The furan approach to oxacycles. Part 4: A synthesis of (+)-decarestrictine L

Article abstract of DOI:10.1016/j.tetlet.2005.12.055

We describe an efficient new approach for the enantioselective synthesis of (+)-(2R,3S,6R)-decarestrictine L from commercially available starting material using our newly developed methodology based on the oxidation of a furan ring with singlet oxygen fol

Full text of DOI:10.1016/j.tetlet.2005.12.055

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1333–1335
The furan approach to oxacycles. Part 4: A synthesis of
(+)-decarestrictine L
*
´
´
´
Isela Garcıa, Generosa Gomez, Marta Teijeira, Carmen Teran and Yagamare Fall
Departamento de Quı´mica Orga´nica, Facultad de Quı´mica, Universidad de Vigo, 36200 Vigo, Spain
Received 22 November 2005; revised 5 December 2005; accepted 9 December 2005
Available online 28 December 2005
Abstract—We describe an efficient new approach for the enantioselective synthesis of (+)-(2R,3S,6R)-decarestrictine L from com-
mercially available starting material using our newly developed methodology based on the oxidation of a furan ring with singlet
oxygen followed by an intramolecular hetero Michael addition.
Ó 2005 Elsevier Ltd. All rights reserved.
Decarestrictine L is a minor component of the decare-
strictine family and was first isolated in 19921 from a
culture of Penicillium simplicissimus. While the major
components of the decarestrictine family show a 10-
membered lactone ring system, decarestrictine L is
unique in possessing a tetrahydropyranyl nucleus (Fig. 1).
good total syntheses of decarestrictine L can be found in
the literature.3 We recently described a new method-
ology for the synthesis of oxacyclic compounds using
either methoxyallene4a,e or furan4b,d as a starting mate-
rial. The scope and limitations of this very powerful
methodology are being determined and its application
to the synthesis of cyclic as well as polycyclic natural
products is currently under way in our laboratories.
We report herein a synthesis of (+)-decarestrictine L
using the furan approach.4b,d Furan 1 was chosen as a
chiral starting material and was synthesized according
to Scheme 1.
Decarestrictine L has been shown to inhibit HMG-CoA
reductase, involved in the first step of the biosynthesis of
cholesterol.2 The interesting biological property of this
molecule, coupled with the extreme scarcity of the natu-
ral material make it an appealing synthetic target. Some
Commercially available chiral hydroxyester 3 reacted
with TBDPSCl to give 45 in 99% yield. Hydrolysis of
ester 4 with Dibal afforded 99% yield of alcohol 55 which
was easily converted into iodide 6.5,6 Lithiation of furan
7 and reaction with 6 afforded the targeted alkylated
furan 1.7a It was anticipated that oxidation of furan 1
with singlet oxygen followed by treatment with acetic
anhydride in pyridine, would lead to butenolide 8,
direct precursor of decarestrictine L (Scheme 2).
O
Me
O
Me
O
O
HO
HO
OH
O
OH
Decarestrictine D
Decarestrictine A
O
Me
OH
O
Indeed oxidation of 1 with singlet oxygen followed by
treatment with acetic anhydride in pyridine, afforded
butenolide 85 in excellent yield (99%). Removal of the
TBDPS group of 8 with TBAF gave the bicyclic lactone
95 through an intramolecular Michael addition (72%
yield, mixture of two diastereoisomeric compounds).
Lactone 9 was opened using LiAlH4 in the presence of
BF3ÆOEt2 to afford a 95% yield of 105 as a mixture of
diastereoisomeric diols.5,4c,d Selective protection of the
primary alcohol of 10 followed by oxidation with
O
O
HO
OH
Decarestrictine L
Decarestrictine C
Figure 1.
*
Corresponding author. Fax: +34 986 81 22 62; e-mail: yagamare@
uvigo.es
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.12.055

1334
I. Garcı´a et al. / Tetrahedron Letters 47 (2006) 1333–1335
OTBDPS
OH
OTBDPS
OH
i
ii
CO2Et
CO2Et
3
5
4
[α]D = -3.53 (c 0.026, MeOH)
[α]D = -4.05 (c 0.031, MeOH)
OTBDPS
7
O
iv
iii
O
1
OTBDPS
I
6
[α]D = + 0.5 (c 0.012, MeOH)
[α]D = + 3.49 (c 0.026, MeOH)
Scheme 1. Reagents and conditions: (i) TBDPSCl, Imid, DMF (99%); (ii) Dibal, CH2Cl2, ꢀ78 °C (99%); (iii) PPh3, I2, Imid, THF, 0 °C (93%); (iv) 7,
bipy, nBuLi, THF, 0 °C to rt (99%).
H
O
ii
i
O
O
O
O
O
OMe
OMe
1
OTBDPS
OTBDPS
8
9
OH
iii
O
iv
O
10
OH
O
OTBS
11
OH
OH
+
v
O
OTBS
O
OTBS
13
12
[α]D = -1.53 (c 0.020, MeOH)
vi
OH
OTBDPS
OTBDPS
OH
viii
3
vii
6
2
O
O
O
14
2
15
O
O
[α]D = +18.94 (c 0.016, MeOH)
[α]D = +11.61 (c 0.018, MeOH)
Scheme 2. Reagents and conditions: (i) (a) 1O2, MeOH, rose bengal, hm; (b) Ac2O, py, DMAP (96%, two steps); (ii) TBAF, THF, rt (72%); (iii) LAH,
BF3ÆOEt2 (95%); (iv) (a) TBSCl, Imid, THF (91%); (b) TPAP, NMO, CH2Cl2 (83%); (v) NaBH4, MeOH–CH2Cl2, ꢀ78 °C (97% 12/13: 4.5/5.5); (vi)
(a) TBDPSCl, Imid, DMF (80%); (b) CSA, CH2Cl2/MeOH (1:1), 0 °C (90%); (vii) (a) TPAP, NMO, CH2Cl2 (90%); (b) MeLi, Et2O, ꢀ78 °C (99%);
(c) TPAP, NMO, CH2Cl2 (91%); (viii) TBAF, THF, rt (82%).
tetrapropylammonium perruthenate (TPAP) afforded a
mixture of two diastereoisomeric ketones 11,5 which
on reaction with sodium borohydride in MeOH–CH2Cl2
at ꢀ78 °C gave a mixture of two diastereoisomeric alco-
hols 127b [Rf: 0.49 (50% EtOAc/hexane)] and 13.7c
[Rf: 0.59 (50% EtOAc/hexane), total yield 97%,
12/13 = 4.5/5.5] easily separable by column chromato-
graphy using 10% EtOAc/hexane as eluent. The relative
stereochemistry of 13 was established by NOE experi-
ments (Fig. 2).
Protection of the secondary alcohol of 13 and selective
removal of the TBS group afforded alcohol 14. TPAP
oxidation of alcohol 14 followed by reaction of the
resulting aldehyde with MeLi afforded a secondary alco-
hol which was oxidized to ketone 15.7d The stage was set

I. Garcı´a et al. / Tetrahedron Letters 47 (2006) 1333–1335
1335
Iwabuchi, Y.; Irie, H.; Hatakeyama, S. Heterocycles 2000,
52, 525–528; (f) Lukesh, J. M.; Donaldson, W. A. Tetra-
hedron: Asymmetry 2003, 14, 757–762.
6.8%
H
OH
8.1%
´
´
4. (a) Fall, Y.; Gomez, G.; Fernandez, C. Tetrahedron Lett.
H
1999, 40, 8307–8308; (b) Fall, Y.; Vidal, B.; Alonso, D.;
H3C
1.1%
O
OTBS
´
Gomez, G. Tetrahedron Lett. 2003, 44, 4467–4469; (c)
H
0.5%
´
´
´
Perez, M.; Canoa, P.; Gomez, G.; Teran, C.; Fall, Y.
Tetrahedron Lett. 2004, 45, 5207–5209; (d) Alonso, D.;
´
´
Perez, M.; Gomez, G.; Covelo, B.; Fall, Y. Tetrahedron
13
´
´
2005, 61, 2021–2026; (e) Perez, M.; Canoa, P.; Gomez, G.;
Teijeira, M.; Fall, Y. Synthesis 2005, 411–414.
5. All new compounds exhibited satisfactory 1H and 13C
NMR, analytical, and/or high resolution mass spectral
data.
Figure 2. NOE correlations for 13.
for the final TBAF deprotection step which afforded
(+)-decarestrictine L (2) which was spectroscopically
identical to the natural product.1,3f
´
6. Perez-Sestelo, J.; Mascarenas, J. L.; Castedo, L.; Mourino,
˜
˜
A. J. Org. Chem. 1993, 58, 118–123.
25
7. (a) Compound 1: ½aꢁD +0.5 (c 0.012, MeOH); 1H NMR
(400 MHz, CDCl3), d: 7.70 (4H, d, J = 6.94), 7.46–7.40
(6H, m), 7.39–7.33 (1H, m), 6.25 (1H, dd, J = 2.04, 2.84),
5.88 (1H, d, J = 2.84), 3.94 (1H, q, J = 5.93), 2.72–2.66
(2H, m), 1.87–1.77 (2H, m), 1.10 (3H, d, J = 6.14),
1.08 (9H, s); 13C NMR (100 MHz, CDCl3), d: 156.23 (C),
140.64 (CH), 135.86 (CH), 134.76 (C), 129.50 (CH), 127.50
(CH), 110.00 (CH), 104.44 (CH), 68.87 (CH), 37.46 (CH2),
27.02 (CH3-tBu), 23.81 (CH3), 23.12 (CH2), 19.29 (C-tBu);
HRMS (FAB+) calcd for C24H29O2Si 377.1937, found
377.1951; (b) Compound 12: 1H NMR (400 MHz, CDCl3),
d: 3.92 (1H, s), 3.85–3.80 (1H, m), 3.76–3.70 (1H, m), 3.39
(1H, m), 3.32–3.27 (1H, m), 3.16–3.11 (1H, m), 2.08–2.05
(1H, m), 1.89–1.83 (2H, m), 1.67 (1H, m), 1.47–1.18 (2H,
m), 1.14 (3H, d, J = 5.98), 0.89 (9H, s), 0.07 (6H, s); 13C
NMR (100 MHz, CDCl3), d: 81.15 (CH), 73.44 (CH), 70.21
(CH), 60.38 (CH2), 37.59 (CH2), 32.90 (CH2), 32.09 (CH2),
25.84 (CH3-tBu), 21.46 (CH3), 18.21 (C-tBu), ꢀ5.47
(CH3Si), ꢀ5.55 (CH3Si); HRMS (FAB+) calcd for
C14H31O3Si 275.2042, found 275.2049; (c) Compound 13:
1H NMR (400 MHz, CDCl3), d: 3.91–3.85 (2H, m), 3.79–
3.45 (3H, m), 2.80 (1H, s), 1.95–1.84 (2H, m), 1.83–1.76
(1H, m), 1.75–1.64 (1H, m), 1.60–1.53 (1H, m), 1.40–
1.24 (1H, m), 1.17 (3H, d, J = 6.52), 0.89 (9H, s), 0.06 (6H,
s); 13C NMR (100 MHz, CDCl3), d: 74.25 (CH), 67.19
(CH), 66.88 (CH), 60.19 (CH2), 32.34 (CH2), 27.88 (CH2),
26.57 (CH2), 26.26 (CH3-tBu), 18.84 (CH4), 18.24 (C-tBu),
ꢀ5.46 (CH3Si); HRMS (FAB+) calcd for C14H31O3Si
In conclusion, a new and efficient method for the enan-
tioselective synthesis of (+)-decarestrictine L (2) from
commercially available chiral hydroxyester
3
is
described. This synthesis enlarges the scope of our newly
developed methodology for the synthesis of oxacyclic
systems. The use of this methodology for the synthesis
of various natural products is now under way in our
laboratories.
Acknowledgements
This work was supported by a grant from the Xunta de
Galicia (PGIDIT04BTF301031PR). We also thank the
NMR service of the CACTI, University of Vigo, for
NMR studies. M.T. thanks the Xunta de Galicia for a
Parga Pondal contract.
References and notes
1. Grabley, S.; Hammann, P.; Huetter, K.; Kirsch, R.; Kluge,
H.; Thiericke, R.; Mayer, M.; Zeeck, A. J. Antibiot. 1992,
45, 1176.
25
275.2042, found 275.2049; (d) Compound 15: ½aꢁD
1
2. (a) Go¨hrt, A.; Zeeck, A.; Huetter, K.; Kirssch, R.; Kluge,
¨
+11.61 (c 0.018, MeOH); H NMR (400 MHz, CDCl3), d:
H.; Thiericke, R.; Mayer, M. J. Antibiot. 1992, 45, 66; (b)
Mayer, M.; Thiericke, R. J. Antibiot. 1993, 46, 1372.
3. (a) Machinaga, N.; Kibayashi, C. Tetrahedron Lett. 1993,
34, 5739–5742; (b) Clark, J. S.; Whitlock, G. A. Tetra-
hedron Lett. 1994, 35, 6381–6382; (c) Nokami, J.; Tanigu-
7.66–7.62 (4H, m), 7.42–7.35 (6H, m), 4.25 (1H, m), 3.92
(1H, m), 3.64 (1H, m), 2.91 (1H, dd, J = 4.05, 15.13), 2.73
(1H, dd, J = 10.42, 15.09), 2.11 (3H, s), 1.60–1.58 (4H,
m), 1.04 (9H, s), 0.99 (3H, d, J = 6.13); 13C NMR (100
MHz, CDCl3), d: 207.84 (CO), 135.71, 135.69, 133.97,
129.90, 129.77, 127.79, 127.62, 72.75 (CH), 69.06 (CH),
65.03 (CH), 40.71 (CH2), 31.57 (CH2), 29.70, 27.46.77
(CH2), 26.95 (CH3-tBu), 20.89 (C-tBu), 19.15 (CH3).
´
chi, T.; Ogawa, Y. Chem. Lett. 1995, 43–44; (d) Solladie,
G.; Arce, E.; Bauder, C.; Carreno, M. C. J. Org. Chem.
˜
1998, 63, 2332–2337; (e) Esumi, T.; Kimura, R.; Mori, M.;