Regioselective reductive cleavage of bis-benzylidene acetal: Stereoselective synthesis of anticancer agent OGT2378 and glycosidase inhibitor 1,4-dideoxy-1,4-imino-l-xylitol

Full text of DOI:10.1021/jo900030p

Regioselective Reductive Cleavage of
Bis-benzylidene Acetal: Stereoselective Synthesis
of Anticancer Agent OGT2378 and Glycosidase
Inhibitor 1,4-Dideoxy-1,4-imino-L-xylitol
Appu Aravind, Muthukumar Gomathi Sankar,
Babu Varghese, and Sundarababu Baskaran*
FIGURE 1. Structures of NB-DNJ (1), NB-DGJ (2), and NP-DIJ (3).
Department of Chemistry, Indian Institute of Technology
Madras, Chennai 600036, India
owing to their ability to mimic their analogous pyranoses and
furanoses in interactions with carbohydrate-processing enzymes.
Thus, because of their biomimetic properties, iminosugars are
becoming important lead compounds for drug development in
a variety of therapeutic areas, including diabetes, viral infections,
and tumor metastasis.3,4
sbhaskar@iitm.ac.in
ReceiVed January 8, 2009
Butters and co-workers have shown that the hydrophobic
substituent on iminosugars increases the enzyme inhibitory
activities.5 N-Alkylated analogues of glucose and galactose
isomers have additional inhibitory activities toward ceramide
glucosyltransferase, an enzyme involved in the biosynthesis of
glycospingolipids (Figure 1).6,7
Recently, Ladisch et al. identified a new iminosugar, N-pentyl
deoxyidonojirimycin (NP-DIJ) (3), also known as OGT2378,
as a novel and potent anticancer agent that inhibits the synthesis
of gangliosides in cancer cells with no cytotoxic or antiprolif-
erative effects.8
Very recently, we reported a highly regioselective method
for the reductive cleavage of bis-benzylidene acetals of D-
mannitol using a BF3 ·Et2O/Et3SiH reagent system under mild
conditions, which resulted in the formation of highly function-
alized chiral intermediates in good yields (Scheme 1).9
A highly regioselective reductive cleavage of the bis-
benzylidene acetal of D-mannitol was performed using a
BF3 · Et2O/Et3SiH reagent system. A chiral intermediate 6
thus obtained was efficiently utilized in the stereoselective
synthesis of the anticancer agent OGT2378 (3) and glycosi-
dase inhibitor derivative N-tosyl 1,4-dideoxy-1,4-imino-L-
xylitol (22). Chemoselective reduction of azido epoxide 10
followed by regioselective intramolecular cyclization of
amino epoxide 11 resulted in the exclusive formation of
deoxyidonojirimycin derivative 12. By changing the order
of deprotection, the chiral intermediate 6 was readily
transformed to glycosidase inhibitor derivative 22.
(3) (a) Iminosugars as Glycosidase Inhibitors: Nojirimycin and Beyond; Stutz,
A. E., Ed.; Wiley-VCH: Weinheim, Germany, 1999. (b) Elbein, A. D. FASEB
J. 1991, 5, 3055. (c) Look, G. C.; Fotsch, C. H.; Wong, C.-H. Acc. Chem. Res.
1993, 26, 182. (d) Bols, M. Acc. Chem. Res. 1998, 31, 1. (e) Afarinkia, K.;
Bahar, A. Tetrahedron: Asymmetry 2005, 16, 1239. (f) Pearson, M. S. M.; Mathe´-
Allainmat, M.; Fargeas, V.; Lebreton, J. Eur. J. Org. Chem. 2005, 2159, and
references cited therein.
Generating a high level of skeletally and stereochemically
diverse intermediates from a common substrate is an especially
challenging and innovative task for synthetic organic chemists.
Meeting this formidable task is the goal of diversity-oriented
synthesis.1 Many strategies have been developed for the
diversity-oriented synthesis of biologically active and pharma-
ceutically important molecules.2 The polyhydroxylated pip-
eridines and pyrrolidines have been studied in the most detail,
(4) (a) Gruters, R. A.; Neefjes, J. J.; Tersmette, M.; de Goede, R. E. Y.;
Tulp, A.; Huisman, H. G.; Miedema, F.; Ploegh, H. L. Nature 1987, 330, 74.
(b) Bollen, M.; Stalmans, W. Eur. J. Biochem. 1989, 181, 775. (c) Tsuruoka,
T.; Fukuyasu, H.; Ishii, M.; Usui, T.; Shibahara, S.; Inouye, S. J. Antibiot. 1996,
49, 155. (d) Johnston, P. S.; Lebovitz, H. E.; Coniff, R. F.; Simonson, D. C.;
Raskin, P.; Munera, C. L. J. Clin. Endocrinol. Metab. 1998, 83, 1515. (e)
Nishimura, Y. Curr. Top. Med. Chem. 2003, 3, 575.
(5) (a) Butters, T. D.; van den Broek, L. A. G. M.; Fleet, G. W. J.; Krulle,
T. M.; Wormald, M. R.; Dwek, R. A.; Platt, F. M. Tetrahedron: Asymmetry
2000, 11, 113. (b) Butters, T. D.; Dwek, R. A.; Platt, F. M. Chem. ReV. 2000,
100, 4683. (c) Boucheron, C.; Desvergnes, V.; Compain, P.; Martin, O. R.; Lavi,
A.; Mackeen, M.; Wormald, M.; Dwek, R.; Butters, T. D. Tetrahedron:
Assymmetry 2005, 16, 1747.
(6) For biological activity, see: (a) ref 5. (b) Fan, J. Q.; Ishii, S.; Asano, N.;
Suzuki, Y. Nat. Med. 1999, 5, 112. (c) Watts, R. W. E. Philos. Trans. R. Soc.
London, Ser. B 2003, 358, 975. (d) Segraves, N. L.; Crews, P. J. Nat. Prod.
2005, 68, 118.
(7) For synthesis see: (a) Weber, K. T.; Hammache, D.; Fantini, J.; Ganem,
B. Bioorg. Med. Chem. Lett. 2000, 10, 1011. (b) Szczepina, M. G.; Johnston,
B. D.; Yuan, Y.; Svensson, B.; Pinto, B. M. J. Am. Chem. Soc. 2004, 126, 12458.
(8) (a) Weiss, M.; Hettmer, S.; Smith, P.; Ladisch, S. Cancer Res. 2003, 63,
3654. (b) For highlights, see: Borman, S. Chem. Eng. News 2005, (Sept 26), 39.
(9) (a) Aravind, A.; Baskaran, S. Tetrahedron Lett. 2005, 46, 743. (b) Aravind,
A.; Mohanty, S. K.; Pratap, T. V.; Baskaran, S. Tetrahedron Lett. 2005, 46,
2965.
(1) For reviews and seminal papers on diversity-oriented synthesis, see: (a)
Schreiber, S. L. Science 2000, 287, 1964. (b) Burke, M. D.; Berger, E. M.;
Schreiber, S. L. Science 2003, 302, 613. (c) Spring, D. R. Org. Biomol. Chem.
2003, 1, 3867. (d) Burke, M. D.; Schreiber, S. L. Angew. Chem., Int. Ed. 2004,
43, 46. (e) Arya, P.; Joseph, R.; Gan, Z.; Rakic, B. Chem. Biol. 2005, 12, 163.
(f) Wang, W.-W.; Ibrahem, I.; Co´rdova, A. Chem. Commun. 2006, 674.
(2) Please see ref 1. For diversity-oriented synthesis of iminosugars see: (a)
Lee, B. W.; Jeong, I.-Y.; Yang, M. S.; Choi, S. U.; Park, K. H. Synthesis 2000,
1305. (b) Pandey, G.; Kapur, M. Org. Lett. 2002, 4, 3883. (c) Takahata, H.;
Banba, Y.; Ouchi, H.; Nemoto, H. Org. Lett. 2003, 5, 2527. (d) Dhavale, D. D.;
Kumar, K. S. A.; Chaudhari, V. D.; Sharma, T.; Sabharwal, S. G.; Reddy, J. P.
Org. Biomol. Chem. 2005, 3, 3720. (e) Boucheron, C.; Compain, P.; Martin,
O. R. Tetrahedron Lett. 2006, 47, 3081.
2858 J. Org. Chem. 2009, 74, 2858–2861
10.1021/jo900030p CCC: $40.75 2009 American Chemical Society
Published on Web 03/11/2009

SCHEME 1. Regioselective Reductive Cleavage of
Bis-benzylidene Acetals of D-Mannitol
SCHEME 3. Synthesis of N-Boc Deoxyidonojirimycin
Derivative 13
SCHEME 4. Synthesis of Anticancer Agent OGT2378 (3)
SCHEME 2. Synthesis of Deoxyidonojirimycin Derivative
12
hydrogenation conditions furnished diol 7 in very good yield.
Exposure of diol derivative 7 to K2CO3 in MeOH resulted in a
smooth SN2 displacement of mesylate leading to an epoxide
with concomitant migration of the TBDPS group from the
secondary to the primary hydroxyl group.11 Interestingly, this
migration paved the way for the synthesis of deoxyidonojiri-
mycin with the desired stereochemistry (vide infra). Chemose-
lective conversion of epoxy alcohol 8 to epoxy azide 10 was
achieved under very mild conditions, by converting the hydroxyl
group to the corresponding triflate 9 and then treating it with
sodium azide at room temperature. Chemoselective reduction
of azide 10 in the presence of epoxide was readily achieved
under catalytic hydrogenation conditions using Lindlar’s cata-
lyst12 to yield amino epoxide 11, which on refluxing in methanol
underwent facile regioselective cyclization via 6-endo-tet mode13
to furnish deoxyidonojirimycin derivative 12 as the only product
in 93% yield.
The structure and the relative stereochemistry of the cyclized
product 12 was established by 2D NMR experiments and further
unambiguously confirmed by single crystal X-ray analysis on
the corresponding N-Boc deoxyidonojirimycin derivative 13
(Scheme 3 and Figure 2).
Reductive alkylation of deoxyidonojirimycin derivative 12,
with pentanal in combination with NaBH3CN, yielded
N-pentyl derivative 14, which was desilylated using TBAF
to give diol 15. Finally, the deprotection of the acetonide in
15 was readily achieved using DOWEX50WX8-100H+,
which resulted in the isolation of anticancer agent OGT2378
(3) in 90% yield (Scheme 4).
Herein we report our diversity-oriented approach for the
synthesis of the anticancer agent N-pentyl-deoxyidonojirimycin
(OGT2378) (3) and glycosidase inhibitor derivative N-tosyl 1,4-
dideoxy-1,4-imino-L-xylitol (22) from a common chiral inter-
mediate derived through the regioselective reductive cleavage
of the bis-benzylidene acetal of D-mannitol.
Our approach toward the stereo- and regioselective synthesis
of anticancer agent N-pentyl-deoxyidonojirimycin (OGT2378)
starting from the chiral intermediate 6 is shown in Schemes
2-4.10 Selective monoprotection of one of the hydroxy func-
tional groups of bis-benzylidene acetal 4 was achieved using
TBDPSCl in DMF, and the other hydroxy group was converted
to the corresponding mesylate 5 in good yield. Regioselective
reductive cleavage of bis-benzylidene acetal 5 with the BF3 ·Et2O
and Et3SiH reagent system resulted in the formation in 85%
yield of a diol, which was further converted to the corresponding
acetonide 6 using 2,2-DMP. Debenzylation of 6 under catalytic
1,4-Dideoxy-1,4-iminopentitols have been attracting the at-
tention of synthetic chemists as a result of their potential
(11) Mulzer, J.; Schollhorn, B. Angew. Chem., Int. Ed. 1990, 29, 431.
(12) (a) Reddy, P. G.; Pratap, T. V.; Kumar, G. D. K.; Mohanty, S. K.;
Baskaran, S. Eur. J. Org. Chem. 2002, 3740. (b) Corey, E. J.; Nicolaou, K. C.;
Balanson, R. D.; Machida, Y. Synthesis 1975, 590.
(13) (a) Kilonda, A.; Compernolle, F.; Peeters, K.; Joly, G. J.; Toppet, S.;
Hoornaert, G. J. Tetrahedron 2000, 56, 1005. (b) Somfai, P.; Marchand, P.;
Torsell, S.; Lindstro¨m, U. M. Tetrahedron 2003, 59, 1293. cis-Acetonide as well
as the corresponding cis- and trans-dibenzyl ether derivatives are known to give
a mixture of regioisomers. (c) Merrer, Y. L.; Poitout, L.; Depezay, J.-C.; Dosbaa,
I.; Geoffroy, S.; Foglietti, M.-J. Bioorg. Med. Chem. 1997, 5, 519. (d) Pino-
Gonza´lez, M. S.; Assiego, C.; Lo´pez-Herrera, F. J. Tetrahedron Lett. 2003, 44,
8353.
(10) The first and only synthesis of OGT2378 was reported in the patent
literature: Butters, T. D.; Dwek, R. A.; Fleet, G.; Orchard, M. G.; Platt, F. M.
PCT Int. Appl. WO 2002055498, 2002.
J. Org. Chem. Vol. 74, No. 7, 2009 2859

FIGURE 2. ORTEP diagram of N-Boc deoxyidonojirimycin deriva-
tive 13.
SCHEME 5. Stereoselective Synthesis of 1,4-Dideoxy-1,
4-imino-L-xylitol (23)
FIGURE 3. ORTEP diagram of N-tosyl derivative 22.
nished N-tosyl derivative 17 in good yield. Deprotection of silyl
ether with TBAF gave the corresponding hydroxy derivative
18, which was debenzylated under catalytic hydrogenation
conditions to yield the corresponding triol 19 in 95% yield.
Oxidative cleavage of the vicinal diol under heterogeneous
conditions using NaIO4 supported on silica gel yielded lactol
20, which upon refluxing in methanol with DOWEX50WX8-
100H+ furnished 2-methoxy-iminopentitol 21 in good yield.
2-Methoxy-iminopentitol derivative 21 upon treatment with
BF3 ·Et2O/Et3SiH yielded N-tosyl 1,4-dideoxy-1,4-imino-L-xy-
litol (22) in good yield.
The structure and relative stereochemistry of compound 22
was further confirmed by single crystal X-ray analysis (Figure
3). The conversion of N-tosyl 1,4-dideoxy-1,4-imino-L-xylitol
(22) to 1,4-dideoxy-1,4-imino-L-xylitol (23) in the presence of
NaNH2 in liquid ammonia has already been reported in the
literature.15h
In conclusion, the highly functionalized chiral intermediate
6 obtained through regioselective reductive cleavage of the bis-
benzylidene acetal of D-mannitol was efficiently utilized in the
stereoselective synthesis of the anticancer agent OGT2378 (3)
and glycosidase inhibitor derivative N-tosyl 1,4-dideoxy-1,4-
imino-L-xylitol (22) with overall yields of 12.6% and 16.5%,
respectively. Salient features of our synthesis are (i) facile
migration of the TBDPS group from the secondary to primary
hydroxyl group, which paved the way for the stereoselective
synthesis of deoxyidonojirimycin scaffold; (ii) chemoselective
reduction of azido epoxide 10 to amino epoxide 11 in the
presence of Lindlar’s catalyst; and (iii) highly regioselective
intramolecular cyclization of amino epoxide 11 to deoxyi-
donojirimycin scaffold (12), which was unambiguously estab-
lished by single crystal X-ray analysis. In addition, by changing
the order of deprotection and FGI, stereoselective synthesis of
glycosidase inhibitor derivative 22 was readily achieved from
the chiral intermediate 6. The success of our diversity-oriented
approach in the stereoselective synthesis of iminosugars under-
scores the power of the chiral intermediates derived through
the regioselective reductive cleavage of bis-benzylidene acetal
of D-mannitol.
biological activities.14 The versatility of our chiral intermediate
6 in the diversity-oriented synthesis of iminosugars is further
exemplified in the stereoselective synthesis of the glycosidase
inhibitor 1,4-dideoxy-1,4-imino-L-xylitol (23)15 by changing the
order of deprotection as well as functional group interconver-
sions (FGI) (Scheme 5). Thus, acetonide 6 on treatment with
NaN3 yielded azido derivative 16, which on catalytic hydroge-
nation with Lindlar’s catalyst and subsequent tosylation fur-
(14) (a) Asano, N.; Oseki, K.; Kizu, H.; Matsui, K. J. Med. Chem. 1994, 37,
3701. (b) Asano, N.; Kizu, H.; Oseki, K.; Tomioka, E.; Matsui, K.; Okamoto,
M.; Baba, M. J. Med. Chem. 1995, 38, 2349.
(15) (a) Hosaka, A.; Ichikawa, S.; Shindo, H.; Sato, T. Bull. Chem. Soc.
Jpn. 1989, 62, 797. (b) Buchanan, J. G.; Lumbard, K. W.; Sturgeon, R. J.;
Thompson, D. K.; Wightman, R. H. J. Chem. Soc., Perkin Trans. 1 1990, 699.
(c) Meng, Q.; Hesse, M. HelV. Chim. Acta 1991, 74, 445. (d) van der Klein,
P. A. M.; Filemon, W.; Broxterman, H. J. G.; vander Marel, G. A.; van Boom,
J. H. Synth. Commun. 1992, 22, 1763. (e) Huang, Y.; Dalton, D. R.; Carroll,
P. J. J. Org. Chem. 1997, 62, 372. (f) Kim, J. H.; Yang, M. S.; Lee, W. S.; Park,
K. H. J. Chem. Soc., Perkin Trans. 1 1998, 2877. (g) Wang, C.-C.; Luo, S.-Y.;
Shie, C.-R.; Hung, S.-C. Org. Lett. 2002, 4, 847. (h) Lei, A.; Liu, G.; Lu, X. J.
Org. Chem. 2002, 67, 974.
Experimental Section
(R)-2-(tert-Butyldiphenylsilyloxy)-1-((4R,5R)-2,2-dimethyl-5-
((S)-oxiran-2-yl)-1,3-dioxolan-4-yl)ethanol (8). To a stirred solu-
tion of compound 7 (400 mg, 0.74 mmol) in dry MeOH (10 mL)
was added K2CO3 (112 mg, 0.81 mmol), and the resultant mixture
was stirred at room temperature for 2 h. The reaction mixture was
concentrated under reduced pressure to remove MeOH. The residue
2860 J. Org. Chem. Vol. 74, No. 7, 2009

was diluted with water (10 mL) and extracted with EtOAc (2 × 10
mL). The combined organic layer was dried over anhydrous Na2SO4
and concentrated under reduced pressure. The crude compound was
purified by column chromatography over deactivated silica gel
(gradient elution with 20-30% EtOAc in hexane) to yield the pure
1.48-1.55 (m, 2H), 2.59-2.78 (m, 3H), 2.92 (dd, J ) 12.4, 4.8
Hz, 1H), 3.18-3.20 (m, 1H), 3.47 (t, J ) 8.8 Hz, 1H), 3.63 (dt, J
) 9.6, 4.4 Hz, 1H), 3.77 (dd, J ) 9.4, 5.6 Hz, 1H), 3.82-3.88 (m,
2H); 13C NMR (100 MHz, D2O) δ 15.9, 24.5, 28.3, 31.5, 53.8,
56.5, 58.1. 65.0, 71.7, 73.1, 76.4; HRMS (ESI) calcd for C11H24NO4
(M + H)+ 234.1705, found 234.1713.
title compound 8 (197 mg, 60%) as a viscous liquid. [R]30 -3.9
D
(c 1.0, CHCl3); IR (neat) 3520, 3072, 2944, 2832, 1462, 1427, 1376,
1260, 1216, 1174, 1110, 1062, 739, 704, 505 cm-1; 1H NMR (400
MHz, CDCl3) δ 1.08 (s, 9H), 1.32 (s, 3H), 1.37 (s, 3H), 2.77-2.82
(m, 2H), 2.99-3.14 (m, 1H), 3.65 (m, 1H), 3.79 (dd, J ) 10.2, 5.6
Hz, 1H), 3.84-3.91 (m, 2H), 3.96-3.99 (m, 1H), 7.37-7.45 (m,
6H), 7.65-7.67 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 19.2,
26.5, 26.8, 27.0, 44.8, 52.2, 65.1, 73.1, 77.1, 80.0, 109.9, 127.8,
127.8, 129.9, 129.9, 132.8, 132.9, 135.5, 135.5; HRMS(ESI) calcd
for C25H34O5SiNa (M + Na)+ 465.2073, found 465.2085.
(2S,3R,4R)-2-(Hydroxymethyl)-1-tosylpyrrolidine-3,4-diol (22).
To a stirred solution of compound 21 (70 mg, 0.22 mmol) in dry
CH2Cl2 (5 mL) was added Et3SiH (52 mg, 0.44 mmol) followed
by BF3 ·Et2O (157 mg, 1.1 mmol). The reaction mixture was stirred
for 4 h at room temperature. The reaction mass was then diluted
with CH2Cl2 (10 mL) and water (5 mL). The aqueous layer was
extracted with CH2Cl2 (2 × 10 mL). The combined organic layer
was dried over anhydrous Na2SO4 and concentrated under reduced
pressure to yield the crude compound. Column chromatographic
purification of the crude compound over silica gel using gradient
elution with 0-10% MeOH in EtOAc yielded the pure title
(3aR,4S,7S,7aR)-4-((tert-Butyldiphenylsilyloxy)methyl)-2,2-
dimethylhexahydro-[1,3]dioxolo[4,5-c]pyridin-7-ol (12). A solu-
tion of compound 11 (140 mg, 0.32 mmol) in MeOH was refluxed
for 4 h. The reaction mixture was then concentrated in vacuum,
and the residue was purified by column chromatography over silica
gel (gradient elution with 40-50% EtOAc in hexane) to yield
compound 22 (63 mg, 96%) as a colorless solid. [R]26 +19.3 (c
D
1.3, EtOH); IR (neat) 3339, 2926, 1328 cm-1; 1H NMR (400 MHz,
CD3COCD3) δ 2.44 (s, 3H), 3.21 (dd, J ) 11.2, 3.2 Hz, 1H), 3.60
(dd, J ) 10.8, 6.4 Hz, 1H), 3.65 (dd, J ) 11.0, 4.8 Hz, 1H),
3.89-3.96 (m, 2H), 4.00 (dd, J ) 11.0, 4.0 Hz, 1H), 4.09-4.10
(m, 1H), 7.42 (d, J ) 8.0 Hz, 2H), 7.76 (d, J ) 8.0 Hz, 2H); 13C
NMR (100 MHz, CD3COCD3) δ 21.3, 55.0, 61.8, 63.4, 74.4, 77.6,
128.6, 130.2, 144.1; HRMS (ESI) calcd for C12H17NO5SNa (M +
Na)+ 310.0725, found 310.0731.
deoxyidonojirimycin derivative 12 (130 mg, 93%) as a viscous
1
liquid. [R]26 -28.5 (c 1, CHCl3); IR (neat) 3472, 2928 cm-1; H
D
NMR (400 MHz, CDCl3) δ 1.06 (s, 9H), 1.29 (s, 3H), 1.39 (s,
3H), 2.40 (dd, J ) 12.0, 9.9 Hz, 1H), 2.94 (dd, J ) 12.1, 5.1 Hz,
1H), 3.37 (t, J ) 9.4 Hz, 1H), 3.52-3.55 (m, 1H), 3.60 (dd, J )
9.5, 5.4 Hz, 1H), 3.76-3.83 (m, 3H), 7.36-7.43 (m, 6H),
7.65-7.68 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 19.2, 26.5,
26.7, 26.8, 45.7, 56.0, 58.9, 70.7, 76.0, 79.5, 109.9, 127.7, 127.8,
129.7, 129.8, 133.2, 133.3, 135.5, 135.5; HRMS (ESI) calcd for
C25H36NO4Si (M + H)+ 442.2414, found 442.2419.
Acknowledgment. We thank CSIR and DST (New Delhi)
for financial support and DST-FIST (New Delhi) for NMR
facility. A.A. (SRF) thanks CSIR (New Delhi,) and M.G.S.
(SRF) thanks UGC (New Delhi) for fellowships.
2-(Hydroxymethyl)-1-pentylpiperidine-3,4,5-triol (3). To a
stirred solution of compound 15 (51 mg, 0.09 mmol) in dry MeOH
(3 mL) was added DOWEX50WX8-100H+ (51 mg), and the
resultant mixture was refluxed for 2 h. The reaction mixture was
treated with aqueous ammonia and filtered, and the filtrate was
concentrated under reduced pressure to yield pure OGT2378 (3)
Supporting Information Available: General experimental
1
procedures, experimental data, and H and 13C NMR spectra
for all new compounds and X-ray crystallographic data of 13
and 22 in CIF format. This material is available free of charge
via the Internet at http://pubs.acs.org.
(39 mg, 90%) as a viscous liquid. [R]27 +2.1 (c 1, CH3OH); IR
D
1
(neat) 3376, 2348, 2327, 1677, 1413, 1356, 1077 cm-1; H NMR
(400 MHz, D2O) δ 0.86 (t, J ) 6.4 Hz, 3H), 1.25-1.33 (m, 4H),
JO900030P
J. Org. Chem. Vol. 74, No. 7, 2009 2861