The stereoselective total synthesis of xestodecalactone C and epi-sporostatin via the Prins cyclisation

Article abstract of DOI:10.1016/j.tetlet.2008.08.096

Syntheses of xestodecalactone C and epi-sporostatin are described utilising Prins cyclisations, Mitsunobu reaction and intramolecular Friedel-Crafts acylation. The approach is convergent and highly stereoselective.

Full text of DOI:10.1016/j.tetlet.2008.08.096

Tetrahedron Letters 49 (2008) 6617–6620
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The stereoselective total synthesis of xestodecalactone C and epi-sporostatin
via the Prins cyclisation
*
J. S. Yadav , N. Thrimurtulu, K. Uma Gayathri, B. V. Subba Reddy, A. R. Prasad
Pheromone Group, Organic Division I, Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 July 2008
Revised 24 August 2008
Accepted 27 August 2008
Available online 30 August 2008
Syntheses of xestodecalactone C and epi-sporostatin are described utilising Prins cyclisations, Mitsunobu
reaction and intramolecular Friedel–Crafts acylation. The approach is convergent and highly
stereoselective.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Xestodecalactones
Prins cyclisation
Mitsunobu reaction
Intramolecular Friedel–Crafts reaction
Marine microorganisms are a source for novel bioactive mole-
cules. More than 800 microorganisms have so far been isolated
from marine sediments and organisms.1,2 Xestodecalactones A, B
and C (II, IIIa and IIIb) were isolated from the fungus Penicillium
cf. montanense, which in turn was isolated from Xestospongia exi-
gua. These molecules are structurally related to a number of com-
pounds isolated from terrestrial fungi, including sporostatin (I) and
curvularins (IV, Va and Vb) (Fig. 1).
Sporostatin (M5032, I) isolated from the fungus Sporormiella sp.,
is an inhibitor of cyclic adenosine 30,50-monophosphate phosphodi-
esterase.1 All these compounds contain a 10-membered macrolide
with 1,3-dihydroxybenzene ring. Xestodecalactones A–C have been
found to exhibit antibacterial and antifungal activities.2 They are
also found to be a specific inhibitor of epidermal growth factor
(EGF) receptor, tyrosine kinase in vitro. In view of their biological
activity, we were interested in the total synthesis of xestodecalac-
tone C and sporostatin by means of Prins cyclisation.
OH
O
OH
1
O
9
1
7
7
The Prins cyclisation is a powerful synthetic tool for the con-
struction of multi-substituted tetrahydropyran systems and has
been utilised in the synthesis of several natural products.3 Our
group has made a significant effort to explore the utility of Prins
cyclisation in the synthesis of various polyketide intermediates
and applied it to the total synthesis of some natural products.4
As a part of our ongoing programme on the total synthesis of nat-
ural products, we herein report the synthesis of xestodecalactone C
and epi-sporostatin.
In our retrosynthetic analysis (Scheme 1), we envisaged that the
target molecules (IIIb and I) could be achieved from a common
intermediate 12, which was viewed as being obtained from a Mits-
unobu reaction and intramolecular Friedel–Crafts acylation. It was
proposed to obtain the 1,3-diol 8 from 2,4,6-trisubstituted tetrahy-
dropyran 4, which in turn would be obtained via the Prins cyclisa-
tion of homoallylic alcohol 3 and acetaldehyde.
11
R
R
11
13
13
5
HO
HO
O
X
HO
HO
O
5
O
O
O
O
I
II
OH
O
OH
O
OH
9
1
1
9
7
7
11
13
O
5
5
S
O
IIIa: 9S,11R
IIIb: 9R,11R
IV: X=H
Va: X=OH;9-R
Vb:X=OH;9-S
Figure 1. Sporostatin (I), xestodecalactone A (II), xestodecalactone B, C (IIIa, IIIb)
and curvularins (IV, Va and Vb).
Accordingly, the synthesis of xestodecalactone (IIIb) and epi-
sporostatin (I) began with chiral homoallyl alcohol (3). The precur-
sor 3 was prepared in two steps by Cu(I)-mediated regioselective
* Corresponding author. Tel.: +91 40 27193030; fax: +91 40 27160512.
E-mail address: yadavpub@iict.res.in (J. S. Yadav).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.096

6618
J. S. Yadav et al. / Tetrahedron Letters 49 (2008) 6617–6620
OMe O
OH
O
OMe
OTBS
I, III b
MeO
MeO
OH
O
O
O
9
12
OH OTBS
OH
H3C
OH
OH
H3C
O
4
3
8
Scheme 1. Retrosynthetic analysis of xestodecalactone C and epi-sporostatin.
opening5 of S-(ꢀ)-benzyl glycidyl ether with vinylmagnesium bro-
mide and by subsequent reductive cleavage of the benzyl ether
with Li or Na in liquid ammonia. Prins cyclisation of 3 with acetal-
dehyde in the presence of TFA (10 equiv), followed by hydrolysis of
the resulting trifluoroacetate, gave trisubstituted pyran 4 in 52%
yield.6 The stereochemistry of 4 was assumed to be in anticipated
CH2=CHMgBr, CuCN
-78 oC to -40 oC, 4 h
Li, Liq. NH3
OH
OBn
OBn
O
20 min, 75%
OH
92%
1
3
OH
2
OH
OH
CH3CHO, TFA
CH2Cl2 then
TEA, TsCl, CH2Cl2
0 oC-r.t., 3 h, 96%
OTs
K2CO3, MeOH
r.t., 3 h, 52%
OH
H3C
O
H3C
O
5
4
OTBS
OTBS
NaI, acetone
reflux, 24 h.
TBSCl, DMAP
imidazole, CH2Cl2
94%
OTs
I
0 oC-r.t., 3 h, 99%
H3C
O
H3C
O
6
7
OMe
OMe
OTBS
O
Zn, EtOH
reflux, 1 h
OTBS
OH
MeO
OH
TPP, DEAD, 86%
H3C
96%
MeO
O
8
O
9
OMe
OTBS
CHO
O3, TPP, CH2Cl2
-78 oC
NaClO2, NaH2PO4
90%
MeO
O
O
10
OMe
OTBS
OMe
OH
O
CO2H
TFA, TFAA
r.t., 41%
MeO
MeO
O
O
O
O
AlI3, Bu4N+I-
, Bu4N+I-
AlI3
benzene,10 oC
45 min, 96%
12
11
benzene, rt
12h, 94%
OH
1
O
OH
O
OH
9
7
R
11
R
O
13
5
HO
O
HO
O
O
I
IIIb
Scheme 2. Synthetic sequence of IIIb and I.

J. S. Yadav et al. / Tetrahedron Letters 49 (2008) 6617–6620
6619
line with previous results.4–6 However, it was later proved after
elaborating compound 4 to the target molecule which in all re-
spects was identical with the reported one. The chemoselective
tosylation of primary alcohol in compound 4 with 1.1 equiv of tosyl
chloride in the presence of TEA in DCM gave the corresponding tos-
ylate 5 in 96% yield.7,12 TBS protection of the secondary alcohol 5
with TBSCl, DMAP and imidazole provided the corresponding TBS
ether 6 in 91% yield. Treatment of tosylate 6 with NaI in refluxing
acetone gave the respective iodo compound 7 in 94% yield, which
on exposure to activated Zn in refluxing ethanol furnished key
intermediate 8 with the required anti-1,3-diol system in 96% yield.
Alcohol 8 when subjected to standard Mitsunobu reaction condi-
tions using DEAD, PPh3 and 3,5-dimethoxyphenylacetic acid in
THF gave compound 9 in 86% yield.8 Ozonolysis of the olefin 9 fol-
lowed by further oxidation with NaClO2 and NaH2PO4 gave the cor-
responding acid 11 in 90% yield. The desired macrolide 12 was
obtained in 41% yield (at 25 °C, 8 h) by intramolecular Friedel–
Crafts reaction of the carboxylic acid 11 with a mixture of trifluo-
roacetic acid and trifluoroacetic acid anhydride.9 Demethylation of
12 using freshly prepared AlI3 at 10 °C for 45 min gave the target
molecule IIIb9e–g in 96% yield, whereas the same reaction at room
temperature over 12 h furnished I in 94% yield.9a,9d
The formation of IIIb and I in a single step from 12 under differ-
ent reaction conditions maybe attributed to the versatility of alu-
minium iodide. Deprotection of the methoxy groups of 12
occurred using the freshly prepared AlI3. Upon prolonged reaction
conditions, aluminium iodide, due to its acidic property, has been
observed to catalyse the dehydration of the free OH present in
12, along with the expected demethylation thereby resulting in
the formation of I. The target molecule IIIb was identical in all re-
spects to the natural product (Scheme 2).10
The spectral data and melting point of I were identical with
those of the natural product.11 The specific rotation of our syn-
thetic epi-sporostatin I was +18.8°, which is exactly the opposite
optical rotation to that reported by Yaginuma and co-workers,11
thereby confirming stereochemistry of the chiral centre at C11 car-
bon as ‘R’. The specific rotation of naturally occurring sporostatin
was ꢀ18.8° for which the configuration at C11 carbon centre was
reported as (S). Therefore, the product I formed from 12 is the
unnatural epi-sporostatin with ‘R’ configuration.
In conclusion, we have proved the versatility of the Prins cycli-
sation in natural product synthesis by achieving the stereoselective
synthesis of xestodecalactone (IIIb) and sporostatin (I), by employ-
ing a 10-step sequence. Further applications of the Prins cyclisation
in the synthesis of natural products are in progress, and will be dis-
closed in due course.
2683–2686; (c) Cossey, K. N.; Funk, R. L. J. Am. Chem. Soc. 2004, 126, 12216–
12217; (d) Crosby, S. R.; Harding, J. R.; King, C. D.; Parker, G. D.; Willis, C. L. Org.
Lett. 2002, 4, 3407–3410; (e) Marumoto, S.; Jaber, J. J.; Vitale, J. P.; Rychnovsky,
S. D. Org. Lett. 2002, 4, 3919–3922; (f) Kozmin, S. A. Org. Lett. 2001, 3, 755–758;
(g) Jaber, J. J.; Mitsui, K.; Rychnovsky, S. D. J. Org. Chem. 2001, 66, 4679–4686;
(h) Kopecky, D. J.; Rychnovsky, S. D. J. Am. Chem. Soc. 2001, 123, 8420–8422; (i)
Rychnovsky, S. D.; Thomas, C. R. Org. Lett. 2000, 2, 1217–1219; (j) Rychnovsky,
S. D.; Yang, G.; Hu, Y.; Khire, U. R. J. Org. Chem. 1997, 62, 3022–3023; (k) Su, Q.;
Panek, J. S. J. Am. Chem. Soc. 2004, 126, 2425–2430.
5. Bonini, C.; Chiummiento, L.; Lopardo, M. T.; Pullex, M.; Colobert, F.; Solladie, G.
Tetrahedron Lett. 2003, 44, 2695–2697.
6. Yadav, J. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron Lett. 2005, 46, 2133–2136.
7. Yadav, J. S.; Sridhar Reddy, M.; Purushothama Rao, P.; Prasad, A. R. Tetrahedron
Lett. 2006, 47, 4397–4401.
8. Mitsunobu, O. Synthesis 1981, 1.
9. (a) Liang, Q.; Zhang, J.; Quan, W.; Sun, Y.; She, X.; Pan, X. J. Org. Chem. 2007, 72,
2694–2697; (b) Liang, Q.; Sun, Y.; Xunyu, B.; She, X.; Pan, X. J. Org. Chem. 2007,
72, 9846–9849; (c) Kreipl, A. T.; Reid, C.; Steglich, W. Org. Lett. 2002, 4, 3287;
(d) Konwar, D.; Boruah, R. C.; Sandhu, J. S. Tetrahedron Lett. 1990, 30, 1063–
1064; (e) Bracher, F.; Schulte, B. Liebigs. Ann. Recl. 1997, 1979–1980; (f)
Bringmann, G.; Lang, G.; Michel, M.; Heubes, M. Tetrahedron Lett. 2004, 45,
2829–2832; (g) Hasar, R. A.; Khan, R. A.; Deshpande, V. H.; Ayyanga, N. R.
Tetrahedron Lett. 1991, 32, 1599–1600.
10. Edrada, R. A.; Heubes, M.; Brauers, G.; Wray, V.; Berg, A.; Fe, U. G.; Wohlfarth,
M.; Muhlbacher, J.; Schaumann, K.; Bringmann, S. G.; Proksch, P. J. Nat. Prod.,
2002. 1598–1604.
11. Kinoshita, K.; Sasaki, T.; Awata, M.; Takada, M.; Yaginuma, S. J. Antibiot. 1997,
50, 961.
12. Experimental procedure: (2S,4R,6S)-4-hydroxy-6-methyl-6-methyltetrahydro-2H-
2-pyranyl)methyl-4-methyl-1-benzenesulfonate (5): To a solution of diol 4 (2.0 g,
13.68 mmol) in dry CH2Cl2 (15.0 mL), triethylamine (3.81 mL, 27.36 mmol)
was added at 0 °C. Then tosyl chloride (2.86 g, 15.04 mmol) was added over
2 h. The resulting mixture was allowed to warm to room temperature, and
stirred for 3 h. Then the reaction mixture was treated with aqueous 1 N HCl
(10 mL), and extracted with CH2Cl2 (3 ꢁ 30 mL). The organic layer was washed
with saturated NaHCO3 (15 mL) and water (15 mL). The combined organic
phases were dried over Na2SO4 and concentrated under reduced pressure.
Flash chromatography of the crude product afforded tosylate 5 (3.94 g, 96%) as
a gummy liquid. Rf = 0.5 (SiO2, 80% EtOAc in hexane). ½a D25
ꢂ
+34.8 (c 1.0, CHCl3);
1H NMR (CDCl3, 200 MHz): d 7.75 (d, 2H, J = 8.0 Hz), 7.25 (d, 2H, J = 8.0 Hz),
4.04–3.87 (m, 2H), 3.82–3.64 (m, 1H), 3.58–3.42 (m, 1H), 3.42–3.28 (m, 1H),
2.45 (s, 3H), 2.13 (m, 1H), 1.90–1.80 (m, 3H), 1.15 (d, 3H, J = 6.6 Hz); 13C NMR
(CDCl3, 75 MHz): d 145.1, 132, 129, 127, 72.8, 72.12, 67.35, 42.36, 36.54, 21.73;
IR (Neat):
m
3410, 2926, 2855, 1741, 1597, 1451, 1358, 1176, 974 cmꢀ1; HRMS
calcd for C14H20O5NaS (M+Na)+ 323.0929. Found: 323.0932. (2S,4S)-4-(tert-
Butyl-dimethyl-silanyloxy)-hept-6-en-2-ol (8): To the iodide 7 (2.2 g, 5.94 mmol)
in ethanol (80 mL), commercial zinc dust (5.82 g, 89.10 mmol) was added. The
resulting mixture was refluxed for 1 h, and then cooled to 25 °C. Addition of
solid ammonium chloride (8.17 g) and ether (120 mL) followed by stirring for
5 min gave a gray suspension. The suspension was filtered through Celite, and
filtrate was concentrated in vacuo. Purification by flash chromatography gave 8
(1.39 g, 96%) as a colourless liquid. Rf = 0.4 (SiO2, 10% EtOAc in hexane). ½a D25
ꢂ
+39.5 (c 1.0, CHCl3). 1H NMR (CDCl3, 300 MHz): d 5.82–5.60 (m, 1H), 5.12–5.00
(m, 2H), 4.19–3.82 (m, 2H), 2.35–2.21 (m, 2H), 1.59–1.50 (m, 2H), 1.14 (d, 3H,
J = 6.2 Hz), 0.89 (s, 9H), 0.08 (s, 6H); 13C NMR (CDCl3, 75 MHz): d 135.0, 117.3,
71.1, 64.3, 43.0, 32.4, 25.7, 18.6, ꢀ4.2; IR (Neat):
1034, 916, 702 cmꢀ1; HRMS calcd for C13H28O2NaSi (M+Na)+, 267.1756. Found:
267.1766. (1R,3S)-(3,5-Dimethoxy-phenyl)-aceticacid-3-(tert-butyl-dimethyl-
silanyloxy)-1-methyl-hex-5-enyl ester (9): To a well-stirred solution of alcohol
(0.20 g, 0.81 mmol) and triphenylphosphine (0.32 g, 1.23 mmol) in dry
benzene (5 mL) at room temperature was added solution of 3,5-
m 3452, 2942, 1640, 1098,
8
a
dimethoxyphenylacetic acid (0.16 g, 0.81 mmol) and DEAD (0.21 g,
1.23 mmol) in benzene (5 mL). The mixture was stirred for 14 h. Solvent was
evaporated, and the residue was washed with dry ether and filtered through a
sintered funnel. The filtrates were dried over anhydrous Na2SO4, and
evaporation of the solvent followed by chromatography of the crude residue
afforded pure ester 9 (0.29 g, 86% yield) as a pale pink coloured viscous liquid.
Acknowlegements
N.T. and K.U.G. thank CSIR, New Delhi for the award of fellow-
ships and also thank DST for the financial assistance under J. C.
Bose fellowship scheme.
½ ꢂ
a 2D5 +4.1 (c 1.0, CHCl3); 1H NMR (CDCl3, 300 MHz): d 6.4–6.32 (m, 2H), 6.29 (s
1H), 5.80–5.60 (m, 1H), 5.05–4.09 (m, 2H), 3.79 (s, 6H), 3.68–3.52 (m, 1H), 3.48
(s, 2H), 2.30–2.05 (m, 2H), 1.80–1.50 (m, 2H), 1.20 (d, 3H, J = 5.8 Hz), 0.90 (s,
9H), 0.08 (s, 6H); 13C NMR (CDCl3, 75 MHz): d 172.2, 160.7, 134.7, 117.0, 107.0,
References and notes
99.1, 68.7, 55.2, 42.9, 42.0, 41.2, 25.7, 20.3. IR (Neat):
m
3075, 2930, 2856, 1733,
HRMS calcd for
1600, 1465, 1431, 1352, 1293, 1252, 1155, 915 cmꢀ1
;
1. Sponga, F.; Cavaletti, L.; Lazzarini, A.; Borghi, A.; Ciciliato, I.; Losi, D.; Marinelli,
F. J. Biotechnol. 1999, 70, 65–69.
C23H38O5NaSi (M+Na)+ 445.2386. Found: 445.2400. (1R,3S)-3-(tert-Butyl-
dimethyl-silanyloxy)-5-[2-(3,5-dimethoxy-phenyl)-acetoxy]-hexenoic acid (11):
Ozone was bubbled through a solution of 9 (0.15 g, 0.35 mmol) in CH2Cl2
(2 mL) at –78 °C until no unreacted starting material was observed on TLC. The
reaction mixture was purged with N2 to remove the excess of ozone and cooled
to 0 °C, Ph3P (0.18 g, 0.70 mmol) was added, and the mixture was stirred for
2 h. The mixture was concentrated in vacuo. After adding hexane, the mixture
was filtered through Celite pad. Then the residue was washed with hexane, and
the filtrate was dried over Na2SO4, concentrated under reduced pressure and
the crude aldehyde 10 was subjected to the next reaction without further
purification. To a stirred solution of the crude aldehyde 10 in t-BuOH (1 mL)
was added methyl-2-butene (0.5 mL) in t-BuOH (0.5 mL). The reaction mixture
was cooled (0 °C) and treated with a solution of NaClO2 (0.086 g, 0.95 mmol)
2. (a) Bernan, V. S.; Greenstein, M.; Maiese, W. M. Adv. Appl. Microbiol. 1997, 43,
57–90; (b) Fenical, W.; Jensen, P. R. Annu. Rev. Microbiol. 1994, 48, 559–584.
3. (a) Barry, C. St. J.; Crosby, S. R.; Harding, J. R.; Hughes, R. A.; King, C. D.; Parker,
G. D.; Willis, C. L. Org. Lett. 2003, 5, 2429–2432; (b) Yang, X.-F.; Mague, J. T.; Li,
C.-J. J. Org. Chem. 2001, 66, 739–747; (c) Yadav, J. S.; Reddy, B. V. S.; Sekhar, K.
C.; Gunasekar, D. Synthesis 2001, 6, 885–888; (d) Yadav, J. S.; Reddy, B. V. S.;
Reddy, M. S.; Niranjan, N. J. Mol. Catal. A: Chem. 2004, 210, 99–103; (e) Yadav, J.
S.; Reddy, B. V. S.; Reddy, M. S.; Niranjan, N.; Prasad, A. R. Eur. J. Org. Chem. 2003,
1779–1783; (f) Kwon, M. S.; Woo, S. K.; Na, S. W.; Lee, E. Angew. Chem., Int. Ed.
2008, 47, 1733–1735.
4. (a) Aubele, D. L.; Wan, S.; Floreancig, P. E. Angew. Chem., Int. Ed. 2005, 44, 3485–
3488; (b) Barry, C. S.; Bushby, N.; Harding, J. R.; Willis, C. S. Org. Lett. 2005, 7,

6620
J. S. Yadav et al. / Tetrahedron Letters 49 (2008) 6617–6620
and NaH2PO4 (0.344 g, 2.87 mmol) in H2O (1 mL). After 1.5 h, the reaction
J = 11.2, 5.6 Hz), 3.95 (br s, 1H), 3.82 (d, 1H, J = 18.8 Hz), 3.48 (d, 1H,
J = 18.8 Hz), 3.08 (dd, 1H J = 14.8, 10.4 Hz), 2.81 (d, 1H, J = 14.6 Hz), 1.83 (d,
1H, J = 13.0 Hz), 1.64 (dd, 1H, J = 14.8, 11.2 Hz), 1.08 (d, 3H, J = 6.5 Hz). 13C NMR
(DMSO, 75 MHz): d 204.0, 167.4, 159.1, 157.0, 134.1, 121.8, 110.0, 101.1, 70.6,
mixture was diluted with brine (3 mL) and Et2O (3 mL). The organic phase was
separated, and the aqueous phase was extracted with Et2O. The combined
organic phases were washed with brine, dried over anhydrous Na2SO4,
concentrated in vacuo and purified by flash chromatography (Et2O) to afford
67.8, 55.3, 45.9, 20.6. IR (Neat):
MS(LCMS): m/z 303 (M+Na)+. HRMS calcd for C14H16O6: 303.0839. Found:
303.0843. epi-sporostatin (I): To suspension of aluminium (0.042 g,
1.56 mmol) in dry benzene was added solution of iodine (0.29 g,
m .
3343, 2923, 1739, 1650, 1376 cmꢀ1
the acid 11 (0.12 g, 90%). Rf = 0.25 (SiO2, 30% EtOAc in hexane). ½a D25
ꢂ
+3.0 (c 1.0,
CHCl3). 1H NMR (CDCl3, 300 MHz): d 6.47–6.30 (m, 2H), 5.17–4.90 (m, 1H),
4.18–4.01 (m, 1H), 3.76 (s, 6H), 3.50 (s, 2H), 2.46-2.42 (m, 2H), 2.00–1.51 (m,
2H), 1.23 (d, 3H, J = 5.8 Hz), 0.85 (s, 9H), 0.03 (s, 6H); 13C NMR (CDCl3,75 MHz):
d 179.0, 172.9, 161.0, 150.5, 146.1, 128.7, 123.3, 107.4, 99.0, 69.3, 55.2, 41.7,
a
a
1.16 mmol) in dichloromethane. The mixture was refluxed for 1 h, cooled to
room temperature, and then n-Bu4N+Iꢀ (0.0018 g, 0.0050 mmol) and 12
(0.012 g, 0.038 mmol) in dry benzene (8 mL) were added. The mixture was
stirred for 12 h at room temperature and quenched with water. After
acidification with 2 N HCl, the mixture was extracted with EtOAc
(3 ꢁ 10 mL). The organic phase was washed with brine, dried over Na2SO4,
filtered and concentrated in vacuo. The residue was purified by flash
chromatography on silica gel (hexanes/EtOAc, 2:1) to afford epi-sporostatin I
38.3, 19.5, 18.3; IR (Neat):
m 3759, 3678, 3449, 2926, 2855, 1740, 1602, 1463,
1376, 1050, 835 cmꢀ1 HRMS calcd for C22H36O7NaSi (M++Na): 463.2128.
.
Found: 463.2116. Xestodecalactone C (5a): Iodine (0.29 g, 1.16 mmol) was
added to a mixture of aluminium (0.042 g, 1.56 mmol) in dry benzene. The
mixture was refluxed for 1 h, and then cooled to room temperature. A mixture
of n-Bu4N+Iꢀ (0.0018 g, 0.0050 mmol) and compound 12 (0.012 g, 0.038 mmol)
in dry benzene (8 mL) was added. The resulting mixture was stirred for 45 min
at 10 °C and quenched with water. After acidification with 2 N HCl, the mixture
was extracted with EtOAc (3 ꢁ 10 mL). The organic phase was washed with
brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was
purified by flash chromatography on silica gel (hexanes/EtOAc, 1:1) to afford
the xestodecalactone IIIb (0.010 mg, 96%) as a white solid, mp 167–168 °C;
(0.009 g, 94%) as a white solid, mp 198–200 °C; ½a D25
ꢂ
+18.8 (c 0.5, CH3OH);
d 13.59 (s, 1H), 10.75 (s, 1H), 6.80 (d, 1H,
1HNMR (DMSO, 300 MHz):
J = 15.8 Hz), 6.32 (s, 1H), 6.22 (s, 1H), 6.01–5.92 (m, 1H), 5.11–5.01 (m, 1H),
4.07 (d, 1H, J = 16.8 Hz), 3.92–3.82 (m, 1H), 2.64–2.54 (m, 1H), 1.36 (d, 3H,
J = 6.5 Hz). 13C NMR (DMSO, 75 MHz): d 198, 173.1, 167.4, 163.7, 140, 138,
136.3, 114.5, 111.7, 102.1, 74.9, 43.9, 41.6, 19.6. IR (Neat):
m 3424, 2255, 2128,
½
a 2D5
ꢂ
+24 (c 0.5, CH3OH); 1H NMR (DMSO, 300 MHz): d 9.90 (s, 1H), 9.70 (s, 1H),
6.27 (d, 1H, J = 1.6 Hz), 6.09 (s, 1H), 4.76 (d, 1H, J = 4.0 Hz), 4.72 (dd, 1H,
1739, 1650, 1376 cmꢀ1. MS(LCMS): m/z 263 (M+ 1) +. HRMS calcd for C14H15O4:
263.0919. Found: 263.0916.