4lB). More polar. Yield: 6.9 mg (10%). White solid. M.p. 149 – 1518. [a]D25
¼
þ5.8 (c ¼ 0.51, CHCl3). IR (KBr): 3501, 3409, 1710, 1463, 1379, 1221, 1166, 1105, 1039. 1H-NMR
(300 MHz, CDCl3): 7.27 (dd, J ¼ 2.2, 1.0, 1 H); 4.94 (dd, J ¼ 2.1, 0.9, 1 H); 4.21 (d, J ¼ 10.8, 1 H); 4.20 (d,
J ¼ 5.6, 1 H); 3.87 (d, J ¼ 10.8, 1 H); 3.51 (s, 3 H); 3.46 (s, 3 H); 3.57 – 3.20 (br., OH); 2.70 – 2.20 (br.,
OH); 2.10 – 1.91 (m, 1 H); 1.45 (s, 3 H); 1.37 (s, 3 H); 0.93 (d, J ¼ 4.8, 3 H); 0.91 (d, J ¼ 4.7, 3 H).

Helvetica Chimica Acta – Vol. 95 (2012)
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13C-NMR (75 MHz, CDCl3): 202.4; 155.0; 146.2; 100.9; 100.8; 82.7; 78.8; 73.0; 60.6; 49.4; 48.6; 32.6; 19.0;
18.9; 18.8; 16.7. MS: 330 (6, Mþ), 299 (24, [M ꢀ MeO]þ). HR-MS: 353.1555 ([M þ Na]þ, C16H26NaOþ7 ;
calc. 353.1576).
(4S,5R,7R,8R)-4-Hydroxy-2-[(1S)-1-hydroxybutyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxaspiro[4.5]-
dec-2-en-1-one (4mA). Less polar. Yield: 25.3 mg (38%). White solid. M.p. 101 – 1028. [a]2D5 ¼ ꢀ55.3 (c ¼
0.98, CHCl3). IR (KBr): 3481, 3406, 1690, 1376, 1319, 1217, 1158, 1107, 1057. 1H-NMR (300 MHz, CDCl3):
7.27 (dd, J ¼ 2.2, 1.3, 1 H); 4.90 (s, 1 H); 4.46 (t, J ¼ 5.9, 1 H); 4.17 (d, J ¼ 10.9, 1 H); 3.86 (d, J ¼ 10.9,
1 H); 3.50 (s, 3 H); 3.45 (s, 3 H); 3.41 (s, 1 H); 2.61 – 2.36 (br., OH); 1.68 – 1.59 (m, 2 H); 1.50 – 1.33 (m,
2 H); 1.44 (s, 3 H); 1.36 (s, 3 H); 0.94 (t, J ¼ 7.3, 3 H). 13C-NMR (75 MHz, CDCl3): 202.2; 153.5; 147.7;
100.7; 100.6; 82.5; 78.5; 67.1; 60.5; 49.4; 48.6; 37.6; 18.9; 18.7; 18.5; 13.8. MS: 327 (10, [M ꢀ 3]þ), 299 (20,
[M ꢀ MeO]þ). HR-MS: 353.1589 ([M þ Na]þ, C16H26NaOþ7 ; calc. 353.1576).
(4S,5R,7R,8R)-4-Hydroxy-2-[(1R)-1-hydroxybutyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxaspiro[4.5]-
dec-2-en-1-one (4mB). More polar. Yield: 20.2 mg (31%). White solid. M.p. 127 – 1288. [a]2D5 ¼ ꢀ7.3 (c ¼
0.79, CHCl3). IR (KBr): 3412, 3358, 1725, 1429, 1377, 1256, 1108, 1044. 1H-NMR (300 MHz, CDCl3): 7.27
(dd, J ¼ 2.5, 1.2, 1 H); 4.91 (s, 1 H); 4.44 (dd, J ¼ 7.4, 4.3, 1 H); 4.19 (d, J ¼ 10.9, 1 H); 3.87 (d, J ¼ 10.9,
1 H); 3.50 (s, 3 H); 3.45 (s, 3 H); 3.37 (d, J ¼ 3.4, 1 H); 2.59 – 2.44 (br., OH); 1.76 – 1.35 (m, 4 H); 1.45 (s,
3 H); 1.37 (s, 3 H); 0.95 (t, J ¼ 7.3, 3 H). 13C-NMR (75 MHz, CDCl3): 202.2; 153.7; 147.5; 100.7; 100.6;
82.4; 78.6; 67.2; 60.5; 49.4; 48.6; 37.6; 18.9; 18.8; 18.5; 13.8. MS: 330 (0.5, Mþ), 299 (5, [M ꢀ MeO]þ). HR-
MS: 353.1566 ([M þ Na]þ, C16H26NaO7þ ; calc. 353.1576).
(4S,5R,7R,8R)-4-Hydroxy-2-[(1S)-1-hydroxy-3-phenylpropyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxa-
spiro[4.5]dec-2-en-1-one (4nA). Less polar. Yield: 17.0 mg (22%). White solid. M.p. 135 – 1378. [a]D25
¼
ꢀ41.8 (c ¼ 0.72, CHCl3). IR (KBr): 3470, 1713, 1456, 1377, 1220, 1144, 1108, 1034. 1H-NMR
(300 MHz, CDCl3): 7.32 – 7.18 (m, 6 H); 4.93 – 4.86 (m, 1 H); 4.45 – 4.42 (m, 1 H); 4.17 (d, J ¼ 10.9,
1 H); 3.85 (d, J ¼ 10.9, 1 H); 3.51 (s, 3 H); 3.45 (s, 3 H); 3.33 (d, J ¼ 2.6, 1 H); 2.88 – 2.67 (m, 2 H); 2.61 –
2.48 (br., OH); 2.09 – 1.90 (m, 2 H); 1.45 (s, 3 H); 1.37 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 202.3; 153.7;
147.3; 141.3; 128.5 (4ꢁ); 126.0; 100.7; 100.6; 82.4; 78.5; 66.7; 60.4; 49.4; 48.6; 36.8; 31.5; 18.9; 18.8. MS:
392 (1, Mþ), 361 (5, [M ꢀ MeO]þ). HR-MS: 415.1715 ([M þ Na]þ, C21H28NaOþ7 ; calc. 415.1733).
(4S,5R,7R,8R)-4-Hydroxy-2-[(1R)-1-hydroxy-3-phenylpropyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxa-
spiro[4.5]dec-2-en-1-one (4nB). More polar. Yield: 22.1 mg (28%). White solid. M.p. 154 – 1558. [a]D25
¼
1
ꢀ9.4 (c ¼ 0.80, CHCl3). IR (KBr): 3502, 1718, 1455, 1382, 1223, 1164, 1105, 1057. H-NMR (300 MHz,
CDCl3): 7.32 – 7.21 (m, 6 H); 4.93 – 4.86 (br., 1 H); 4.52 – 4.39 (m, 1 H); 4.18 (d, J ¼ 10.9, 1 H); 3.86 (d, J ¼
10.9, 1 H); 3.49 (s, 3 H); 3.45 (s, 3 H); 3.39 – 3.31 (br., OH); 2.89 – 2.67 (m, 2 H); 2.69 – 2.54 (br., OH);
2.13 – 1.88 (m, 2 H); 1.45 (s, 3 H); 1.36 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 202.1; 153.7; 147.1; 141.2;
128.4 (4ꢁ); 125.9; 100.6 (2ꢁ); 82.2; 78.5; 66.7; 60.3; 49.3; 48.5; 36.7; 31.5; 18.8; 18.6. MS: 392 (0.5, Mþ),
361 (6, [M ꢀ MeO]þ). HR-MS: 415.1722 ([M þ Na]þ, C21H28NaO7þ ; calc. 415.1733).
(4R,5R,7R,8R)-4-Hydroxy-2-[(R)-hydroxy(phenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxa-
spiro[4.5]dec-2-en-1-one (5aA). Less polar. Yield: 26.8 mg (37%). Colorless oil. [a]2D5 ¼ ꢀ24.5 (c ¼ 0.99,
1
CHCl3). IR (CHCl3): 3492, 1723, 1455, 1376, 1240, 1111, 1035. H-NMR (300 MHz, CDCl3): 7.39 – 7.28
(m, 6 H); 5.53 (s, 1 H); 4.56 (s, 1 H); 4.22 (d, J ¼ 11.0, 1 H); 4.00 (s, 1 H); 3.51 (s, 3 H); 3.38 (s, 3 H); 3.31
(d, J ¼ 11.0, 1 H); 3.15 – 3.00 (br., OH); 1.43 (s, 3 H); 1.40 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 202.3;
154.6; 147.9; 140.2; 128.6 (2ꢁ); 128.2; 126.4 (2ꢁ); 100.9; 100.0; 78.4; 72.2; 69.5; 63.6; 48.6; 48.0; 18.8; 18.7.
MS: 364 (0.5, Mþ). HR-MS: 387.1411 ([M þ Na]þ, C19H24NaOþ7 ; calc. 387.1420).
(4R,5R,7R,8R)-4-Hydroxy-2-[(S)-hydroxy(phenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-6,9-dioxa-
spiro[4.5]dec-2-en-1-one (5aB). More polar. Yield: 17.8 mg (24%). Colorless oil. [a]2D5 ¼ ꢀ74.5 (c ¼ 0.69,
1
CHCl3). IR (CHCl3): 3503, 1721, 1671, 1455, 1376, 1010. H-NMR (300 MHz, CDCl3): 7.39 – 7.25 (m,
6 H); 5.55 (s, 1 H); 4.53 (s, 1 H); 4.29 (d, J ¼ 11.0, 1 H); 3.92 (s, 1 H); 3.45 (d, J ¼ 11.0, 1 H); 3.41 (s, 3 H);
3.38 (s, 3 H); 3.08 – 2.90 (br., OH); 1.40 (s, 6 H). 13C-NMR (75 MHz, CDCl3): 202.4; 154.9; 147.6; 140.1;
128.6 (2ꢁ); 128.3; 126.6 (2ꢁ); 100.8; 99.9; 78.3; 72.2; 69.6; 63.4; 48.5; 48.1; 18.7; 18.6. MS: 364 (0.5, Mþ).
HR-MS: 387.1423 ([M þ Na]þ, C19H24NaO7þ ; calc. 387.1420).
(4R,5R,7R,8R)-4-Hydroxy-2-[(R)-hydroxy(4-nitrophenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-6,9-
dioxaspiro[4.5]dec-2-en-1-one (5bA). Less polar. Yield: 54.8 mg (67%). Pale yellow oil. [a]2D5 ¼ ꢀ29.8
(c ¼ 1.71, CHCl3). IR (CHCl3): 3425, 1723, 1608, 1524, 1463, 1349, 1110, 1035. 1H-NMR (500 MHz,
CDCl3): 8.18 (d, J ¼ 8.7, 2 H); 7.57 (d, J ¼ 8.7, 2 H); 7.46 (dd, J ¼ 3.0, 1.3, 1 H); 5.63 (d, J ¼ 3.0, 1 H); 4.56

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Helvetica Chimica Acta – Vol. 95 (2012)
(t, J ¼ 1.9, 1 H); 4.19 (d, J ¼ 11.0, 1 H); 4.13 (d, J ¼ 1.9, 1 H); 3.99 (d, J ¼ 4.3, 1 H); 3.51 (s, 3 H); 3.36 (s,
3 H); 3.25 (d, J ¼ 11.0, 1 H); 1.39 (s, 3 H); 1.38 (s, 3 H). 13C-NMR (125 MHz, CDCl3): 202.0; 155.1; 147.7;
147.6; 147.4; 127.1 (2ꢁ); 123.7 (2ꢁ); 101.0; 100.1; 78.4; 72.3; 68.2; 63.4; 48.5; 48.0; 18.7; 18.6. MS: 409 (0.5,
Mþ), 378 (4, [M ꢀ MeO]þ). HR-MS: 432.1263 ([M þ Na]þ, C19H23NNaO9þ ; calc. 432.1271).
(4R,5R,7R,8R)-4-Hydroxy-2-[(S)-hydroxy(4-nitrophenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-6,9-
dioxaspiro[4.5]dec-2-en-1-one (5bB). More polar. Yield: 18.4 mg (22%). Pale yellow oil. [a]2D5 ¼ ꢀ60.1
1
(c ¼ 0.75, CHCl3). IR (CHCl3): 3499, 1723, 1607, 1526, 1350, 1110, 1035. H-NMR (500 MHz, CDCl3):
8.23 (d, J ¼ 8.6, 2 H); 7.61 (d, J ¼ 8.6, 2 H); 7.29 (dd, J ¼ 3.0, 1.4, 1 H); 5.66 (s, 1 H); 4.56 (t, J ¼ 3.0, 1 H);
4.31 (d, J ¼ 11.0, 1 H); 3.99 (d, J ¼ 2.1, 1 H); 3.46 (s, 3 H); 3.42 (d, J ¼ 11.0, 1 H); 3.38 (s, 3 H); 3.28 – 3.21
(br., OH); 1.41 (s, 6 H). 13C-NMR (125 MHz, CDCl3): 202.3; 155.6; 147.8; 147.1; 146.5; 127.4 (2ꢁ); 123.8
(2ꢁ); 101.0; 100.0; 78.3; 72.3; 68.6; 63.5; 48.5; 48.1; 18.7; 18.6. MS: 409 (0.3, Mþ), 378 (1, [M ꢀ MeO]þ).
HR-MS: 432.1246 ([M þ Na]þ, C19H23NNaO9þ ; calc. 432.1271).
(4R,5R,7R,8R)-2-[(R)-(4-Chlorophenyl)(hydroxy)methyl]-4-hydroxy-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (5cA). Less polar. Yield: 32.9 mg (41%). Colorless oil. [a]2D5 ¼ ꢀ23.8
1
(c ¼ 1.12, CHCl3). IR (CHCl3): 3441, 1723, 1492, 1377, 1111, 1035. H-NMR (300 MHz, CDCl3): 7.38 (s,
1 H); 7.35 – 7.23 (m, 4 H); 5.50 (s, 1 H); 4.55 (s, 1 H); 4.22 (d, J ¼ 11.0, 1 H); 4.03 (s, 1 H); 3.52 (s, 3 H);
3.37 (s, 3 H); 3.26 (d, J ¼ 11.0, 1 H); 3.33 – 3.15 (br., OH); 1.42 (s, 3 H); 1.40 (s, 3 H). 13C-NMR (75 MHz,
CDCl3): 202.3; 154.7; 147.7; 138.8; 133.9; 128.8 (2ꢁ); 127.8 (2ꢁ); 100.9; 100.0; 78.4; 72.3; 68.8; 63.6; 48.6;
48.0; 18.7; 18.6. MS: 398 (0.4, Mþ). HR-MS: 421.1010 ([M þ Na]þ, C19H23ClNaOþ7 ; calc. 421.1030).
(4R,5R,7R,8R)-2-[(S)-(4-Chlorophenyl)(hydroxy)methyl]-4-hydroxy-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (5cB). More polar. Yield: 21.5 mg (27%). Colorless oil. [a]2D5 ¼ ꢀ69.0
(c ¼ 0.95, CHCl3). IR (CHCl3): 3499, 1722, 1492, 1377, 1110, 1035. 1H-NMR (300 MHz, CDCl3): 7.34 (s,
4 H); 7.26 (dd, J ¼ 2.8, 1.3, 1 H); 5.52 (s, 1 H); 4.53 (s, 1 H); 4.29 (d, J ¼ 11.0, 1 H); 3.94 (s, 1 H); 3.44 (s,
3 H); 3.43 (d, J ¼ 11.0, 1 H); 3.38 (s, 3 H); 3.04 – 2.92 (br., OH); 1.41 (s, 6 H). 13C-NMR (75 MHz,
CDCl3): 202.4; 155.1; 147.2; 138.6; 134.0; 128.8 (2ꢁ); 128.0 (2ꢁ); 100.9; 99.9; 78.3; 72.2; 68.9; 63.5; 48.5;
48.1; 18.7; 18.6. MS: 398 (1, Mþ). HR-MS: 421.1012 ([M þ Na]þ, C19H23ClNaOþ7 ; calc. 421.1030).
(4R,5R,7R,8R)-4-Hydroxy-2-[(R)-hydroxy(3-methoxyphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (5dA). Less polar. Yield: 41.2 mg (52%). Colorless oil. [a]2D5 ¼ ꢀ28.1
(c ¼ 1.74, CHCl3). IR (CHCl3): 3496, 1724, 1602, 1465, 1376, 1260, 1111, 1035. 1H-NMR (300 MHz,
CDCl3): 7.38 (s, 1 H); 7.24 (d, J ¼ 8.1, 1 H); 6.93 (s, 2 H); 6.83 (d, J ¼ 8.1, 1 H); 5.50 (s, 1 H); 4.55 (s, 1 H);
4.22 (d, J ¼ 11.0, 1 H); 3.80 (s, 3 H); 3.51 (s, 3 H); 3.37 (s, 3 H); 3.32 (d, J ¼ 11.0, 1 H); 1.42 (s, 3 H); 1.40 (s,
3 H). 13C-NMR (75 MHz, CDCl3): 202.3; 159.8; 154.7; 147.8; 141.9; 129.6; 118.7; 113.7; 111.8; 100.9;
100.0; 78.4; 72.2; 69.3; 63.5; 55.2; 48.6; 48.0; 18.7; 18.6. MS: 394 (3, Mþ). HR-MS: 417.1527 ([M þ Na]þ,
C20H26NaOþ8 ; calc. 417.1525).
(4R,5R,7R,8R)-4-Hydroxy-2-[(S)-hydroxy(3-methoxyphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (5dB). More polar. Yield: 7.0 mg (9%). Colorless oil. [a]2D5 ¼ ꢀ75.5
(c ¼ 1.70, CHCl3). IR (CHCl3): 3499, 1721, 1601, 1490, 1465, 1376, 1260, 1036. 1H-NMR (300 MHz,
CDCl3): 7.33 – 7.19 (m, 2 H); 7.00 – 6.90 (m, 2 H); 6.89 – 6.80 (m, 1 H); 5.53 (s, 1 H); 4.52 (s, 1 H); 4.29 (d,
J ¼ 11.0, 1 H); 3.92 (s, 1 H); 3.82 (s, 3 H); 3.45 (d, J ¼ 11.0, 1 H); 3.42 (s, 3 H); 3.38 (s, 3 H); 3.12 – 2.92
(br., OH); 1.41 (s, 6 H). 13C-NMR (75 MHz, CDCl3): 202.5; 159.8; 155.1; 147.4; 141.6; 129.7; 118.9; 113.9;
112.0; 100.9; 99.9; 78.3; 72.2; 69.4; 63.4; 55.2; 48.5; 48.1; 18.7; 18.6. MS: 395 (1, [M þ 1]þ), 363 (4, [M ꢀ
MeO]þ). HR-MS: 417.1513 ([M þ Na]þ, C20H26NaOþ8 ; calc. 417.1525).
(4R,5R,7R,8R)-4-Hydroxy-2-[(R)-hydroxy(4-methylphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (5eA). Less polar. Yield: 34.9 mg (46%). Colorless oil. [a]2D5 ¼ ꢀ23.1
1
(c ¼ 1.56, CHCl3). IR (CHCl3): 3491, 1724, 1462, 1376, 1242, 1111, 1035. H-NMR (300 MHz, CDCl3):
7.41 (s, 1 H); 7.23 (d, J ¼ 8.0, 2 H); 7.15 (d, J ¼ 8.0, 2 H); 5.48 (s, 1 H); 4.56 (s, 1 H); 4.21 (d, J ¼ 11.0, 1 H);
4.00 (s, 1 H); 3.52 (s, 3 H); 3.38 (s, 3 H); 3.30 (d, J ¼ 11.0, 1 H); 3.11 – 2.89 (br., OH); 2.34 (s, 3 H); 1.43 (s,
3 H); 1.39 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 202.3; 154.3; 148.1; 137.9; 137.3; 129.3 (2ꢁ); 126.4 (2ꢁ);
100.9; 100.0; 78.5; 72.2; 69.4; 63.6; 48.6; 48.0; 21.1; 18.8; 18.7. MS: 347 (5, [M ꢀ MeO]þ). HR-MS:
401.1561 ([M þ Na]þ, C20H26NaOþ7 ; calc. 401.1576).
(4R,5R,7R,8R)-4-Hydroxy-2-[(S)-hydroxy(4-methylphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (5eB). More polar. Yield: 9.3 mg (12%). Colorless oil. [a]2D5 ¼ ꢀ64.1
1
(c ¼ 0.84, CHCl3). IR (CHCl3): 3508, 1722, 1462, 1377, 1111, 1035. H-NMR (300 MHz, CDCl3): 7.31 –

Helvetica Chimica Acta – Vol. 95 (2012)
1925
7.23 (m, 3 H); 7.18 (d, J ¼ 7.8, 2 H); 5.52 (s, 1 H); 4.56 – 4.50 (br., 1 H); 4.30 (d, J ¼ 11.0, 1 H); 3.91 (d, J ¼
2.2, 1 H); 3.45 (d, J ¼ 11.0, 1 H); 3.44 (s, 3 H); 3.38 (s, 3 H); 2.92 – 2.73 (br., OH); 2.36 (s, 3 H); 1.41 (s,
6 H). 13C-NMR (75 MHz, CDCl3): 202.5; 154.9; 147.7; 138.0; 137.1; 129.3 (2ꢁ); 126.6 (2ꢁ); 100.9; 99.9;
78.3; 72.2; 69.5; 63.6; 48.5; 48.1; 21.1; 18.7; 18.6. MS: 378 (0.5, Mþ), 347 (8, [M ꢀ MeO]þ). HR-MS:
401.1575 ([M þ Na]þ, C20H26NaOþ7 ; calc. 401.1576).
(4R,5R,7R,8R)-4-Hydroxy-2-[(R)-hydroxy(4-methoxyphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (5gA). Less polar. Yield: 35.9 mg (46%). Colorless oil. [a]2D5 ¼ ꢀ18.2
(c ¼ 1.33, CHCl3). IR (CHCl3): 3493, 1724, 1612, 1513, 1464, 1376, 1250, 1111, 1035. 1H-NMR (300 MHz,
CDCl3): 7.40 (dd, J ¼ 2.7, 1.3, 1 H); 7.27 (d, J ¼ 8.6, 2 H); 6.87 (d, J ¼ 8.6, 2 H); 5.48 (s, 1 H); 4.57 (s, 1 H);
4.22 (d, J ¼ 11.0, 1 H); 3.99 (d, J ¼ 1.6, 1 H); 3.80 (s, 3 H); 3.52 (s, 3 H); 3.38 (s, 3 H); 3.30 (d, J ¼ 11.0,
1 H); 2.93 (s, 1 H); 1.43 (s, 3 H); 1.40 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 202.3; 159.5; 154.3; 148.1;
132.4; 127.8 (2ꢁ); 114.0 (2ꢁ); 100.9; 100.0; 78.5; 72.3; 69.3; 63.7; 55.2; 48.6; 48.0; 18.8; 18.7. MS: 393 (0.2,
[M ꢀ 1]þ). HR-MS: 417.1522 ([M þ Na]þ, C20H26NaOþ8 ; calc. 417.1525).
(4R,5R,7R,8R)-4-Hydroxy-2-[(S)-hydroxy(4-methoxyphenyl)methyl]-7,8-dimethoxy-7,8-dimethyl-
6,9-dioxaspiro[4.5]dec-2-en-1-one (5gB). More polar. Yield: 4.0 mg (5%). Colorless oil. [a]2D5 ¼ ꢀ67.7
(c ¼ 0.76, CHCl3). IR (CHCl3): 3503, 1721, 1613, 1514, 1464, 1251, 1111, 1035. 1H-NMR (300 MHz,
CDCl3): 7.36 – 7.25 (m, 3 H); 6.90 (d, J ¼ 8.7, 2 H); 5.50 (s, 1 H); 4.54 (s, 1 H); 4.30 (d, J ¼ 11.0, 1 H); 3.92
(s, 1 H); 3.82 (s, 3 H); 3.45 (d, J ¼ 11.0, 1 H); 3.43 (s, 3 H); 3.38 (s, 3 H); 2.91 – 2.76 (br., OH); 1.40 (s,
6 H). 13C-NMR (75 MHz, CDCl3): 202.4; 159.6; 154.7; 147.8; 132.3; 128.0 (2ꢁ); 114.1 (2ꢁ); 100.9; 99.9;
78.3; 72.2; 69.3; 63.5; 55.3; 48.5; 48.1; 18.7; 18.6. MS: 394 (0.3, Mþ). HR-MS: 417.1509 ([M þ Na]þ,
C20H26NaOþ8 ; calc. 417.1525).
Hydrolysis of 4aA with 1% aq. TFA. Compound 4aA (31.5 mg, 86.4 mmol) was treated with 1% aq.
TFA (0.5 ml) at r.t. After stirring for 5 h, the solvent was removed in vacuo, and the crude product was
purified by PLC (SiO2; 10% acetone/AcOEt (2ꢁ)).
(4R,5R)-4,5-Dihydroxy-5-(hydroxymethyl)-2-[(S)- and (R)-hydroxy(phenyl)methyl]cyclopent-2-
en-1-ones (6aA/6aB): Yield: 14.2 mg (66%). dr: 3.8 :1. Colorless oil. [a]2D5 ¼ þ77.7 (c ¼ 0.92, acetone).
IR (neat): 3376, 1711, 1621, 1367, 1051. 1H-NMR (500 MHz, (D6)acetone, 6aA marked*): 7.29 – 7.26 (m, 6
arom. H of 6aA and 6aB); 7.19 – 7.15 (m, 4 arom. H of 6aA and 6aB); 7.12 – 7.09 (m, 2 CH of 6aA and
6aB); 5.39 – 5.30 (m, 2 CH of 6aA and 6aB ); 4.88 (d, J ¼ 6.3, OH*); 4.86 (d, J ¼ 6.3, OH of 6aB); 4.69 (d,
J ¼ 4.6, OH of 6aB); 4.67 (d, J ¼ 4.6, OH*); 4.62 – 4.57 (m, 2 CH of 6aA and 6aB); 4.40 (s, OH*); 4.38 (s,
OH of 6aB); 3.53 – 3.47 (m, 2 CH2 of 6aA and 6aB); 3.43 (dd, J ¼ 6.8, 5.5, 2 OH of 6aA and 6aB).
13C-NMR (125 MHz, (D6)acetone, 6aA marked*): 205.2 (C¼O of 6aA and 6aB); 155.8 (CH of 6aB);
155.4 (CH*); 149.3 (C*); 149.2 (C of 6aB); 143.4 (C of 6aB); 143.2 (C*); 128.9 (2 ꢁ , CH of 6aA and
6aB); 128.2 (CH of 6aA and 6aB); 127.7 (2 ꢁ , CH*); 127.5 (2 ꢁ , CH of 6aB); 82.7 (C*); 82.3 (C of 6aB);
78.3 (CH of 6aB); 77.9 (CH*); 69.0 (CH of 6aA and 6aB); 65.5 (CH2 of 6aB); 65.4 (CH2*). MS: 251 (2,
[M þ 1]þ). HR-MS: 273.0759 ([M þ Na]þ, C13H14NaOþ5 ; calc. 273.0739).
Hydrolysis of 4 or 5 with 1% aq. TFA. Compound 4 or 5 was treated with 1% aq. TFA (0.5 ml) at r.t.
After water bath sonication (35 kHz, 120/480 W, 40 – 608) for 3 h, the solvent was removed in vacuo, and
the crude product was purified by PLC (SiO2; 10% acetone/AcOEt (2ꢁ)).
(4S,5R)-4,5-Dihydroxy-5-(hydroxymethyl)-2-[(S)-hydroxy(4-methylphenyl)methyl]cyclopent-2-en-
1-one (6eA). Hydrolysis of 4eA (27.3 mg, 72.1 mmol) gave 6eA 14.8 mg (78%). Colorless, viscous oil.
[a]2D5 ¼ þ78.3 (c ¼ 0.86, acetone). IR (neat): 3391, 1711, 1622, 1514, 1416, 1360, 1214, 1115, 1052.
1H-NMR (300 MHz, (D6)acetone): 7.39 (dd, J ¼ 2.2, 1.4, 1 H); 7.26 (d, J ¼ 8.0, 2 H); 7.09 (d, J ¼ 8.0, 2 H);
5.42 (s, 1 H); 5.02 (d, J ¼ 5.8, 1 H); 4.77 – 4.64 (m, 2 H); 4.51 (s, 1 H); 3.67 – 3.46 (m, 3 H); 2.67 (s, 3 H).
13C-NMR (75 MHz, (D6)acetone): 205.2; 155.1; 149.4; 140.2; 137.6; 129.5 (2ꢁ); 127.7 (2ꢁ); 82.7; 77.9;
68.9; 65.4; 21.0. MS: 276 (5, [M ꢀ 4]þ). HR-MS: 287.0897 ([M þ Na]þ, C14H16NaOþ5 ; calc. 287.0895).
(4S,5R)-2-[(S)-(2-Chlorophenyl)(hydroxy)methyl]-4,5-dihydroxy-5-(hydroxymethyl)cyclopent-2-
en-1-one (6fB). Hydrolysis of 4fB (26.5 mg, 66.4 mmol) gave 6fB 13.6 mg (72%). Colorless, viscous oil.
[a]2D5 ¼ þ28.9 (c ¼ 1.01, acetone). IR (KBr): 3378, 1697, 1629, 1397, 1281, 1269, 1129, 1057. 1H-NMR
(500 MHz, (D6)acetone): 7.56 (dd, J ¼ 7.6, 2.0, 1 H); 7.38 (dd, J ¼ 7.6, 1.5, 1 H); 7.33 (dt, J ¼ 7.6, 1.5, 1 H);
7.29 (dt, J ¼ 7.6, 2.0, 1 H); 7.18 (dd, J ¼ 2.0, 1.5, 1 H); 5.86 (d, J ¼ 3.8, 1 H); 5.06 – 4.92 (m, 1 H); 4.78 – 4.69
(br., 1 H); 4.55 (s, 1 H); 3.80 – 3.60 (m, 3 H). 13C-NMR (125 MHz, (D6)acetone): 204.8; 156.8; 147.6;

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Helvetica Chimica Acta – Vol. 95 (2012)
140.4; 133.3; 130.0; 129.8; 129.4; 127.9; 82.7; 77.9; 65.4; 65.3. MS: 283 (3, [M ꢀ 1]þ), 249 (2, [M ꢀ Cl]þ).
HR-MS: 307.0348 ([M þ Na]þ, C13H13ClNaO5þ ; calc. 307.0349).
(4R,5R)-4,5-Dihydroxy-2-[(R)-hydroxy(3-methoxyphenyl)methyl]-5-(hydroxymethyl)cyclopent-2-
enone (7dA). Hydrolysis of 5dA (43.4 mg, 110.0 mmol) gave 7dA 22.9 mg (74%). Colorless, viscous oil.
[a]2D5 ¼ þ82.4 (c ¼ 1.03, acetone). IR (neat): 3391, 1713, 1602, 1489, 1261, 1152, 1046. 1H-NMR
(300 MHz, (D6)acetone): 7.32 (dd, J ¼ 2.4, 1.3, 1 H); 7.06 (t, J ¼ 8.2, 1 H); 6.88 – 6.76 (m, 2 H); 6.65 (ddd,
J ¼ 8.2, 2.4, 0.9, 1 H); 5.33 (d, J ¼ 4.7, 1 H); 4.75 (d, J ¼ 6.4, 1 H); 4.70 (ddd, J ¼ 7.7, 2.4, 0.9, 1 H); 4.66 (d,
J ¼ 4.8, 1 H); 4.12 (s, 1 H); 3.82 (dd, J ¼ 6.4, 4.8, 1 H); 3.62 (s, 3 H); 3.48 (dd, J ¼ 10.5, 6.4, 1 H); 3.39 (dd,
J ¼ 10.5, 4.8, 1 H). 13C-NMR (75 MHz, (D6)acetone): 205.2; 160.6; 156.3; 149.7; 144.9; 129.9; 119.8;
113.7; 113.1; 77.2; 70.8; 69.0; 64.3; 55.4. MS: 244 (20, [M ꢀ 2 ꢀ OH (2ꢁ)]þ). HR-MS: 303.0836 ([M þ
Na]þ, C14H16NaOþ6 ; calc. 303.0845).
(4R,5R)-4,5-Dihydroxy-2-[(S)-hydroxy(3-methoxyphenyl)methyl]-5-(hydroxymethyl)cyclopent-2-
enone (7dB). Hydrolysis of 5dB (54.8 mg, 138.9 mmol) gave 7dB 24.8 mg (63%). White solid. M.p. 133 –
1348. [a]2D5 ¼ þ2.7 (c ¼ 0.94, acetone). IR (KBr): 3446, 3338, 3262, 1702, 1596, 1334, 1239, 1151, 1071,
1026. 1H-NMR (500 MHz, (D6)acetone): 7.45 (dd, J ¼ 2.6, 1.3, 1 H); 7.20 (t, J ¼ 8.0, 1 H); 7.01 – 6.92 (m,
2 H); 6.79 (ddd, J ¼ 8.0, 2.6, 0.8, 1 H); 5.43 (d, J ¼ 4.6, 1 H); 4.92 (d, J ¼ 6.6, 1 H); 4.87 – 4.78 (m, 2 H);
4.21 (s, 1 H); 4.05 (t, J ¼ 5.7, 1 H); 3.75 (s, 3 H); 3.70 (dd, J ¼ 10.6, 5.7, 1 H); 3.56 (dd, J ¼ 10.6, 4.6, 1 H).
13C-NMR (125 MHz, (D6)acetone): 204.6; 160.5; 155.9; 149.8; 144.9; 129.9; 119.7; 113.5; 113.2; 76.9; 70.5;
68.8; 63.9; 55.4. MS: 229 (10, [M ꢀ OH (3ꢁ)]þ). HR-MS: 303.0838 ([M þ Na]þ, C14H16NaOþ6 ; calc.
303.0845).
(4R,5R)-4,5-Dihydroxy-5-(hydroxymethyl)-2-[(R)-hydroxy(4-methylphenyl)methyl]cyclopent-2-
enone (7eA). Hydrolysis of 5eA (24.7 mg, 65.3 mmol) gave 7eA 8.4 mg (49%). White solid. M.p. 131 –
1328. [a]2D5 ¼ þ40.4 (c ¼ 0.96, acetone). IR (KBr): 3471, 3350, 3291, 1719, 1638, 1359, 1226, 1152, 1051.
1H-NMR (300 MHz, (D6)acetone): 7.44 (dd, J ¼ 2.4, 1.4, 1 H); 7.23 (d, J ¼ 8.0, 2 H); 7.07 (d, J ¼ 8.0, 2 H);
5.42 (d, J ¼ 4.6, 1 H); 4.87 (d, J ¼ 6.5, 1 H); 4.84 – 4.77 (m, 1 H); 4.69 (d, J ¼ 4.6, 1 H); 4.23 (s, 1 H); 3.91
(dd, J ¼ 6.3, 4.8, 1 H); 3.57 (dd, J ¼ 10.6, 6.3, 1 H); 3.49 (dd, J ¼ 10.6, 4.8, 1 H); 2.26 (s, 3 H). 13C-NMR
(75 MHz, (D6)acetone): 205.2; 155.9; 149.8; 140.3; 137.6; 129.5 (2ꢁ); 127.6 (2ꢁ); 77.1; 70.7; 69.0; 64.2;
21.0. MS: 276 (10, [M ꢀ 4]þ). HR-MS: 287.0899 ([M þ Na]þ, C14H16NaOþ5 ; calc. 287.0895).
Hydrolysis of 4aA by Using Dowex 50 W-X8 (Hþ Form). A soln. of 4aA (20 mg, 54.9 mmol) in
MeOH (0.5 ml) was treated with the Dowex 50 W-X8 (Hþ form; 20 mg) at r.t. After stirring for 24 h,
Dowex resin was removed, and the crude product was purified by PLC (SiO2; 10% acetone/AcOEt) to
give a 1:1 mixture of diastereoisomers of 8a.
(2R,3S,4R,5E)-5- and (2R,3S,4S,5E)-5-Benzylidene-2,3-dihydroxy-2-(hydroxymethyl)-4-methoxycy-
clopentanone (8aA/8aB). Yield: 12.1 mg (83%). White semi-solid. [a]2D5 ¼ þ54.7 (c ¼ 0.83, acetone). IR
(KBr): 3422, 1711, 1629, 1455, 1384, 1100, 1075, 1067. 1H-NMR (500 MHz, (D6)acetone): 7.38 – 7.25 (m,
12 H); 5.13 – 4.95 (br., 2 H), 4.98 (s, 1 H); 4.96 (s, 1 H); 4.75 (t, J ¼ 1.9, 1 H); 4.65 – 4.43 (br., 2 H); 3.72
(dd, J ¼ 14.3, 11.0, 2 H); 3.58 (dd, J ¼ 19.4, 11.0, 1 H); 3.26 (s, 3 H); 3.25 (s, 3 H). 13C-NMR (125 MHz,
(D6)acetone): 205.1; 204.9; 156.2; 155.7; 147.0; 146.9; 140.4; 140.1; 129.1 (2ꢁ); 129.0 (2ꢁ); 128.6 (2ꢁ);
128.3 (2ꢁ); 128.1 (2ꢁ); 82.6; 82.2; 78.4; 78.3; 78.2; 78.0; 65.5; 65.3; 56.9 (2ꢁ). MS: 213 (15, [M ꢀ
3 OH]þ. HR-MS: 287.0890 ([M þ Na]þ, C14H16NaOþ5 ; calc. 287.0895).
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Received August 7, 2012