Total synthesis of cruentaren B

Article abstract of DOI:10.1021/jo800181n

(Chemical Equation Presented) A convergent total synthesis of the cytotoxic natural product cruentaren B is completed in 26 steps (longest linear sequence) with an overall yield of 7.1%. For the construction of the C₁-C ₁₁ benzolacto

Full text of DOI:10.1021/jo800181n

Total Synthesis of Cruentaren B
Tushar Kanti Chakraborty* and Amit Kumar Chattopadhyay
Indian Institute of Chemical Technology,
Hyderabad 500007, India
chakraborty@iict.res.in
ReceiVed January 23, 2008
FIGURE 1. Structures of cruentarens.
SCHEME 1. Retrosynthetic Analysis of Cruentaren B (2)
A convergent total synthesis of the cytotoxic natural product
cruentaren B is completed in 26 steps (longest linear
sequence) with an overall yield of 7.1%. For the construction
of the C1-C11 benzolactone fragment of the molecule, the
key steps used were O-methylation, using a Mitsunobu
reaction, a Stille coupling method to construct the C7-C8
bond, and a Brown’s asymmetric crotylboration reaction for
the direct enantioselective installation of the two chiral
centers present in this fragment. For diastereoselective
installation of the chiral centers in the C12-C20 polyketide
fragment, an Evans syn aldol reaction on a chiral aldehyde,
derived from methyl (R)-3-hydroxyl-2-methylpropionate, and
subsequently a Mukaiyama aldol reaction were employed.
For the construction of the C21-C28 tail, a “non-Evans” syn
aldol reaction was used. The three fragments were coupled
by an SN2 reaction and a Wittig olefination reaction followed
by standard functional group manipulations to furnish the
target molecule.
filamentous fungi and showed high cytotoxicity against L929
mouse fibroblast cells, cruentaren B showed only marginal
cytotoxicity and no antifungal activity.4 However, thorough
evaluation of other biological properties of cruentarens and their
analogues can only be undertaken if a versatile synthetic route
is devised for their syntheses. Because of their novel structures
and wide-ranging biological activities,5 cruentarens have at-
tracted the attention of synthetic chemists worldwide. Synthesis
of cruentaren A has been achieved by Maier et al.6,7 and also
by Fürstner’s group.8 In this paper, we describe a convergent
total synthesis of cruentaren B.
A retrosynthetic analysis of cruentaren B (2) is shown in
Scheme 1. We envisioned constructing the target molecule from
the fragments 4–6 via an acetylide-triflate cross-coupling
reaction (4 + 5), followed by selective hydrogenation to the
Z-olefin and a Wittig olefination with 6. The resulting product
3 after global deprotection of the protecting groups and a base-
catalyzed cyclization was expected to furnish the target natural
product 2. While compound 4 could be built from 2,4,6-
In search of new biologically active natural products, myxo-
bacteria have been proven to be a rich repertoire of innumerable
secondary metabolites with novel structures and wide-ranging
properties.1,2 The benzolactones, cruentaren A (1) and its ring-
contracted congener cruentaren B (2) (Figure 1), are two such
molecules isolated from myxobacterium ByssoVorax cruenta.3,4
While cruentaren A strongly inhibited the growth of yeasts and
(1) Reichenbach, H. J. Ind. Microb. Biotechnol. 2001, 27, 149–156.
(2) Reichenbach, H.; Höfle, G. In Drug DiscoVery from Nature; Grabley,
S., Thiericke, R., Eds.; Springer: Berlin, Germany, 1999; pp149–179..
(3) Kunze, B.; Steinmetz, H.; Höfle, G.; Huss, M.; Wieczorek, H.; Reichen-
bach, H. J. Antibiot. 2006, 59, 664–668.
(5) Kunze, B.; Sasse, F.; Wieczorek, H.; Huss, M. FEBS Lett. 2007, 581,
3523–3527.
(6) Vintonyak, V. V.; Maier, M. E. Org. Lett. 2007, 9, 655–658.
(7) Vintonyak, V. V.; Maier, M. E. Angew. Chem., Int. Ed. 2007, 46, 5209–
5211.
(4) Jundt, L.; Steinmetz, H.; Luger, P.; Weber, M.; Kunze, B.; Reichenbach,
H.; Höfle, G. Eur. J. Org. Chem. 2006, 5036–5044.
(8) Fürstner, A.; Bindl, M.; Jean, L. Angew. Chem., Int. Ed. 2007, 46, 9275–
9278.
3578 J. Org. Chem. 2008, 73, 3578–3581
10.1021/jo800181n CCC: $40.75 2008 American Chemical Society
Published on Web 03/26/2008

SCHEME 2. Synthesis of Fragment 4a
SCHEME 3. Synthesis of Fragment 5a
a Reagents and conditions: (a) DIAD, MeOH, Ph3P, THF, 0 °C, 98%;
(b) Tf2O, pyridine, 0 °C, 90%; (c) Bu3Sn(allyl), LiCl, TFP, Pd2(dba)3, NMP,
rt, 72%; (d) OsO4, NMO, acetone:water (1:1), rt, 92%; (e) NaIO4, THF:
H2O (1:1), 0 °C, 93%; (f) (-)-Ipc2BOMe, trans-but-2-ene, KOtBu, n-BuLi,
BF3 ·Et2O, THF:Et2O (10:1), -78 to 0 °C, 89%; (g) TBSOTf, DIPEA,
CH2Cl2, 0 °C, 92%; (h) same as in footnote d, 93%; (i) same as in footnote
e, 90%; (j) NaBH4, MeOH:THF (1:1), 0 °C, 97%.
trihydroxybenzoic acid 7, the acetylenic intermediate 5 could
be derived from commercially available methyl (R)-3-hydroxyl-
2-methylpropionate (8). An enantioselective aldol reaction on
butyraldehyde 9 could furnish the ylide component 6.
Our synthesis commenced with the construction of the
benzolactone moiety 4 (Scheme 2). Selective O-methylation of
10, derived from readily available acid 7,9 using diisopropyla-
zodicarboxylate (DIAD) and methanol under Mitsunobu condi-
tions,10 gave 11 in an excellent yield of 98%.
Next, the alcohol 11 was treated with Tf2O in pyridine to
give the triflate compound, which upon Pd-catalyzed Stille
coupling11 with allylstannane in the presence of LiCl and tri(2-
furyl)phosphine (TFP) in N-methylpyrrolidine (NMP) gave the
desired product 12 in 65% yield. Dihydroxylation of 12 with
N-methylmorpholine (NMO) and OsO4 followed by oxidative
cleavage with NaIO4 gave an aldehyde, which on asymme-
tric crotylboration following Brown’s protocol12 and with (-)
-isopinocamphenylborane, (-)-Ipc2B(allyl), resulted in the
formation of an anti-adduct, the homoallylic alcohol 13 in 76%
overall yield in three steps and with an ee of 97% as determined
by the Mosher ester method.13 Silyl protection of the secondary
hydroxyl group with TBSOTf and DIPEA in CH2Cl2 gave 14
in 92% yield. Compound 14 was converted to the primary
alcohol 4 in three steps in 81% overall yieldsdihydroxylation
followed by oxidative cleavage and a NaBH4 reduction.
Synthesis of 5 is depicted in Scheme 3. Aldehyde 16, prepared
from commercially available methyl (R)-3-hydroxyl-2-methyl-
propionate 8 by TBDPS protection and reduction,14 was
subjected to the Evans syn aldol reaction under modified
conditions15 with propanoyl oxazolidinone 15 to afford aldol
product 17 in good yield and diastereoselectivity (92%, de 98%)
after chromatographic purification. Silyl protection of the
secondary hydroxyl group as TBS ether with TBSOTf and
DIPEA followed by reductive removal16 of the chiral auxiliary
a Reagents and conditions: (a) TiCl4, (-)-sparteine, CH2Cl2, -78 °C,
92%; (b) TBSOTf, DIPEA, CH2Cl2, 0 °C, 94%; (c) LiBH4, ether (cat. water),
0 °C, 90%; (d) (COCl)2, DMSO, Et3N, CH2Cl2, -78 °C; (e) TBS-enol ether
of tert-butylacetate, BF3 ·Et2O, THF, -78 °C, 70% (in two steps); (f)
TBSOTf, DIPEA, CH2Cl2, 0 °C, 93%; (g) DIBAL-H, CH2Cl2, -40 °C; (h)
DMP, NaHCO3, CH2Cl2, 0 °C; (i) CBr4, Ph3P, CH2Cl2, Et3N, 0 °C to rt; (j)
n-BuLi, THF, -78 °C, 85% (in four steps); (k) TBAF, THF, 0 °C to rt,
85%; (l) TsCl, Et3N, DMAP, CH2Cl2, 0 °C, 96%; (m) NaCN, NaI (cat),
DMSO, 90 °C, 82%; (n) 2,2-dimethoxypropane, CSA, 0 °C to rt, 98%; (o)
(i) DIBAL-H, CH2Cl2, -78 °C; (ii) 3 N NaOH, -78 °C to rt; (p) NaBH4,
THF:MeOH (1:1), 0 °C, 92% (in three steps); (q) CSA, CH2Cl2:MeOH
(1:1), 0 °C, 93%; (r) TBSOTf, DIPEA, CH2Cl2, 0 °C, 91%.
gave the alcohol 19 in 85% yield in two steps. Swern oxidation17
of the alcohol 19 followed by Mukaiyama aldol18 with TBS
enol ether of tert-butyl acetate gave the required diastereomer
20 in 70% yield in two steps and diastereoselectivity of 81%
after column chromatographic purification.
Protection of the secondary hydroxyl group of 20 as TBS
ether followed by DIBAL-H reduction gave the alcohol 22. The
Dess-Martin periodinane (DMP) oxidation19 of 22 gave an
aldehyde, which was converted to the alkyne compound 23 by
using Corey’s protocol20 (85% over four steps). Global depro-
tection of the silyl protecting groups was followed by selective
monotosylation of the primary hydroxyl group and cyanation
with NaCN in the presence of a catalytic amount of NaI at 90
°C in DMSO to give the cyano compound 25 in 67% yield in
three steps. Acetonide protection followed by DIBAL-H reduc-
tion,21 hydrolysis, and finally NaBH4 reduction gave the alcohol
27 in 90% yield in four steps. Next, deprotection of the acetonide
with CSA and global protection of the resulting triol with
TBSOTf afforded 5 in 85% yield over two steps.
(9) Dushin, R. G.; Danishefsky, S. J. J. Am. Chem. Soc. 1992, 114, 655–
659.
(10) (a) Dembinski, R. Eur. J. Org. Chem. 2004, 2763–2772. (b) Ahn, C.;
Correia, R.; DeShong, P J. Org. Chem. 2002, 67, 1751–1753. (c) Mitsunobu,
O. Synthesis 1981, 1–28. (d) Mitsunobu, O.; Yamada, M. Bull. Chem. Soc. Jpn.
1967, 40, 2380–2382.
(11) (a) Stille, J. K.; Groh, B. L. J. Am. Chem. Soc. 1987, 109, 813–817. (b)
Farina, V.; Krishna, B. J. Am. Chem. Soc. 1991, 113, 9585–9595. For a review
see: (c) Mitchell, T. N. Synthesis 1992, 803–815.
(12) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986, 108, 5919–5923.
(13) (a) Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512–519.
(b) Mosher, H. S.; Dull, D. L.; Dale, J. A. J. Org. Chem. 1969, 34, 2543–2549.
(14) (a) Chakraborty, T. K.; Goswami, R. K.; Sreekanth, M. Tetrahedron
Lett. 2007, 48, 4075–4078. (b) Roush, W. R.; Hoong, L. K.; Palmer, M. A. J.;
Straub, J. A.; Palkowitz, A. D. J. Org. Chem. 1990, 55, 4117–4126.
(15) Crimmins, M. T.; King, B. W.; Tabet, E. A.; Chaudhary, K. J. Org.
Chem. 2001, 66, 894–902.
(17) (a) Mancuso, A. J.; Swern, D. Synthesis 1981, 165–185. (b) Mancuso,
A. J.; Swern, D. Tetrahedron Lett. 1981, 35, 2473–2476.
(18) (a) Saigo, K.; Osaki, M.; Mukaiyama, T. Chem. Lett. 1975, 989–990.
(b) Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc. 1974, 96, 7503–
7509. (c) Mukaiyama, T.; Narasaka, K.; Banno, K. Chem. Lett. 1973, 1011–
1014.
(19) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277–7287.
(20) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 13, 3769–3772.
(21) Kabota, I.; Takamura, H.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126,
14374–14376.
(16) Penning, T. P.; Djuric, S. W.; Haack, R. A.; Kalish, V. J.; Miyashiro,
J. M.; Rowell, B. W.; Yu, S. S. Synth. Commun. 1990, 20, 307–312.
J. Org. Chem. Vol. 73, No. 9, 2008 3579

SCHEME 4. Synthesis of Fragment 6a
alcohol, which was reduced by hydrogenation by using Pd-
BaSO4/quinoline to afford the Z-olefin 35 in 88% overall yield
in two steps. Next, Dess-Martin periodinane (DMP)19 oxidation
followed by a selective Z-olefination25 furnished the entire
carbon framework 3 of the target molecule. Reaction between
the ylide, generated from 6, and aldehyde at -80 °C in
THF-HMPA gave the required Z-olefin in 64% yield on the
basis of recovered aldehyde. Exclusively, the Z-olefin was
obtained when the reaction was carried out at -80 °C. When it
was done at higher temperature (-40 to 0 °C), the E-isomer
was also formed along with the Z-olefin and the aldehyde was
unstable. Use of NaHMDS in THF gave only 5% of the required
product after 12 h of reaction at -80 °C with extensive
decomposition of the aldehyde. The product 3 was subjected
to global deprotection of the TBS groups to afford the desilylated
product, in 92% yields, which on treatment with LiOH ·H2O in
THF afforded the target molecule, cruentaren B (2), in 89%
yield. The spectral data of our synthetic product and its optical
a Reagents and conditions: (a) TiCl4, DIPEA, butanal, CH2Cl2, 0 °C,
87%; (b) TBSOTf, DIPEA, CH2Cl2, 0 °C, 94%; (c) LiOH, H2O2, THF:
H2O (3:1), 0 °C to rt, 86%; (d) EDCI, HOBt, DIPEA, 2-aminoethanol,
CH2Cl2, 0 °C to rt, 80%; (e) Ph3P, I2, imidazole, CH2Cl2, 0 °C to rt, 75%;
(f) Ph3P, 90 °C, 98%.
SCHEME 5. Coupling of Fragments 4, 5, and 6 and
Completion of the Synthesis of Cruentaren B (2)a
rotation datasfound [R]26 -9.4 (c 0.41, MeOH), reported4
D
[R]22 -9.1 (c 6.6 mg/mL, MeOH)swere virtually identical
D
with those of the natural product.
In conclusion, we have achieved the stereoselective, conver-
gent total synthesis of cruentaren B and a synthetic segment
for the cruentaren A, through longest linear sequence of 26 steps
in overall yields of 7.1%. We are now trying to cyclize the linear
framework to 12-membered cruentaren A. We believe that this
synthetic strategy can provide a practical route to many novel
cruentaren analogues that can be used for biological screenings.
a Reagents and conditions: (a) Tf2O, 2,6-lutidine, CH2Cl2, -78 °C; (b)
5, n-BuLi, HMPA, THF, then the triflate was added, -78 °C, 72%; (c)
HF·py complex, THF, rt, 90%; (d) H2, Pd-BaSO4, quinoline (0.05 equiv),
rt, 98%; (e) DMP, NaHCO3, CH2Cl2, 0 °C, 95%; (f) 6, n-BuLi, HMPA,
THF, then added the aldehyde, -78 °C, 64% (on the basis of recovered
aldehyde); (g) HF·py, THF, -40 °C to –4 °C, 92%; (h) LiOH.H2O, THF:
H2O:MeOH (3:1:1), 0 °C, 89%.
Experimental Section
Preparation of 3. To a solution of 35 (540 mg, 0.645 mmol) in
CH2Cl2 (3 mL) were added NaHCO3 (162 mg, 1.94 mmol) and
DMP (411 mg, 0.97 mmol) sequentially at 0 °C. After being stirred
for 1 h at the same temperature, the reaction mixture was quenched
by addition of saturated aqueous Na2SO3 solution and stirred for
30 min. Then it was extracted with EtOAc, washed with water and
brine, dried over anhydrous Na2SO4, and concentrated in vacuo to
dryness. The residue was chromatographed on silica gel with EtOAc
in petroleum ether (1:20) to give aldehyde (511 mg, 95%) as a
colorless oil.
To a stirred solution of 6 (1 g, 1.53 mmol) in THF (3 mL) was
added n-butyl lithium (1.6 M, 0.84 mL, 1.35 mmol) at -80 °C.
After being stirred for 30 min HMPA (0.7 mL, 3.67 mmol) followed
by aldehyde (511 mg, 0.61 mmol) in THF (1 mL) were added in
a dropwise manner to the reaction mixture at the same temperature
and the resulting solution was stirred for an additional 12 h at -80
°C. The reaction mixture was quenched with saturated aqueous
NH4Cl solution and diluted with EtOAc. The organic layer was
washed sequentially with water and brine and dried over anhydrous
Na2SO4. The extract was concentrated to dryness under vacuum
and chromatographed on silica gel with EtOAc-petroleum ether
(1:32) to give 3 (351 mg) as a colorless liquid and unreacted
aldehyde (95 mg). The yield is found to be 64% on the basis of
recovered aldehyde. Rf 0.4 (SiO2, 6% EtOAc in petroleum ether);
[R]29D + 17.4 (c 0.61, CHCl3); 1H NMR (CDCl3, 500 MHz) δ 6.50
(d, J ) 2.6 Hz, 1H), 6.36 (t, J ) 4.9 Hz, 1H), 6.31 (d, J ) 2.6 Hz,
1H), 5.54–5.45 (m, 2H), 3.98–3.91 (m, 1H), 3.91–3.84 (m, 1H),
3.82 (s, 3H), 3.76 (m, 1H), 3.70 (q, J ) 5.3 Hz, 1H), 3.55–3.48
(m, 2H), 2.71 (dd, J ) 12.1, 9.5 Hz, 1H), 2.44 (qd, J ) 6.8, 3.8
Hz, 1H), 1.75–1.55 (m, 5H), 1.70 (s, 3H), 1.67 (s, 3H), 1.41 (m,
2H), 1.08 (d, J ) 7.2, 3H), 0.92 (d, J ) 6.8 Hz, 3H), 0.91 (d, J )
The synthetic route for the right-hand segment 6 is depicted
in Scheme 4. The non-Evans syn-aldol reaction between 29 and
butanal 9 with the Crimmins protocol22 gave secondary alcohol
30. Protection of the hydroxyl group as TBS ether, followed
by oxidative removal of the chiral auxiliary with H2O2 and
LiOH23 gave 32 in 70% yield in three steps. This was identical
in all respects with the one reported earlier.7 The compound 32
was coupled with 2-aminoethanol using common amide bond
forming protocol with EDCI and HOBt to afford 33 in 80%
yield. The phosphonium salt 6 was generated in 73% yield in
two steps with conversion of the hydroxyl group to an iodo
with Ph3P, I2, and imidazole, followed by the reaction of the
iodide with Ph3P.
With all three segments 4–6 in hand, we undertook studies
to couple them together to build the entire framework of the
cruentaren B (Scheme 5). The triftate, generated from 4 with
Tf2O and 2,6-lutidine in CH2Cl2, was treated with the lithiated
alkyne24 moiety of 5 to afford the desired coupling product 34
with 72% yield.
After successful first coupling, we deprotected the primary
TBS selectively with HF-py complex to give an intermediate
(22) (a) Crimmins, M. T.; King, B. W.; Tabet, E. A J. Am. Chem. Soc. 1997,
119, 7883–7884. For some earlier leading references on oxazolidinethione-based
aldol reactions giving the “non-Evans” syn products see the following review
articles: (b) Fujita, E.; Nagao, Y. AdV. Heterocycl. Chem. 1989, 45, 1–36. (c)
Mukaiyama, T.; Kobayashi, S. Org. React. 1994, 46, 1–103.
(23) Evans, D. A.; Britton, T. C.; Ellman, J. A. Tetrahedron Lett. 1987, 28,
6141–6144.
(25) Nicolaou, K. C.; Bunnage, M. E.; McGarry, D. G.; Shi, S.; Somers,
P. K.; Wallace, P. A.; Chu, X.-J.; Agrios, K. A.; Gunzner, J. L.; Yang, Z. Chem.
Eur. J. 1999, 5, 599–617.
(24) Mori, Y.; Hayashi, H. Tetrahedron 2002, 58, 1789–1797.
3580 J. Org. Chem. Vol. 73, No. 9, 2008

7.2 Hz, 3H), 0.90 (s, 9H), 0.89 (s, 22H), 0.87 (t, J ) 4.93 Hz, 3H),
0.80 (s, 9H), 0.08 (s, 6H), 0.05 (s, 3H), 0.03 (s, 3H), 0.01 (s, 3H),
-0.43 (s, 3H); 13C NMR (CDCl3, 150 MHz) δ 173.7, 164.2, 158.9,
147.1, 132.6, 126.1, 125.8, 115.1, 104.8, 104.7, 99.8, 75.2, 74.7,
72.8, 55.5, 45.6, 40.2, 39.8, 38.0, 37.1, 36.3, 34.8, 30.3, 29.7, 28.7,
26.2, 25.9, 25.8, 25.7, 25.6, 25.6, 19.2, 18.5, 17.9, 17.9, 17.4, 14.3,
14.2, 13.0, 10.4, -3.3, -3.4, -3.9, -4.6, -4.7, -5.2; IR (neat)
2955, 2930, 2856, 1731, 1654, 1612, 1577, 1464, 1381, 1381, 1254,
1205, 1159, 1065, 1030, 835, 772 cm-1; MS (ESI) m/z (%) 1127
(100) [M + Na]+; HRMS (ESI) calcd for C60H113NO9NaSi4 [M +
Na]+ m/z 1126.7390, found 1126.7356.
on silica gel with MeOH-CHCl3 (1:20) to give 2 (16.2 mg, 89%)
as a colorless oil.
1
Rf 0.45 (SiO2, EtOAc); [R]26 -9.4 (c 0.41, MeOH); H NMR
D
(CDCl3, 400 MHz) δ 11.16 (s, 1H), 6.41 (t, J ) 4.4 Hz, 1H), 6.35
(d, J ) 2.2 Hz, 1H), 6.26(d, J ) 2.2 Hz, 1H), 5.68–5.45 (m, 4H),
4.34 (ddd, J ) 11.7, 6.6, 3.3 Hz, 1H), 3.90– 3.80 (m, 4H), 3.80 (s,
3H), 3.47 (dd, J ) 9.9, 1.5 Hz, 1H), 2.91 (dd, J ) 16.1, 11.7 Hz,
1H), 2.81 (dd, J ) 16.1, 3.3 Hz, 1H), 2.44–2.11 (m, 7H), 1.95–2.04
(m, 1H), 1.64–1.76 (m, 2H), 1.40–1.50 (m, 2H), 1.36–1.27 (m, 2H),
1.13 (d, J ) 7.3 Hz, 3H), 1.02 (d, J ) 6.9 Hz, 3H), 0.92 (d, J )
6.9 Hz, 3H), 0.84 (d, J ) 6.9 Hz, 3H), 0.91(t, J ) 7.3 Hz, 3H); 13
C
Preparation of Cruentaren B. To a stirred solution of 3 (200
mg, 0.181 mmol) in THF (2 mL) was added 70% aq HF-py
complex (1.3 mL) at -40 °C. After being stirred for 3 h, the reaction
mixture was warmed to -4 °C and stirred for an additional 20 h at
the same temperature. The reaction was quenched with saturated
aqueous NaHCO3 solution at 0 °C and extracted with EtOAc and
washed sequentially with water and brine. The organic extract was
dried over anhydrous Na2SO4 and concentrated to dryness under
vacuum. The residue was chromatographed on silica gel with
EtOAc-petroleum ether (7:10) to give tetrol (108 mg, 92%) as a
colorless liquid.
NMR (CDCl3, 100 MHz) δ 176.3, 170.0, 165.7, 164.4, 141.1, 131.4,
129.6, 127,6, 126.3, 106.3, 101.7, 99.4, 82.3, 80.2, 77.3, 71.8, 55.6,
44.8, 37.3, 37.2, 36.4, 36.1, 35.7, 33.3, 30.6, 30.0, 29.7, 19.2, 15.7,
15.0, 14.0, 11.2, 4.3; IR (neat) 3446, 2954, 2929, 2857, 1687, 1631,
1459, 1375, 1249, 1208, 1158, 760 cm-1; MS (ESI) m/z (%) 612
(100) [M + Na]+; HRMS (ESI) calcd for C33H51NO8Na [M + Na]+
m/z 612.3512, found 612.3517.
Acknowledgment. The authors wish to thank CSIR, New
Delhi for a research fellowship (A.K.C.).
To a stirred solution of the tetrol (20 mg, 0.03 mmol) in
THF-water-MeOH (3:1:1) mixture (1.5 mL) was added LiOH ·
H2O (4 mg, 0.09 mmol) at 0 °C. After being stirred for 3 h at the
same temperature, solvent was removed in vacuo and the residue
was dissolved in EtOAc. The organic layer was washed with water
and brine and dried over anhydrous Na2SO4. The organic extract
was concentrated to dryness under vacuum and chromatographed
Supporting Information Available: Experimental proce-
dures, spectral data, and copies of 1H and 13C NMR spectra for
all compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO800181N
J. Org. Chem. Vol. 73, No. 9, 2008 3581