Enantioselective synthesis of decarestrictine J

Article abstract of DOI:10.1016/j.tetlet.2009.10.035

An efficient total synthesis of decarestrictine J has been achieved using ring-closing metathesis and Yamaguchi esterification as key steps. The stereogenic centres were generated by means of iterative hydrolytic kinetic resolution (HKR) of racemic epoxides.

Full text of DOI:10.1016/j.tetlet.2009.10.035

Tetrahedron Letters 50 (2009) 7188–7190
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Tetrahedron Letters
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Enantioselective synthesis of decarestrictine J
*
Partha Sarathi Chowdhury, Priti Gupta, Pradeep Kumar
Organic Chemistry Division, National Chemical Laboratory, Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient total synthesis of decarestrictine J has been achieved using ring-closing metathesis and
Yamaguchi esterification as key steps. The stereogenic centres were generated by means of iterative
hydrolytic kinetic resolution (HKR) of racemic epoxides.
Received 19 August 2009
Revised 6 October 2009
Accepted 8 October 2009
Available online 13 October 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Decanolides
Hydrolytic kinetic resolution
Yamaguchi esterification
Ring-closing metathesis
Epoxides
1. Introduction
epoxide into an enantiomerically enriched epoxide and diol, which
serve as useful precursor in the synthesis of various compounds of
Decanolides have attracted considerable attention over the last
few years1 of which an important class of compounds is the deca-
restrictine family. The decarestrictines are secondary metabolites
that were isolated from various Penicillium strains and identified
as bioactive compounds by chemical screening2–4 (Fig. 1). Decare-
strictine J,4 a 10-membered lactone, has been isolated as a minor
component of the decarestrictine family2,3 from a culture broth
of Penicillium simplicissimum and was shown to inhibit the biosyn-
thesis of cholesterol. The absolute stereochemistry of decarestric-
tine J itself has not been reported. However, because it coexisted
with decarestrictine B, whose absolute configuration had been
determined by an X-ray analysis, Yamada et al.5 suggested
(7R,9R)-stereochemistry for natural (ꢀ)-decarestrictine J. Only
one total synthesis of the proposed structure of (ꢀ)-decarestrictine
J (1a) has been reported in the literature using a Sharpless asym-
metric epoxidation and samarium(II) iodide-promoted Reformat-
sky reaction as the key steps.5
biological importance.10
Our retrosynthetic analysis for the synthesis of decarestrictine J is
based on convergent approach as outlined in Scheme 1. We envi-
sioned that thering-closingcould be effectedbyring-closingmetath-
esis of diene 17. Diene 17 could be prepared by intermolecular
Yamaguchi esterification of the alcohol 10 and acid 16. Alcohol 10
could be obtained from rac-propylene oxide (2) via iterative HKR,
whileacidfragment16could be preparedfrom 1,3-propane diol (11).
2. Synthesis of alcohol fragment 10
As shown in Scheme 2, synthesis of alcohol fragment 10 started
with a Jacobsen’s hydrolytic kinetic resolution of rac-epoxide 2
O
O
O
O
As a part of our research programme aimed at developing enan-
tioselective synthesis of biologically active natural products based
on hydrolytic kinetic resolution (HKR),6 we became interested in
devising a simple and concise route to decarestrictine J. Herein
we report our successful endeavours towards the total synthesis
of 1a employing HKR,7 Yamaguchi esterification8 and ring-closing
metathesis (RCM)9 as the key steps.
O
HO
O
O
OH
Decarestrictine J 1a
Decarestrictine B 1b
O
O
O
O
OH
OH
The HKR method involves the readily accessible cobalt-based
chiral salen complex as catalyst and water to resolve a racemic
O
OH
OH
Decarestrictine C 1d
Decarestrictine G 1c
* Corresponding author. Tel.: +91 20 25902050; fax: +91 20 25902629.
E-mail address: pk.tripathi@ncl.res.in (P. Kumar).
Figure 1. Examples of 10-membered lactones.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.035

P. S. Chowdhury et al. / Tetrahedron Letters 50 (2009) 7188–7190
7189
O
O
O
OTBS
16
OH OMEM
O
O
1
+
HO
MEMO
OTBS
HO
O
10
17
OTBS
7
O
HO
OH
11
O
2
Scheme 1. Retrosynthetic analysis of decarestrictine J.
ment of the mesylate furnished the epoxide 7 in 61% overall yield.
Epoxide 7 on reaction with dimethylsulfonium methylide12 affor-
ded one-carbon homologated allylic alcohol 9 in 70% yield, which
was protected as its MEM ether followed by TBDMS removal to fur-
nish the alcohol fragment 10 in 80% yield (Scheme 2). It may be
noted that the alcohol fragment 10 could be synthesised in eight
steps employing iterative HKR method, while our previous method
involving Sharpless asymmetric dihydroxylation required three
additional steps to prepare the same alcohol fragment.6h
OH
a
O
O
O
+
OH
(R)-2
2
3
OTBS
OH
d
c
b
5
(R)-2
4
OTBS
OTBS
OTBS
OH
g
e
O
O
+
OH
6
8
7
3. Synthesis of acid fragment
OTBS
OH
OTBS
f
OTBS
OMs
O
OH
h
As shown in Scheme 3, synthesis of acid fragment 16 started
from 1,3-propanediol (11). Selective monoprotection of hydroxy
group with p-methoxybenzyl bromide (PMBBr) in the presence of
NaH afforded compound 12 in 89% yield, which was subjected to
Swern oxidation13 followed by the reaction of the resulting alde-
hyde with allylmagnesium bromide to furnish the homoallyllic
alcohol 13 in 80% yield.
OPiv
8
7
OTBS
OTBS
OH
OH OMEM
i
O
10
7
9
Scheme 2. Reagents and conditions: (a) (R,R)-salen-Co-(OAc)(0.5 mol %), dist. H2O
(0.55 equiv), 0 °C, 14 h, (45% for (R)-2, 43% for 3); (b) vinylmagnesium bromide THF,
CuI, ꢀ20 °C, 90%, 12 h; (c) TBDMSCl, imidazole, CH2Cl2, 4 h, 0 °C to rt, 95%; (d) m-
CPBA, CH2Cl2, 0 °C to rt, 93%, 2 h; (e) (S,S)-salen-Co-(OAc) (0.5 mol %), dist. H2O
(0.55 equiv), 0 °C, 20 h, (70% for 7, 22% for 8); (f) (i) PivCl, Et3N, cat. DMAP, rt, 2 h;
(ii) MsCl, Et3N, DMAP, 0 °C to rt, 1 h; (g) K2CO3, MeOH, rt, overnight (61% for three
steps); (h) (CH3)3SI, 2 h, n-BuLi, THF, 70%; (i) (i) DIPEA, MEMCl, CH2Cl2, 0 °C to rt,
8 h; (ii) TBAF, THF, 0 °C to rt, 5 h, 80% from two steps.
Protection of the hydroxy group of 13 as its TBDMS ether fol-
lowed by removal of the PMB group14 by DDQ resulted in the pri-
mary alcohol 15 with 94% yield. The alcohol 15 was oxidised to the
aldehyde using 2-iodoxybenzoic acid (IBX) followed by subsequent
oxidation using NaClO2 to give the required acid fragment 1615 in
80% yield.
4. Coupling of acid and alcohol fragments
using (R,R)-salen-Co-(OAc) catalyst to give epoxide (R)-2 as a single
isomer which was easily isolated from diol 3 by distillation.7b
Epoxide (R)-2 was treated with vinylmagnesium bromide in the
presence of cuprous iodide to give homoallylic alcohol 4 in 90%
yield.6e Protection of the hydroxy group of 4 as a TBDMS ether fol-
lowed by epoxidation with m-CPBA afforded epoxide 6. The epox-
ide thus obtained was found to be a mixture of two diastereomers
(anti:syn/3:1). In order to improve the diastereoselectivity, we
attempted the hydrolytic kinetic resolution (HKR) method as de-
picted in Scheme 2. Thus, the HKR was performed on epoxide 6
with (S,S)-salen-Co-(OAc) complex (0.5 mol %) and water
(0.55 equiv) in THF (0.55 equiv) to afford the diastereomerically
pure epoxide 7 in 70% yield (>95% ee) and diol 8 in 22% yield. As
the HKR method provided the desired epoxide 7 along with un-
wanted diol 8, we thought that it would be appropriate to convert
diol 8 into the required epoxide 7 via internal nucleophilic substi-
tution of a secondary mesylate.11 Accordingly chemoselective
pivalation of diol 8 with pivaloyl chloride followed by mesylation
of the secondary hydroxyl and treatment of the crude mesylate
with K2CO3 in methanol led to the deprotection of the pivalate
ester. Concomitant ring closure via intramolecular SN2 displace-
With substantial amount of both the fragments in hand the
coupling of alcohol 10 and acid 16 was achieved by using the
a
b
PMBO
OH
HO
OH
OH
12
11
OTBS
c
PMBO
PMBO
13
14
OTBS
OTBS
e
d
HOOC
HO
16
15
Scheme 3. Reagents and conditions: (a) PMBBr, NaH, THF, 0 °C to rt, 5 h, 89%; (b) (i)
(COCl)2, DMSO, ꢀ78 °C to ꢀ60 °C, Et3N, CH2Cl2; (ii) allylmagnesium bromide, THF,
80%; (c) TBDMSCl, imidazole, CH2Cl2, 0 °C to rt, 90%; (d) DDQ, CH2Cl2/H2O (1:1), rt,
1 h, 94%; (e) (i) IBX, EtOAc, reflux; (ii) NaClO2, NaH2PO4, DMSO, overnight, 80% from
two steps.

7190
P. S. Chowdhury et al. / Tetrahedron Letters 50 (2009) 7188–7190
structure–activity relationship. Currently work is in progress in
this direction.
OTBS
16
OH OMEM
a
+
HOOC
10
Acknowledgements
O
O
O
P.S.C. and P.G. thank CSIR, New Delhi, for the award of senior
research fellowship and research associateship, respectively.
Financial support for the project (Grant No. SR/S1/OC-40/2003)
from the Department of Science & Technology, New Delhi, is grate-
fully acknowledged.‘‘
O
MEMO
MEMO
OTBS
MEMO
OTBS
18
17
b
References and notes
O
O
O
1. (a) Dräger, G.; Kirschning, A.; Thiericke, R.; Zerlin, M. Nat. Prod. Rep. 1996, 13,
365–375; (b) Collins, I. J. Chem. Soc., Perkin Trans. 1 1999, 1377–1395; (c) Longo
Júnior, L. S.; Bombonato, F. I.; Ferraz, H. M. C. Quim. Nova 2007, 30, 415–424; (d)
Riatto, V. B.; Pilli, R. A.; Victor, M. M. Tetrahedron 2008, 64, 2279–2300.
2. Grabley, S.; Granzer, E.; Hütter, K.; Ludwig, D.; Mayer, M.; Thiericke, R.; Till, G.;
Wink, J.; Philipps, S.; Zeeck, A. J. Antibiot. 1992, 45, 56–65.
c
O
OH
MEMO
OH
20
3. Göhrt, A.; Zeeck, A.; Hütter, K.; Kirsch, R.; Kluge, H.; Thiericke, R. J. Antibiot.
1992, 45, 66–73.
19
4. Grabley, S.; Hammann, P.; Hütter, K.; Kirsch, R.; Kluge, H.; Thiericke, R.; Mayer,
M.; Zeeck, A. J. Antibiot. 1992, 45, 1176–1181.
5. Yamada, S.; Tanaka, A.; Oritani, T. Biosci., Biotechnol., Biochem. 1995, 59, 1657–
1660.
O
O
e
d
O
O
6. (a) Gupta, P.; Naidu, S. V.; Kumar, P. Tetrahedron Lett. 2004, 45, 849–851; (b)
Gupta, P.; Naidu, S. V.; Kumar, P. Tetrahedron Lett. 2005, 46, 6571–6573; (c)
Pandey, S. K.; Kumar, P. Tetrahedron Lett. 2005, 46, 6625–6627; (d) Kumar, P.;
Naidu, S. V. J. Org. Chem. 2006, 71, 3935–3941; (e) Kumar, P.; Gupta, P.; Naidu,
S. V. Chem. Eur. J. 2006, 12, 1397–1402; (f) Pandey, S. K.; Kumar, P. Synlett 2007,
2894–2896; (g) Naidu, S. V.; Kumar, P. Tetrahedron Lett. 2007, 48, 3793–3796;
(h) Gupta, P.; Kumar, P. Eur. J. Org. Chem. 2008, 1195–1202; (i) Pandey, S. K.;
Pandey, M.; Kumar, P. Tetrahedron Lett. 2008, 49, 3297–3299.
7. (a) Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Science 1997, 277,
936–938; (b) Schaus, S. E.; Brandes, B. D.; Larrow, J. F.; Tokunaga, M.; Hansen, K.
B.; Gould, A. E.; Furrow, M. E.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 1307–
1315.
8. Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M. Bull. Chem. Soc. Jpn.
1979, 52, 1989–1993.
9. For reviews on ring-closing metathesis see: (a) Grubbs, R. H.; Chang, S.
Tetrahedron 1998, 54, 4413–4450; (b) Prunet, J. Angew. Chem., Int. Ed. 2003, 42,
2826–2830.
MEMO
OH
MEMO
O
22
21
O
f
O
HO
O
1a
Scheme 4. Reagents and conditions: (a) 2,4,6-trichlorobenzoyl chloride, DMAP,
Et3N, THF, 0 °C–rt, 20 h, 89%; (b) TBAF, THF, 6 h, 75%; (c) (PCy3)2 Ru(Cl)2 = CH–Ph
(20 mol %), CH2Cl2, reflux, 14 h, 82%; (d) 10% Pd/C, H2 (balloon), ethanol, rt, 90%, 2 h;
(e) DMP, CH2Cl2, rt, 80%, 1 h; (f) TiCl4, CH2Cl2, 0 °C–rt, 30 min, 78%.
10. For various application of HKR in synthesis of bioactive compounds, see
review: (a) Kumar, P.; Naidu, S. V.; Gupta, P. Tetrahedron 2007, 63, 2745–2785;
Account (b) Kumar, P.; Gupta, P. Synlett 2009, 1367–1382.
11. (a) Nicolaou, K. C.; Webber, S. E. Synthesis 1986, 453–461; (b) Takao, K.; Ochiai,
H.; Yoshida, K.; Hashizuka, T.; Koshimura, H.; Tadano, K.; Ogawa, S. J. Org.
Chem. 1995, 60, 8179–8193.
12. Alcaraz, L.; Harnett, J. J.; Mioskowski, C.; Martel, J. P.; Le Gall, T.; Dong-Soo, S.;
Falck, J. R. Tetrahedron Lett. 1994, 35, 5449–5452.
13. For reviews on the Swern oxidation, see: (a) Tidwell, T. T. Synthesis 1990, 857–
870; (b) Tidwell, T. T. Org. React. 1990, 39, 297–572.
intermolecular Yamaguchi esterification protocol to afford the
diene ester 1715 in 89% yield. Ring-closing metathesis of 17 under
various conditions using Grubbs’ 1st and 2nd generation catalysts
failed to provide the required 10-membered lactone 18. In order
to circumvent the problem, we thought that it would be appropri-
ate to first remove the TBDMS group and then use the ring-clos-
ing metathesis for macrocyclisation. Thus the TBDMS group of
diene 17 was removed to give the alcohol 19 which on ring-clos-
ing metathesis by using Grubbs 1st generation catalyst furnished
the cyclised product 20 as a mixture of E/Z isomers in 82% yield.
Compound 20 was subjected to hydrogenation using 10% Pd/C to
give 2115 in 90% yield, which was oxidised using Dess–Martin
periodinane (DMP) to afford compound 22 in 80% yield. Finally
removal of the MEM group using TiCl4 afforded the target
14. Ulrike, K.; Schmidt, R. R. Synthesis 1985, 1060–1061.
15. Spectral data of 16: IR (CHCl3):
m 3310, 3078, 2856, 1714, 1642, 1515, 1361,
1091, 939, 837, 776 cmꢀ1 1H NMR (CDCl3, 200 MHz): d 5.82–5.73 (m, 1H),
;
5.09–5.06 (m, 2H), 4.20–4.16 (m, 1H), 2.53–2.43 (m, 2H), 2.30–2.28 (m, 2H),
0.87 (s, 9H), 0.08 (s, 3H), 0.06 (s, 3H); 13C NMR (CDCl3, 50 MHz): d 177.2, 133.7,
118.1, 68.9, 41.9, 41.7, 25.7, 17.9,
(244.403): C, 58.97; H, 9.90. Found: C, 58.82; H, 10.08. Spectral data of 17:
¼ ꢀ36:17 (c 3.19, CHCl3), IR (CHCl3): 2926, 2855, 1735, 1647, 1463,
1258, 1096, 837, 759 cmꢀ1 1H NMR (CDCl3, 200 MHz): d 5.89–5.55 (m, 2H),
- 4.5, -4.9; Anal. Calcd for C12H24O3Si
½
a 2D5
ꢁ
m
;
5.28–5.05 (m, 4H), 5.02–4.91 (m, 1H), 4.80–4.71 (m, 1H), 4.63–4.56 (m, 1H),
4.24- 4.00 (m, 2H), 3.83–3.67 (m, 1H), 3.65–3.58 (m, 1H), 3.55- 3.46 (m, 2H),
3.35 (s, 3H), 2.48–2.38 (m, 2H), 2.02–1.83 (m, 2H), 1.79–1.69 (m, 2H), 1.18 (d,
J = 6.32 Hz, 3H), 0.84 (s, 9H), 0.05 (s, 3H), 0.03 (s, 3H); 13C NMR (CDCl3,
50 MHz): d 173.4, 137.6, 134.2, 127.9, 117.6, 92.7, 74.2, 71.7, 68.7, 67.8, 58.9,
42.1, 41.9, 41.8, 25.7, 20.6, 17.9, -4.6, -4.8; Anal. Calcd for C22H42O6Si
(430.651): C, 61.36; H, 9.83. Found: C, 61.19; H, 9.97; Spectral data of 21:
compound 1a in 78% yield. ½a D25
¼ ꢀ152:4 (c 0.1, MeOH) [Ref. 5
ꢁ
½
a 2D3
ꢁ
¼ ꢀ154:0 (c 0.1, MeOH)]. The physical and spectroscopic
data of 1a were in full agreement with the literature data
(Scheme 4).5
a 2D5
ꢁ
¼ ꢀ32:92 (c 0.40, CHCl3), IR (CHCl3):
m 3459, 3015, 2932, 1729, 1462,
In conclusion, a convergent and efficient total synthesis of deca-
restrictine J with high enantioselectivities has been accomplished
in which the stereocentres were generated by means of iterative
Jacobsen’s hydrolytic kinetic resolution, and cyclisation was
achieved by ring-closing metathesis. This approach could be used
for the synthesis of other members of decarestrictine family for
½
1378, 1253, 1179, 1042 cmꢀ1 1H NMR (CDCl3, 200 MHz): d 5.11–5.02 (m, 1H),
;
4.75–4.63 (m, 2H), 4.08–3.89 (m, 1H), 3.76–3.66 (m, 2H), 3.63–3.56 (m, 1H),
3.53–3.49 (m, 2H), 3.36 (s, 3H), 2.44–2.35 (m, 2H), 1.88–1.63 (m, 2H), 1.61–
1.34 (m, 6H), 1.24 (d, J = 6.19 Hz, 3H); 13C NMR (CDCl3, 50 MHz): d 172.7, 94.7,
71.7, 68.4, 67.9, 67.3, 59.0, 42.1, 40.4, 36.4, 27.1, 20.6, 9.06; Anal. Calcd for
C14H26O6 (290.353): C, 57.91; H, 9.03. Found: C, 57.95; H, 9.19.