Stereoselective total synthesis of dinemasone A by double intramolecular hetero-Michael addition (DIHMA)

Article abstract of DOI:10.1039/c2ob26396c

The first total synthesis of dinemasone A, a bioactive metabolite with a spiroketal moiety, is described. The main strategy for the construction of the spiroketal unit involves a double intramolecular hetero-Michael addition (DIHMA) of an ynone moiety. The thus obtained axial-equatorial mono anomeric spiroketal, on spiroepimerization with ZnBr₂, was converted into the requisite axial-axial double anomeric spiroketal. The ynone moiety with four stereocentres, was prepared from a chiral propargylic alcohol (C5-C11 fragment) and a dihydroxy aldehyde (C1-C4 fragment), which in turn were obtained from d-mannitol and crotyl alcohol respectively.

Full text of DOI:10.1039/c2ob26396c

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PAPER
Stereoselective total synthesis of dinemasone A by double intramolecular
hetero-Michael addition (DIHMA)†
Gangavaram V. M. Sharma,*a Gourishetty Srikanth*a and Pothula Purushotham Reddyb
Received 18th July 2012, Accepted 13th August 2012
DOI: 10.1039/c2ob26396c
The first total synthesis of dinemasone A, a bioactive metabolite with a spiroketal moiety, is described.
The main strategy for the construction of the spiroketal unit involves a double intramolecular hetero-
Michael addition (DIHMA) of an ynone moiety. The thus obtained axial–equatorial mono anomeric
spiroketal, on spiroepimerization with ZnBr2, was converted into the requisite axial–axial double
anomeric spiroketal. The ynone moiety with four stereocentres, was prepared from a chiral propargylic
alcohol (C5–C11 fragment) and a dihydroxy aldehyde (C1–C4 fragment), which in turn were obtained
from D-mannitol and crotyl alcohol respectively.
Introduction
Target oriented synthesis (TOS)1 of natural products is always a
very fascinating endeavour for synthetic organic chemists. The
complex structural features and interesting biological activities,2
3
combined with the need for determination of structure and
absolute stereochemistry, greatly demand TOS. A variety of
natural products contain a spiroketal moiety,4 and a wide range
Fig. 1 Structures of dinemasones.
of bioactive molecules isolated from nature are equipped with a
spiroketal substructure.5 Thus, the development of stereo-
violaceum and alga Chlorella fusca. Dinemasone A 1 is com-
controlled synthetic methods for the synthesis of spiroketals has
prised of five stereogenic centres embedded on a 5,5-spiroketal
become one of the most attractive fields, which has culminated
frame work, wherein the configuration at the anomeric C6
in diverse synthetic strategies.6 The main synthetic protocols6 for
carbon corresponds to the thermodynamically favoured diaxial
the construction of the spiroketals are: (a) acid catalysed dehy-
arrangement.
drative cyclization of dihydroxy ketone, (b) double intramole-
Most of the routes developed for the synthesis of spiroketals
cular hetero-Michael addition (DIHMA), (c) metal catalyzed
are based on acid catalyzed dehydrative cyclization of dihydroxy
regioselective oxy-functionalization of internal alkynols, (d)
ketones.6b,c Herein, we report the first synthesis of dinemasone
reductive decyanation and (e) intramolecular iodo-
A 1 by using a double intramolecular hetero-Michael addition
spiroketalization.
(DIHMA)6d,8 on ynone as the key step to construct the spiroketal
The dinemasone family7a comprises three metabolites, viz.
moiety. The spiroketal realized with ‘axial–equatorial’ arrange-
dinemasone A 1, dinemasone B 1a and dinemasone C 1b7b
ment was spiroepimerized to the target spiroketal with ‘diaxial’
(Fig. 1). These metabolites were isolated from the culture of
arrangement.
endophytic fungus Dinemasporium strigosum, which in turn
was isolated from the roots of Calystegia sepium by Krohn and
co-workers.7a
Results and discussion
Dinemasone A 1 has exhibited activity against the Gram-
positive bacterium, Bacillus megaterium, fungus Microbottryum
1. Retrosynthetic analysis
The retrosynthetic approach for the synthesis of 1 (Scheme 1)
envisioned the formation of the spiroketal moiety through an
aOrganic and Biomolecular Chemistry Division, Hyderabad-500 007,
India. E-mail: esmvee@iict.res.in
acid catalyzed one pot desilylation and spiroketalization via
DIHMA, on the linear ynone segment 2. In turn, ynone 2 was
planned to be assembled from fragments 3 and 4, which in turn
could be prepared from 5 and 6 respectively. Thus, the main
objectives would be: (a) to synthesize fragment 4 using Corey–
bNMR group, CSIR-Indian Institute of Chemical Technology,
Hyderabad-500 007, India
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c2ob26396c
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Scheme 1 Retrosynthetic analysis.
Scheme 2 Reagents and conditions: (a) (i) N,N-dimethylformamide dimethyl acetal, 55 °C, 3 h, (ii) Ac2O, 130 °C, 3 h; (b) CuCl2·2H2O, CH3CN,
0 °C to rt, 30 min; (c) Pd/C, EtOAc, H2, 4 h; (d) p-TsCl, Et3N, Bu2SnO, CH2Cl2, rt, 30 min; (e) LiAlH4, THF, 0 °C to rt, 30 min; (f) PhCH(OMe)2,
CH2Cl2, CSA, 0 °C to rt, 5 h: (g) TBDMS-Cl, imidazole, CH2Cl2, 0 °C to rt, 2 h; (h) DIBAL-H, CH2Cl2, −40 °C, 1 h; (i) Dess–Martin periodinane,
CH2Cl2, 0 °C to rt, 30 min; ( j) CBr4, PPh3, CH2Cl2, Et3N, 0 °C, 3 h; (k) n-BuLi, THF, −78 °C, 1 h.
Fuchs reaction, (b) to form the carbon framework via C–C bond
formation using the lithium acetylide of 4 and aldehyde 3 and
finally (c) spiroketalization and spiroepimerization.
furnished 14 (96%), which on regioselective reductive opening
of the benzylidene acetal with DIBAL-H afforded alcohol 15 in
90% yield. Oxidation of 15 with Dess–Martin periodinane13
gave the aldehyde 16 (chromatographically unstable), which was
subsequently treated with CBr4 and PPh3 to furnish dibromo-
olefin 17 (chromatographically unstable). Finally, the dibromo-
olefin 17 on treatment with n-BuLi gave the alkyne 4 in 80%
yield.14
2. Synthesis of alkyne 4
Alkyne 4 was synthesized from di-O-isopropylidene-D-mannitol
6 (Scheme 2). Accordingly, deoxygenation of the vicinal diol in
6, by adopting the procedure described by Eastwood and co-
workers,9 gave the corresponding olefin 7 in 88% yield.
Removal of acetonide using CuCl2·2H2O in acetonitrile10 furn-
ished the diol 8 in 54% yield, which on hydrogenation with
Pd/C afforded diol 9 (97%). A regioselective tosylation of the
primary hydroxyl group in 9 through dibutylstanylene acetal11
furnished 10, which on reduction with LiAlH4 gave alcohol 11
in 81% yield.12
3. Synthesis of aldehyde 3
Aldehyde 3 was synthesized from crotyl alcohol 5 in six steps
(Scheme 3). Accordingly, known alcohol 18,15 prepared from 5,
on Ti(OiPr)4 promoted regioselective opening of epoxide with
benzoic acid16 gave diol 1917 in 76% yield. Treatment of diol 19
with benzaldehyde dimethyl acetal and CSA (cat.) furnished the
benzylidene acetal 20 (82%), which on debenzoylation with
K2CO3 in methanol afforded alcohol 21 in 94% yield.
The carbinol 11 on treatment with CuCl2·2H2O in acetonitrile
at room temperature afforded triol 12 (82%), which on reaction
with benzaldehyde dimethyl acetal and CSA (cat.) gave 13 in
85% yield. Treatment of 13 with TBDMS-Cl and imidazole
Alcohol 21 was treated with TBDMS-Cl and imidazole to
give 22 (95%), which on regioselective reductive opening with
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DIBAL-H gave the alcohol 23 in 58% yield. The lower yield is
attributed to the concomitant formation of 23a. Finally, oxidation
of 23 with Dess–Martin periodinane in CH2Cl2 at room tempera-
ture furnished aldehyde 3.
Fig. 2b, is in agreement with the structure assigned from NMR
data.
The exclusive formation of 25 can be explained as follows
(Scheme 5). According to Baldwin’s rules18 for ring closure, the
6-endo-dig cyclization resulting in 2a, as shown in Path A, is
favourable over the 6-exo-dig process leading to 2b, as depicted
in path B. Furthermore, for the conversion of 2a to 26 through
27, it must experience steric hindrance between an axial hydro-
gen and a methyl group, while, for the transformation of 2a to
25 through 28, such steric congestion is avoided. It is thus poss-
ible that the cyclization would adopt path A, to give 25 as an
exclusive product from 2a. The reaction products thus are inde-
pendent of relative stabilities, but rather depend upon the relative
energy of transition states leading to them.
4. Synthesis of spiroketal precursor and spiroketalization
Alkyne 4 (Scheme 4) on reaction with n-BuLi followed by coup-
ling of the generated lithium acetylide with 3 afforded a mixture
of propargylic alcohols 24 (83%), which on oxidation with
Dess–Martin periodinane gave the ynone 2 in 90% yield. Desily-
lation of 2 on reaction with CSA (cat.) in MeOH and subsequent
treatment with p-TsOH in toluene at room temperature for 24 h
afforded the spiroketal 25 in 79% yield, under DIHMA
conditions.
The structure of the resultant spiroketal 25 was established on
the basis of extensive NMR analysis (Fig. 2). The newly formed
stereogenic centre at C6 in 25 was assigned from the character-
istic nOes observed between He5/H11, H2/H11, H2/Ha10 and
Ha10/Ha8 (Fig. 2a). The suggested ‘R’ configuration at the C6
anomeric centre of 25 thus corresponds to an ‘axial–equatorial’
arrangement. The energy minimized structure, as shown in
5. Epimerization of spiroketal 25 and synthesis of 1
Having successfully synthesized the spiroketal 25, the formation
of the desired ‘axial–axial’ spiroketal 26 was accomplished by
equilibration of the ‘axial–equatorial’ isomer 25 using Lewis
acid catalysis.19 The equilibration of spiro isomer 25 was studied
(Table 1) with various Lewis acids.
Finally, ZnBr2 was found to be the best compromise for selec-
tivity (∼1 : 1) for such equilibration in the present study,
wherein, unlike with other Lewis acids the conversion was 1 : 1
and 25 and 26 were in equilibrium with each other. Multidentate
Lewis acid might serve as a non covalent tether between the
keto- and anomeric oxygens of 25 and could activate the oxygen
to form an oxocarbonium ion intermediate, followed by the axial
attack of the oxygen on the oxocarbonium ion leading to 26.
nOe studies, in particular characteristic nOes observed
between H2/8-CH3, H11/5Ha and H11/5He (Scheme 6), unam-
biguously demonstrated that the diastereomer formed in equili-
brium conditions was the desired spiroketal 26 with ‘axial–axial’
Scheme 3 Reagents and conditions: (a) BzOH, Ti(OiPr)4, CH2Cl2,
0 °C to rt, 30 min; (b) benzaldehyde dimethyl acetal, CH2Cl2, CSA,
0 °C to rt, 5 h; (c) K2CO3, MeOH, rt, 30 min; (d) TBDMS-Cl, imida-
zole, CH2Cl2, 0 °C to rt, 2 h; (e) DIBAL-H, CH2Cl2, −40 °C, 1 h;
(f) Dess–Martin periodinane, CH2Cl2, 0 °C to rt, 30 min.
Fig. 2 (a) Observed nOes of 25; (b) energy minimized structure of 25.
Scheme 4 Reagents and conditions: (a) (i) n-BuLi, THF, −78 °C, 1 h; (ii) 3, THF, −78 °C, 1 h; (b) Dess–Martin periodinane, CH2Cl2, 0 °C to rt,
1 h; (c) (i) CSA, MeOH, rt, 2 h; (ii) PTSA, toluene, rt, 24 h.
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Scheme 5 Plausible concerted mechanism for the formation of 25.
purification. Column chromatographic separations were carried
out using silica gel (60–120 mesh). Organic solutions were dried
over anhydrous Na2SO4 and concentrated below 40 °C in vacuo.
1H NMR spectra (300 MHz, 500 MHz and 600 MHz), and 13C
NMR (75 MHz and 125 MHz) with TMS as internal standard
for solutions in CDCl3 were acquired on Bruker Avance
300 MHz, Innova 500 MHz and Bruker 600 MHz instruments.
J values are given in Hz. IR-spectra were recorded on FT IR
(Perkin-Elmer IR-683) spectrophotometer with NaCl optics.
JASCO DIP 300 digital polarimeter was used for measurement
of optical rotations at 25 °C. Mass spectra were recorded on
direct inlet system or LC by MSD trap SL (Agilent Techno-
logies), the HRMS data were obtained using Q-TOF mass
spectrometry.
Table 1 Spiroketal equilibration with different acid catalysts
Entry
Conditions
Ratio (25 : 26)a
1
2
3
4
5
6
7
PPTS, MeOH, 24 h
Sr
CSA, CH2Cl2–MeOH (3 : 1), 24 h
PTSA·H2O, MeOH–CH2Cl2(3 : 1), 24 h
ZnCl2, CH2Cl2, 24 h
ZnBr2, CH2Cl2, 3 h
InCl3, CH3CN, 24 h
90 : 10
82 : 18
70 : 30
52 : 48
90 : 10
Sr
MgBr2, CH2Cl2, 24 h
Sr = Starting material remains.a Product ratio was determined by 1H
NMR spectral analysis (500 MHz).
arrangement. The energy minimized structures (Fig. 3) of 26 and
1 support the diaxial conformation in both the spiroketals, in
agreement with the details from NMR studies.
Finally, spiroketal 26 on hydrogenolysis with Pd/C in MeOH
gave 1 in 89% yield, [α]2D5 −78.0 (c 0.23, CHCl3); lit.7a [α]2D5
−80.4 (c 0.68, CHCl3). The spectral and analytical data of 1 are
in accordance with the data reported.7a
(5S,6R,10S,13R)-6,10-Bis(benzyloxy)-2,2,3,3,5,13,15,15,16,16-
decamethyl-4,14-dioxa-3,15-disilaheptadec-8-yn-7-ol (24). To a
stirred solution of 4 (0.3 g, 0.90 mmol) in THF (3 mL) at
−78 °C, n-BuLi (2.5 M in hexane 0.45 mL, 1.11 mmol) was
added and stirred for 1 h. A solution of aldehyde 3 (0.42 g,
1.36 mmol) in THF (2 mL) was added and stirred for additional
1 h at −78 °C. It was quenched with aq. NH4Cl solution
(10 mL) and extracted with EtOAc (50 mL). Organic layer was
washed with water (25 mL), brine (25 mL) and dried (Na2SO4).
Solvent was evaporated and residue purified by column chrom-
atography (60–120 mesh silica gel, 5% ethyl acetate in pet.
ether) to afford a diastereomeric mixture of 24 (0.48 g, 83%) as
a yellow syrup; [α]2D5 −5.0 (c 0.5 CHCl3); IR (neat): 3448, 2931,
Conclusion
In summary, the first total synthesis of dinemasone A 1 was
achieved from di-O-isopropylidene-D-mannitol and crotyl
alcohol. The key features of this total synthesis are: (i) a double
intramolecular hetero-Michael addition to construct the spiro-
ketal and (ii) Lewis acid promoted spiroepimerization of the
resulting mono anomeric spiroketal to a stable double anomeric
spiroketal.
2858, 1633, 1461, 1375, 1252, 1100, 833, 774, 736, 696 cm−1
;
1H NMR (500 MHz, CDCl3, 298 K): δ 7.35–7.27 (m, 10H,
ArH), 4.87–4.74 (m, 4H, ArCH), 4.60 (bs, 1H, OH), 4.49 (d,
1H, J = 11.9 Hz, OCH), 4.15–4.00 (m, 2H, OCH), 3.79 (m, 1H,
OCH), 3.42 (m, 1H, OCH), 1.87 (m, 1H, CH2), 1.73 (m, 1H,
CH2), 1.57 (m, 2H, CH2), 1.26 (m, 3H, CH3), 1.10 (m, 3H,
Experimental
CH3), 0.90 (m, 18H, C(CH3)3), 0.11–0.02 (m, 12H, SiCH3); 13
C
General
NMR (CDCl3, 125 MHz, 298 K): δ 138.1, 138.0, 137.9, 128.4,
128.3, 128.2, 127.9, 127.8, 127.6, 127.5, 86.0, 85.6, 84.5, 84.4,
74.8, 74.6, 70.4, 70.3, 70.2, 68.9, 68.7, 68.2, 68.1, 61.6, 35.1,
Freshly distilled solvents dried over standard drying agents were
used. Chemicals were purchased and used without further
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Scheme 6 Epimerisation of spiroketal 25 and synthesis of 1.
(18 mg, 0.08 mmol) was added and stirred at room temperature
for 2 h. MeOH was evaporated, and the residue dissolved in
toluene (5 mL) and treated with PTSA (25.0 mg, 0.15 mmol).
After 24 h, Et3N (1 mL) was added to the reaction mixture and
stirred for 10 min. Solvent was evaporated and residue purified
by column chromatography (60–120 mesh silica gel, 5% ethyl
acetate in pet. ether) to furnish 25 (0.15 g, 79%) as a yellow
syrup; [α]2D5 −3.2 (c 0.34, CHCl3); IR (neat): 3433, 3031, 2926,
1729, 1630, 1453, 1381, 1315, 1204, 1075, 1016, 850, 744,
697, 661, 593, 530 cm−1; H NMR (600 MHz, CDCl3, 298 K):
1
Fig. 3 Energy minimized structures of 26 and 1.
7.35–7.27 (m, 10 H, ArH), 4.91 (d, 1H, J = 11.3 Hz, C2-
OCHAr), 4.59 (d, 1H, J = 11.7 Hz, C11-OCHAr), 4.51 (d, 1H, J
= 11.3 Hz, C2-OCHAr), 4.43(d, 1H, J = 11.7 Hz, C11-OCHAr),
4.09 (doublet of sext, 1H, J = 2.0, 6.4 Hz, H-8), 3.90 (m, 2H,
2-H, H-3), 3.35 (t, 1H, J = 2.6 Hz, H-11), 2.88 (d, 1H, J =
15.5 Hz, H-5), 2.77 (d, 1H, J = 15.9 Hz, H-5), 1.86 (m, 2H,
H-10), 1.61 (m, 1H, H-9), 1.36 (m, 1H, H-9), 1.34 (d, 3H, J =
5.6 Hz, C2-CH3), 1.12 (d, 3H, J = 6.4 Hz, C8-CH3); 13C NMR
(CDCl3, 75 MHz, 298 K): δ 206.1, 138.0, 137.3, 128.4, 128.38,
128.34, 128.0, 127.9, 127.7, 100.3, 82.4, 73.3, 72.6, 72.2, 71.2,
67.0, 47.0, 26.2, 21.7, 21.4, 19.7; HRMS (ESI) m/z calculated
for C25H30O5 (M + Na)+ 433.1990, found 433.1990.
35.0, 31.9, 31.8, 29.7, 25.9, 25.8, 23.8, 23.7, 22.7, 20.1, 18.1,
17.9, 17.8, −4.1, −4.3, −4.4, −4.7, −4.8; HRMS (ESI) m/z cal-
culated for C37H60O5Si2 (M + Na)+ 663.3870, found 663.3877.
(5S,6S,10S,13R)-6,10-Bis(benzyloxy)-2,2,3,3,5,13,15,15,16,16-
decamethyl-4,14-dioxa-3,15-disilaheptadec-8-yn-7-one (2). To a
stirred and cooled (0 °C) solution of 24 (0.35 g, 0.55 mmol) in
CH2Cl2 (3 mL), Dess–Martin periodinane (0.28 g, 0.83 mmol)
was added and stirred for 1 h. The reaction was worked up as
described for 16 and the residue was purified by column chrom-
atography (60–120 mesh silica gel, 4% ethyl acetate in pet.
ether) to give 2 (0.31 g, 90%) as a yellow liquid; [α]2D5 −181.8
(c 0.1, CHCl3); IR (neat): 3453, 2927, 2856, 2208, 1679, 1460,
(2S,3S,6S,8R,11S)-3,11-Bis(benzyloxy)-2,8-dimethyl-1,7-dioxa
spiro[5.5] undecan-4-one (26). A solution of 25 (30 mg,
0.07 mmol) in CH2Cl2 (1 mL) was treated with ZnBr2 (1.6 mg,
0.007 mmol) and the suspension was stirred at room temperature
for 3 h. The reaction mixture was treated with aq. NaHCO3 solu-
tion (1 mL) and extracted with CH2Cl2 (2 × 20 mL). Combined
organic layers were washed with water (20 mL), brine (20 mL)
and dried (Na2SO4). Solvent was evaporated and the residue
purified by column chromatography. The first eluted product
(60–120 mesh silica gel, 5% ethyl acetate in pet. ether) was
found to be the recovered 25 (12 mg, 38%), whose spectral data
was identical to 25 prepared from 2.
1
1373, 1252, 1109, 834, 773 cm−1; H NMR (300 MHz, CDCl3,
298 K): δ 7.33–7.22 (m, 10H, ArH), 4.72 (t, 2H, J = 12.1 Hz,
ArCH), 4.49 (d, 1H, J = 11.5 Hz, ArCH), 4.44 (d, 1H, J =
12.0 Hz, ArCH), 4.17 (m, 2H, OCH), 3.75 (sext, 1H, J =
6.1 Hz, OCH), 3.68 (d, 1H, J = 5.5 Hz, OCH), 1.89 (m, 1H,
CH2), 1.75 (m, 1H, CH2), 1.55 (m, 2H, CH2), 1.25 (d, 3H, J =
5.5 Hz, CH3), 1.09 (d, 3H, J = 6.1 Hz, CH3), 0.86 (s, 18H,
C(CH3)3), 0.05 (s, 3H, SiCH3), 0.04 (s, 3H, SiCH3), 0.01 (s, 3H,
SiCH3), 0.00 (s, 3H, SiCH3); 13C NMR (CDCl3, 75 MHz,
298 K): δ 137.3, 128.4, 128.0, 127.9, 127.8, 127.8, 93.7, 89.2,
72.8, 70.9, 69.4, 68.4, 67.9, 34.8, 31.2, 29.7, 25.9, 25.7, 23.8,
22.7, 20.18, −4.3, −4.4, −4.8, −4.9; HRMS (ESI) m/z calculated
for C37H58O5Si2 (M + Na)+ 661.3736, found 661.3715.
Second eluted (60–120 mesh silica gel, 7% ethyl acetate in
pet. ether) was 26 (11 mg, 35%) as a syrup; [α]2D5 −104.9
(c 0.38, CHCl3); IR (neat): 3030, 2920, 2851, 1732, 1496, 1455,
1378, 1358, 1296, 1237, 1209, 1167, 1096, 1009, 979, 930, 885,
(2S,3S,6R,8R,11S)-3,11-Bis(benzyloxy)-2,8-dimethyl-1,7-diox-
aspiro-[5.5] undecan-4-one (25). To a stirred and cooled (0 °C)
solution of 2 (0.30 g, 0.47 mmol) in MeOH (5 mL), CSA
737, 699 cm−1 1H NMR (500 MHz, CDCl3, 298 K): δ
;
7.39–7.28 (m, 10 H, ArH), 4.95 (d, 1H, J = 11.5 Hz, C2-
OCHAr), 4.73 (d, 1H, J = 12.4 Hz, C11-OCHAr), 4.61 (d, 1H,
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J = 12.4 Hz, C11-OCHAr), 4.51 (d, 1H, J = 11.5 Hz, C2-
OCHAr), 4.28 (qd, 1H, J = 6.0, 9.4 Hz, H-2), 3.85 (sext, 1H,
J = 6.0 Hz, H-8), 3.66 (dd, 1H, J = 0.9, 9.4 Hz, H-3), 3.27 (dd,
1H, J = 3.8, 8.5 Hz, H-11), 2.82 (dd, 1H, J = 0.9, 13.7 Hz, H-5),
2.52 (d, 1H, J = 13.7 Hz, H-5), 1.97 (m, 1H, H-10), 1.77 (m,
1H, H-10), 1.68 (m, 2H, H-9), 1.41 (d, 3H, J = 6.4 Hz, C2-
CH3), 1.25 (d, 3H, J = 6.8 Hz, C8-CH3); 13C NMR (CDCl3,
125 MHz, 298 K): δ 204.7, 138.1, 137.5, 128.4, 128.2, 128.1,
127.9, 127.8, 101.5, 84.1, 76.2, 73.1, 71.7, 70.4, 69.5, 47.9,
28.4, 21.5, 20.8, 18.7; HRMS (ESI) m/z calculated for C25H30O5
(M + Na)+ 433.1985, found 433.1980.
(2S,3S,6S,8R,11S)-3,11-Dihydroxy-2,8-dimethyl-1,7-dioxaspiro-
[5.5] undecan-4-one (1) (dinemasone A). A mixture of 26 (8 mg,
0.02 mmol) and 10% Pd/C (cat.) in MeOH (1 mL) was stirred
under a hydrogen atmosphere at room temperature for 8 h. The
reaction mixture was filtered through a pad of celite and washed
with EtOAc (10 mL). Solvent was evaporated and residue
purified by column chromatography (60–120 mesh silica gel,
23% ethyl acetate in pet. ether) to afford 1 (4.0 mg, 89%) as a
solid; m.p. 147–149 °C (lit.7a m.p. 149 °C); [α]2D6 −78.0 (c 0.23,
CHCl3); IR (neat): 3485, 3424, 3383, 2976, 2923, 2854, 1722,
1454, 1378, 1332, 1277, 1165, 1132, 1079, 993, 929, 884,
770 cm−1; 1H NMR (500 MHz, CDCl3): δ 4.07 (dq, 1H, J = 6.0,
9.3 Hz, H2), 3.90 (sext, 1H, J = 6.1 Hz, H-8), 3.83 (ddd, 1H, J =
9.5, 3.5, 1.0 Hz, H-3), 3.55 (m, 1H, J = 7.1, 3.5 Hz, H-11), 3.52
(bs, 1H, OH), 2.90 (d, 1H, J = 13.7 Hz, H-5), 2.83 (dd, 1H, J =
1.0, 13.7 Hz, H-5), 2.49 (d, 1H, J = 5.6 Hz, OH), 1.99 (m, 1H,
H-10), 1.76 (m, 1H, H-10), 1.67 (m, 2H, H-9), 1.47 (d, 3H, J =
6.0 Hz, C2-CH3), 1.26 (d, 3H, J = 6.5 Hz, C8-CH3); 13C NMR
(CDCl3, 125 MHz, 298 K): δ 205.8, 101.3, 78.0, 72.6, 69.9,
69.6, 44.9, 27.5, 24.8, 20.7, 18.7; HRMS (ESI) m/z calculated
for C11H18O5 (M + Na)+ 253.1056, found 253.1051.
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