Total syntheses of schulzeines B and C

Article abstract of DOI:10.1021/jo070560h

(Chemical Equation Presented) Schulzeines B (2) and C (3) were synthesized by a convergent strategy using epimeric tricyclic lactam building blocks, 4 and 5, and the C28 fatty acid side chain 6. Syntheses of tricyclic lactams (4/5) were achieved by Bischl

Full text of DOI:10.1021/jo070560h

Total Syntheses of Schulzeines B and C
Mukund K. Gurjar,* Chinmoy Pramanik,
Debabrata Bhattasali, C. V. Ramana, and
Debendra K. Mohapatra
National Chemical Laboratory, Dr. Homi Bhabha Road,
Pune - 411 008, India
mk.gurjar@ncl.res.in
ReceiVed March 22, 2007
FIGURE 1. Schulzeines B and C
through a convergent strategy that features the Bischler-
Napieralski reaction4 to construct the key tetrahydroisoquinoline
moiety of these molecules.
Inspection of structures 2 and 3 reveals that they have a com-
mon C28 fatty acid side chain and are epimeric at C11b of the
tetrahydroisoquinoline unit. Retrosynthetically, we sought to
address the synthesis of the tetrahydroisoquinoline unit by using
the Bischler-Napieralski4 reaction followed by a nonstereose-
lective reduction of the resulting dihydroisoquinoline. A con-
vergent strategy toward the suitably protected C28 fatty acid
was envisaged by the coupling of C1′-C15′ (18) and C16′-
C28′ (22) building blocks via a HWE-reaction. The resulting
enone en route should additionally provide access to the C14′-
OH group. Our plan for the synthesis of C16′-C28′ subunit is
founded upon the Sharpless asymmetric dihydroxylation.
The synthesis began with the EDC-HOBt-mediated coupling
reaction between 75 and 86 to afford the amide derivative 9 in
84% yield (Scheme 1). Treatment of 9 with POCl3 in CHCl3 at
70 °C afforded 10.4b Interestingly, the attempted reduction7 of
10 with NaCNBH3 and subsequent stirring with aq NaHCO3
also brought requisite cyclization resulting in the tricyclic
derivatives 11 and 12 (2:3), which are separated by simple
column chromatography and characterized by 2D-NMR spectral
studies. The observed nOes between H-3 and H-11b in the
NOESY spectrum of 11 clearly indicated a cis-relationship.
Following a sequence of simple protecting group manipulations,
Schulzeines B (2) and C (3) were synthesized by a
convergent strategy using epimeric tricyclic lactam building
blocks, 4 and 5, and the C28 fatty acid side chain 6.
Syntheses of tricyclic lactams (4/5) were achieved by
Bischler-Napieralski reaction. Sharpless asymmetric dihy-
droxylation and BINAL-H-mediated asymmetric reduction
of an enone was employed to prepare the key fatty acid side
chain 6. The spectral as well as analytical data of 2 and 3
were in good agreement with the reported data for the natural
products, thus confirming their assigned structures.
In 2004, Fusetani and co-workers isolated three novel
tetrahydroisoquinoline alkaloids designated schulzeines A-C
(1-3) from a bioassay-guided isolation of hydrophilic extract
of marine sponge Penares schulzei which inhibit yeast R-glu-
cosidase at concentrations as low as 48 nM.1 The constitution
and the relative stereochemistry of schluzeines were elucidated
by chemical degradation and by extensive 2D-NMR studies and
the absolute configuration by application of Mosher method.
Schluzeines encompass the 9,11-tetrahydroisoquinoline constel-
lation and are characterized by a fused δ-lactam ring and a C28
sulfated fatty acid side chain linked via an amide bond.2 The
structural complexity and important biological activity of
schulzeines A-C drew our attention with regards to their total
synthesis. Apart from a recent synthesis of the tetrahydroiso-
quinoline subunit, no report has yet appeared on the total
synthesis of any of these natural products.3 Herein, we report
the total syntheses of schulzeines B (2) and C (3) (Figure 1)
(3) Kuntiyong, P.; Akkarasamiyo, S.; Eksinitkun, G. Chem. Lett. 2006,
35, 1008.
(4) (a) Bischler, A.; Napieralski, B. In Chem. Ber. 1893, 1903. (b)
Kametani, T.; Sugahara, T.; Fukumoto, K. Tetrahedron 1971, 27, 5367.
(c) Banwell, M. G.; Cowden, C. J.; Mackay, M. F. J. Chem. Soc., Chem.
Commun. 1994, 61. (d) Angle, S. R.; Boyce, J. P. Tetrahedron Lett. 1995,
36, 6185.
(5) (a) Zhao, H.; Neamati, N.; Mazumder, A.; Sunder, S.; Pommier, Y.;
Burke, T. R., Jr. J. Med. Chem. 1997, 40, 1186. (b) Itoh, M.; Nojima, H.;
Notani, J.; Hagiwara, D.; Takai, K. Bull. Chem. Soc. Jpn. 1978, 51, 3320.
(6) (a) Nefkens, G. H. L.; Nivard, J. F. Recl. TraV. Chim. Pays Bas.
1964, 83, 199. (b) Shirude, P. S.; Kumar, V. A.; Ganesh, K. N. Tetrahedron
2004, 60, 9485.
(1) Takada, K.; Uehara, T.; Nakao, Y.; Matsunaga, S.; Van Soest, R.
W. M.; Fusetani, N. J. Am. Chem. Soc. 2004, 126, 187.
(2) (a) Burgoyne, D. L.; Miao, S.; Pathirana, C.; Andersen, R. J.; Ayer,
W. A.; Singer, P. P.; Kokke, W. C. M. C.; Ross, D. M. Can. J. Chem.
1991, 69, 20. (b) Ohba, M.; Nishimura, Y.; Kato, M.; Fujii, T. Tetrahedron
1999, 55, 4999. (c) Nakao, Y.; Maki, T.; Matsunaga, S.; Van, Soest, R. W.
M.; Fusetani, N. Tetrahedron 2000, 56, 8977.
(7) Zio´lkowski, M; Czarnocki, Z.; Leniewski, A.; Maurin, J. K.
Tetrahedron Asymmetry 1999, 10, 3371.
10.1021/jo070560h CCC: $37.00 © 2007 American Chemical Society
Published on Web 07/14/2007
J. Org. Chem. 2007, 72, 6591-6594
6591

SCHEME 1. Synthesis of 4 and Its 11-epi-Diastereomer 5
SCHEME 2. Synthesis of C28 Fatty Acid 6
11 and 12 were transformed to requisite amines 4 and 5,
respectively.
The construction of the C28 fatty acid side chain began with
the syntheses of the C15 and C13 subunits. Following the
available literature protocol,8 commercially available 1,12-
dodecanedicarboxylic acid (15) was converted to the acid 16,
and subjected to acid-catalyzed esterification to afford the methyl
ester 17. Treatment of 17 with lithiated methyldimethylphos-
phonate provided the requisite C15 subunit 18 in excellent yield
(Scheme 2).9 Synthesis of the C13 subunit started with the two-
carbon homologation of undecan-1-al (19)10 using ethoxycar-
(9) (a) Roush, W. R.; Warmus, J. S.; Works, A. B. Tetrahedron Lett.
1993, 34, 4427. (b) Fu¨rstner, A.; Baumgartner, J. Tetrahedron 1993, 49,
8541.
(8) (a) Emde, U.; Koert, U. Eur. J. Org. Chem. 2000, 1889. (b) Takahashi,
T.; Ido, T.; Iwata, R. Appl. Radiat. Isotopes 1991, 42, 801.
6592 J. Org. Chem., Vol. 72, No. 17, 2007

SCHEME 3. Synthesis of Schulzeines B (2) and C (3)
bonyl-methylene-triphenylphosphorane in CH2Cl2, affording 20
as a mixture of E/Z-isomers (85:15). Asymmetric dihydroxy-
lation of 20E using (DHQ)2PHAL, K3Fe(CN)6, K2CO3, MeSO2-
was established by application of Mosher method.14 In order to
avoid the use of (S)-(-)-BINAL-H, which is required in
stoichiometric quantities, the reduction of enone 23 was
attempted under Luche’s conditions15 to afford a 2:3 mixture
of 24 and its epimer 25. Interestingly, when the aforementioned
ketone reduction was attempted with K-Selectride,16 the dias-
tereoselectivity was reversed, and the undesired diastereomer
25 was obtained as the major product. Protection of the free
hydroxyl group in 24 as its MOM ether followed by hydro-
genolysis gave 26 in 78% over the two steps. Oxidation of 26
to the corresponding aldehyde with IBX followed by further
t
NH2, and K2OsO4·2H2O in BuOH:H2O (1:1) at 0 °C for 6 h
gave the dihydroxy derivative 21 in 85% yield.10,11 Protection
of 21 as an isopropylidene derivative followed by controlled
reduction with DIBAL-H gave the C13 aldehyde 22.
With both the C15 and C13 subunits in hand, we addressed
the HWE coupling which would provide the side chain fatty
acid unit. After exploring a variety of bases, we concluded that
the key HWE-reaction between 18 and 22 can be successfully
carried out using DBU-LiCl12 and resulted exclusively with
t
oxidation with NaClO2 in BuOH at 0 °C gave the C28 fatty
1
acid 6.With all three required fragments 4-6 now available,
their assembly into the target molecules 2 and 3 became our
next task. EDC-HOBt-mediated coupling of amine 4 with the
free carboxylic acid 6, was facile and afforded the coupled
product 27. TMSI17 mediated deprotection of the acetonide and
MOM-protecting groups in 27 gave the triol 28 in 47% yield.
To this end, persulfation of triol 28 using SO3‚Py in DMF18
followed by debenzylation afforded schulzeine B (2) in 80%
yield over two steps. Similarly, starting with 5 and following a
same sequence of reactions, the synthesis of schulzeine C (3)
was completed. The spectral as well as the analytical data of
formation of enone 23 with E-configuration. In the H NMR
spectrum of 23, the olefinic protons appeared at δ 6.36 and δ
6.70 as doublet of doublets (J15,16 ) 15.8 Hz) thus confirming
the assigned E-configuration. The resulting enone 23 was
reduced with (S)-(-)-BINAL-H in THF at -78 °C to afford
24 and its (14′R)-isomer 25 in 11:1 ratio.13 The absolute
configuration of the newly created center in major isomer 24
(10) Nakayama, K.; Kawato, H. C.; Inagaki, H.; Nakajima, R.; Kitamura,
A.; Someya, K.; Ohta, T. Org. Lett. 2000, 2, 977.
(11) (a) Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.;
Hartung, J.; Jeong, K.-S.; Kwong, H. L.; Morikawa, K.; Wang, Z. M.; Xu
D.; Zhang. X. L. J. Org. Chem. 1992, 57, 2768. (b) Kolb, H. C.;
VanNieuwenhze, M. S.; Sharpless. K. B. Chem. ReV. 1994, 94, 2483.
(12) (a) Wadsworth, W. S.; Emmons, W. D. J. Am. Chem. Soc. 1961,
83, 1733. (b) Blanchette, M. A.; Choy, W.; Davis, J. T.; Essenfeld, A. P.;
Masamune, S.; Rousch, W. R.; Sakai, T. Tetrahedron Lett. 1984, 25, 2183.
(c) Ishigami, K.; Motoyoshi, H.; Kitahara, T. Tetrahedron Lett. 2000, 41,
8897.
(13) (a) Noyori, R.; Tomino, I.; Tamimoto, Y.; Nishizawa, M. J. Am.
Chem. Soc. 1984, 106, 6709. (b) Sunazuka, T.; Shirahata, T.; Yoshida, K.;
Yamamoto, D.; Harigaya, Y.; Nagai, T.; Kiyohara, H.; Yamada, H.;
Kuwajima, I.; Omura, S. Tetrahedron Lett. 2002, 43, 1265. (c) Shirahata,
T.; Sunazuka, T.; Yoshida, K.; Yamamoto, D.; Harigaya, Y.; Nagai, T.;
Kiyohara, H.; Yamada, H.; Kuwajima, I.; Omura, S. Bioorg. Med. Chem.
Lett. 2003, 13, 937. (d) Shirahata, T.; Sunazuka, T.; Yoshida, K.; Yamamoto,
D.; Harigaya, Y.; Nagai, T.; Kiyohara, H.; Yamada, H.; Kuwajima, I.;
Omura, S. Tetrahedron 2006, 62, 9483.
(14) (a) Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512. (b)
Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem. Soc. 1991,
113, 4092.
(15) (a) Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226. (b) Luche, J.
L.; Gemal, A. L. J. Am. Chem. Soc. 1979, 101, 5848.
(16) (a) Corey, E. J.; Becker, K. B.; Varma, R. K. J. Am. Chem. Soc.
1972, 94, 8616. (b) Kim, S.; Moon, Y. C.; Ahn, K. H. J. Org. Chem. 1982,
47, 3311.
(17) (a) Jung, M. A.; Lyster, M. A. J. Org. Chem. 1977, 42, 3761. (b)
Jung, M. E.; Andrus, W. A.; Ornstein, P. L. Tetrahedron Lett. 1977, 48,
4175. (c) Hanessian, S.; Delorme, D.; Dufresne, Y. Tetrahedron. Lett. 1984,
25, 2515.
(18) (a) Lazar, L.; Csavas, M.; Borbas, A.; Gyemant, G.; Liptap, A.
ArkiVoc 2004, Vii, 196. (b) Lu, L. D.; Shie, C. R.; Kulkarni, S. S.; Pan, G.
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J. Org. Chem, Vol. 72, No. 17, 2007 6593

of NaClO2 (110 mg, 1.2 mmol) in water (1 mL). After 2 h, the
reaction mixture was diluted with water, extracted with ethyl acetate,
dried over anhydrous Na2SO4, and concentrated. The residue was
purified on silica gel by eluting with ethyl acetate and light
petroleum (1:4) to give 6 (180 mg, 88%) as light-yellow oil. [R]D
) -15.1 (c 1.1, CHCl3); IR (CHCl3) Vmax (cm-1) 3012, 2987, 2855,
synthetic 2 and 3 nicely matched with the reported data of the
natural products, thus confirming the assigned relative and
absolute stereochemistry of schulzeines B and C.
In summary, the first total syntheses of schulzeines B and C
are documented. Bischler-Napieralski reaction for the construc-
tion of key tetrahydroisoquinoline moieties, Sharpless asym-
metric dihydroxylation and BINAL-H-mediated asymmetric
reduction of an enone for the preparation of side chain C28
fatty acid, were employed. The reported approach is convergent
in nature and provides considerable flexibility for the synthesis
of related nonnatural analogues.
1
2928, 1710, 1465, 1379; H NMR (200 MHz, CDCl3): δ 4.65 (s,
2H), 3.62-3.52 (m, 3H), 3.38 (s, 3H), 2.34 (t, J ) 7.3 Hz, 2H),
1.73-1.48 (m, 10H), 1.37 (s, 6H), 1.26 (m, 34H), 0.88 (t, J ) 6.7
Hz, 3H); 13C NMR (50 MHz, CDCl3): δ 179.3, 107.8, 95.4, 81.2,
81.0, 77.6, 55.5, 34.4, 34.0, 33.0, 31.9, 29.8 (2C), 29.6 (2C), 29.4,
29.3, 29.2, 29.1, 28.8, 27.3, 26.1, 25.2, 24.7, 22.7, 14.1; MS (ESI)
m/z: Calcd for (M+ + Na) 579.47. Found: 579.19; Anal. Calcd
for C33H64O6: C, 71.18; H, 11.58. Found: C, 71.00; H, 11.75.
Schulzeine B (2). Sulfur trioxide-pyridine complex (110 mg,
0.69 mmol) was added to a solution of the 28 (20 mg, 0.023 mmol)
in dry DMF (3 mL) under nitrogen and then stirred at room tempera-
ture for 30 h. The reaction mixture was basified by adding saturated
NaHCO3 solution. After stirring for 30 min, the resulting solution
was concentrated in vacuo. The residue was triturated with ethyl
acetate and filtered. The residue was purified on a silica gel column
using methanol and ethyl acetate (1:4) to afford the sulfate salt (27
Experimental Section
Benzyl (3S,11bS)-9,11-Bis(benzyloxy)-4-oxo-2,3,4,6,7,11b-
hexahydro-1H-pyrido-[2,1-a]isoquinolin-3-ylcarbamate (11) and
Benzyl (3S,11bR)-9,11-Bis(benzyloxy)-4-oxo-2,3,4,6,7,11b-hexahy-
dro-1H-pyrido-[2,1-a]isoquinolin-3-ylcarbamate (12). A mixture
of compound 9 (3.6 g, 5.90 mmol), POCl3 (10 mL), and dry CHCl3
(10 mL) was heated under reflux for 3 h, concentrated, and co-
distilled with benzene. The residue was triturated with cold hexane
(30 mL) and decanted. The reddish gum was dissolved in glacial
acetic acid (5 mL) and methylene chloride (30 mL) and cooled to
0 °C, and then solid sodium cyanoborohydride (1.30 g, 20.68 mmol)
was added. After 1.5 h, saturated sodium bicarbonate solution was
introduced until the reaction mixture rendered basic. After 3 h of
stirring at room temperature, it was diluted with dichloromethane,
and the layers were separated. The aqueous layer was extracted
with dichloromethane (30 mL × 3). The combined layers were
washed with water, dried over Na2SO4, and evaporated, and the
orange residue was purified on silica gel column using ethyl acetate
and light petroleum (1:3) to give the cis-isomer 11 (860 mg, 26%)
as a solid; mp 130 °C, [R]D ) -82.2 (c 1.2, CHCl3); IR (CHCl3)
Vmax (cm-1): 3408, 3019, 1797, 1718, 1655, 1609, 1499, 1441,
mg, 96%). [R]D ) -24.0 (c 0.5, CH3OH); IR (Nujol) Vmax (cm-1
)
1
2923, 2853, 1631, 1464, 1378, 1221, 1109, 1090, 824; H NMR
(400MHz,CD3OD): δ7.42-7.28(m,10H),6.57(d, J)2.1Hz,1H),
6.45 (d, J ) 2.1 Hz, 1H), 5.09 (d, J ) 6.8 Hz, 2H), 5.03 (s, 2H),
4.90 (dd, J ) 11.0, 3.8 Hz, 2H), 4.65 (m, 2H), 4.59 (dd, J ) 9.7,
7.9 Hz, 1H), 4.36 (m, 1H), 2.78-2.69 (m, 3H), 2.50 (m, 1H), 2.26
(t, J ) 7.4 Hz, 2H), 2.21 (m, 1H), 1.95-1.90 (m, 2H), 1.87-1.81
(m, 1H), 1.75-1.50 (m, 10H), 1.45-1.36 (m, 3H), 1.30-1.22 (m,
30H), 0.87 (t, J ) 6.6 Hz, 3H); 13C (100 MHz, CD3OD): δ 176.1,
171.7, 159.8, 157.3, 138.6, 138.4, 138.2, 129.6, 129.4, 129.0, 128.8,
128.4, 128.3, 118.1, 107.4, 100.1, 81.1, 79.9, 78.8, 71.2, 71.0, 51.3,
49.5, 40.1, 36.9, 35.3, 32.9, 31.5, 30.8, 30.7, 30.7, 30.6, 30.5, 30.4,
30.3, 30.2, 29.7, 29.3, 26.8, 25.9, 25.8, 25.7, 24.2, 23.6, 14.4; MS
(ESI) m/z: Calcd for (M+ + Na) 1211.43. Found: 1211.48.
A solution of resulting sulfate salt (24 mg) and 10% Pd/C in
methanol (4 mL) was hydrogenated at normal temperature and
pressure for 3 h and filtered. The catalyst was washed with methanol
(2 × 2 mL), and the combined filtrate was concentrated to obtain
schulzeine B (2) (17 mg, 83%). [R]D ) -24.4 (c 0.6, CH3OH); lit.
[R]D ) -23 (c 0.1, CH3OH), IR (Nujol) Vmax (cm-1) 3416, 2923,
1
1147; H NMR (200 MHz, CDCl3): δ 7.40-7.29 (m, 15H), 6.45
(d, J ) 2.1 Hz, 1H), 6.37 (d, J ) 2.1 Hz, 1H), 6.05 (d, J ) 5.3 Hz,
1H), 5.12 (s, 2H), 5.08 (s, 2H), 4.99 (s, 2H), 4.90 (dd, J ) 10.6,
4.0 Hz, 1H), 4.75-4.69 (m, 1H), 4.36 (m, 1H), 2.89-2.40 (m, 5H),
1.48-1.34 (m, 2H); 13C (50 MHz, CDCl3): δ 170.0, 158.4, 156.0,
155.8, 137.2, 136.6, 136.4, 136.4, 128.7, 128.5, 128.4, 128.1, 128.0,
127.9, 127.4, 127.0, 117.1, 105.7, 98.9, 70.0, 66.6, 50.0, 48.7, 38.8,
29.6, 28.3, 25.5; MS (ESI) m/z: Calcd for (M+ + Na) 585.25.
Found: 585.63; Anal. Calcd for C35H34N2O5: C, 74.71; H, 6.09;
N, 4.98. Found: C, 74.93; H, 6.02; N, 4.88.
1
2853, 1628, 1460, 1376, 1220, 1063, 1002, 773; H NMR (400
MHz, CD3OD): δ 6.21 (d, J ) 2.3 Hz, 1H), 6.13 (d, J ) 2.3 Hz,
1H), 4.84 (m, 1H), 4.64 (m, 4H), 4.36 (m, 1H), 2.74-2.53 (m,
4H), 2.28 (t, J ) 7.5 Hz, 2H), 2.24 (m, 1H), 1.93 (m, 2H), 1.85
(m, 1H), 1.77-1.53 (m, 10H), 1.45-1.37 (m, 3H), 1.28 (m, 30H),
0.88 (t, J ) 6.8 Hz, 3H); 13C (100 MHz, CD3OD): δ 176.2, 171.8,
157.9, 156.1, 138.3, 115.0, 107.3, 101.9, 81.2, 80.0, 80.0, 51.7,
49.6, 40.4 37.0, 35.4, 31.6, 30.8, 30.7, 30.7, 30.5, 30.4, 30.3, 30.3,
Further elution gave the trans-isomer 12 (1.3 g, 39%) as a liquid,
[R]D ) +93.6 (c 1.05, CHCl3); IR (CHCl3) Vmax (cm-1) 3405, 3019,
1
1797, 1720, 1650, 1609, 1499, 1441, 1147; H NMR (200 MHz,
CDCl3): δ 7.42-7.26 (m, 15 H), 6.47 (d, J ) 2.2 Hz, 1H), 6.34
(d, J ) 2.2 Hz, 1H), 5.70 (br s, 1H), 5.09 (s, 2H), 5.02 (d, J ) 2.5
Hz, 2H), 5.00 (s, 2H), 4.96-4.87 (m, 1H), 4.77 (dd, J ) 10.9, 3.4
Hz, 1H), 4.04 (m, 1H), 3.08-3.02 (m, 1H), 2.93-2.73 (m, 1H),
2.66-2.43 (m, 3H), 1.77 (dt, J ) 13.5, 12.3 Hz, 1H), 1.54-1.34
(m, 1H); 13C (50 MHz, CDCl3): δ 168.3, 158.0, 156.6, 156.3, 137.7,
136.6, 136.4, 136.3, 128.5, 128.4, 128.4, 128.2, 127.9, 127.9, 127.7,
127.3, 126.9, 118.1, 106.0, 99.0, 70.0, 69.9, 66.4, 55.8, 52.7, 39.3,
30.4, 27.9, 27.3; MS (ESI) m/z: Calcd for (M+ + Na) 585.25.
Found: 585.63; Anal. Calcd for C35H34N2O5: C, 74.71; H, 6.09;
N, 4.98. Found: C, 74.85; H, 5.95; N, 4.76.
1
30.2, 29.8, 28.9, 26.9, 26.8, 26.0, 25.9, 23.6, 14.4; H NMR (400
MHz, pyridine-d5): δ 8.26 (d, 1H, J ) 6.85 Hz), 6.89 (d, 1H, J )
2.03 Hz), 6.61 (d, 1H, J ) 2.03 Hz), 5.79 (m, 1H), 5.47 (m, 1H),
5.25 (dd, 1H, J ) 11.0, 4.0 Hz), 5.17-5.09 (m, 2H), 5.99 (m, 1H),
2.91-2.62 (m, 4H), 2.50 (t, 2H, J ) 7.34 Hz), 2.40 (m, 1H), 2.16
(m, 2H), 1.96 (m, 1H), 1.91-1.55 (m, 10 H), 1.45 (m, 3H), 1.31-
1.22 (m, 30 H), 0.92 (t, 3H, J ) 6.8 Hz). MS (ESI) m/z: Calcd for
(M+ + Na) 1031.33. Found: 1031.71.
Acknowledgment. C.P. and D.B. thank CSIR (New Delhi)
for financial assistance in the form of a research fellowship.
(S)-16-((4S,5S)-5-Decyl-2,2-dimethyl-1,3-dioxolan-4-yl)-14-
(methoxymethoxy)hexadecanoic Acid (6). Iodoxybenzoic acid
(IBX) (140 mg, 0.5 mmol) and 26 (200 mg, 0.4 mmol) in DMSO
(4 mL) were stirred at room temperature for 3 h, diluted with H2O
(3 mL), and filtered. The filtrate was extracted with diethyl ether
(10 mL × 2), washed with NaHCO3, water, and brine, dried over
anhydrous Na2SO4, and concentrated. To the crude aldehyde (200
Supporting Information Available: Experimental procedures,
spectral and analytical data for all new compounds (9, 13-14, 17-
18, 21-30, and 3) and representative 1H and 13C spectra of (2-3,
6, 9, 11-14, 17-18, 21, and 23-30) and NOESY (11-12). This
material is available for free of charge via the Internet at
http://pubs.acs.org.
t
mg, 0.4 mmol), BuOH (2 mL), NaH2PO4·2H2O (190 mg, 1.2
mmol), 2-methyl-2-butene (0.2 mL) was added dropwise a solution
JO070560H
6594 J. Org. Chem., Vol. 72, No. 17, 2007