1498
G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 1493–1499
was dried over anhydrous Na2SO4 and concentrated in vacuo. The
residue was purified by column chromatography (EtOAc/hexane,
3H, CH3); 13C NMR (75 MHz, CDCl3) d 172.4, 95.3, 81.3, 78.6,
75.9, 72.9, 55.4, 40.5, 35.0, 33.6, 29.6, 28.0, 26.7, 21.6, 9.4, 5.0;
HRMS (ESI): [M+Na]+ m/z calcd for C18H36O6Na: 371.2409, found:
371.2415 (+1.4573 ppm error).
3:14) to afford 22 (2.07 g, 87%). ½a D25
¼ ꢀ10:2 (c 1.2, CHCl3),
ꢁ
Rf = 0.5 (EtOAc/hexane, 1:4); IR (neat): mmax 3469, 2937, 1735,
1459, 1372, 1255, 1038 cmꢀ1 1H NMR (300 MHz, CDCl3) d 4.2
;
(m, 2H, CH2–O–CH3), 3.84 (m, 1H, CH), 3.7 (s, 3H, O@C–OCH3),
3.45 (m, 1H, CH), 3.35 (s, 3H, CH2–O–CH3), 2.49 (dq, J = 3.0,
6.7 Hz, 1H, CH), 1.65–1.23 (m, 8H, 4 ꢃ CH2), 1.17 (d, J = 7.5 Hz,
3H, CH3), 0.90 (t, J = 7.5 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) d
176.4, 95.3, 78.5, 71.6, 55.4, 51.7, 44.3, 33.9, 33.5, 26.7, 21.6,
10.7, 9.4; HRMS (ESI): [M+Na]+ m/z calcd for C13H26O5Na:
285.1677, found: 285.1688 (+3.5279 ppm error).
4.1.19. (4R,5S,6S)-4-Hydroxy-6-[(4S)-4-hydroxyhexyl]-5-
methyltetrahydro-2H-2-pyranone 1
To a solution of ester 23 (0.43 g, 1.23 mmol) in 10 mL of THF
was added 1.8 mL of water. To the resulting solution 0.9 mL of con-
centrated HCl was added dropwise after which the mixture was
stirred at room temperature for 48 h. The reaction mixture was
quenched by adding NaHCO3 (1 g) then concentrated in vacuo,
and purified by silica gel column chromatography (EtOAc/hexanes,
1:1) to give 1 (0.214 g, 0.093 mmol, 75%) as light yellow liquid.
4.1.17. tert-Butyl (4R,5S,9S)-5-hydroxy-9-(methoxymethoxy)-4-
methyl-3-oxoundecanoate 2
½
a 2D5
ꢁ
¼ ꢀ39:5 (c 0.27, CHCl3), Rf = 0.3 (MeOH/CHCl3, 2:23); IR
To a solution of LDA, prepared from diisopropylamine (1.88 mL.
13.35 mmol) in anhydrous THF (20 mL) and n-butyllithium
(2.3 mL, 2.5 M in THF), tert-butyl acetate (1.32 g, 11.45 mmol) in
anhydrous THF (5 mL) was added at ꢀ78 °C. Then, the hydroxyes-
ter 22 (1 g, 3.81 mmol) in anhydrous THF (5 mL) was added drop-
wise at ꢀ78 °C. The mixture was stirred at ꢀ50 °C for 1.5 h, and,
then, at ꢀ15 °C for 15 min. Ice-water (20 mL) was added to quench
the reaction, and the aqueous layer was extracted with ether
(2 ꢃ 25 mL). The combined organic layer was washed with satu-
rated NaHC03 (20 mL) and water (2 ꢃ 15 mL), and dried over anhy-
drous Na2SO4. The solvent was removed under reduced pressure,
and the residue was purified by column chromatography (EtOAc/
(neat): mmax 3445, 2929, 1712, 1459, 1382, 1253 cmꢀ1 1H NMR
;
(400 MHz, CDCl3) d 4.71 (ddd, J = 2.5, 4.7, 8.1 Hz, 1H, CH), 4.06
(ddd, J = 3.2, 3.4, 5.6 Hz, 1H, CH), 3.55 (m, 1H, CH), 2.81 (dd,
J = 5.5, 18.5 Hz, 1H, O@CCHaHb), 2.53 (ddd, J = 0.9, 3.2, 18.1 Hz,
1H, O@CCHaHb), 1.95 (m, 1H, CH), 1.74 (m, 1H, CHaHb), 1.65 (m,
2H, CH2), 1.50 (m, 3H, CHaHb and CH2), 1.42 (m, 2H, CH2), 0.95
(d, J = 7.2 Hz, 3H, CH3), 0.94 (t, J = 7.3 Hz, 3H, CH3); 13C NMR
(75 MHz, CDCl3) d 170.3, 78.0, 73.0, 68.6, 37.4, 36.4, 35.8, 31.7,
30.3, 21.6, 10.2, 9.8; HRMS (ESI): [M+Na]+ m/z calcd for
C12H22O4Na: 253.1415, found: 253.1425 (+3.6377 ppm error).
Acknowledgment
hexane, 4:21) to afford 2 (1.08 g, 82%). ½a D25
¼ ꢀ5:0 (c 1.1, CHCl3),
ꢁ
Rf = 0.5 (EtOAc/hexane, 1:4); IR (neat): mmax 3451, 2933, 1735,
P.G. thanks CSIR, New Delhi, for the award of Fellowship.
1708, 1639, 1459, 1369, 1317, 1253, 1149, 1037 cmꢀ1 1H NMR
;
(300 MHz, CDCl3) d 4.60 (m, 2H, CH2–OCH3), 3.93 (m, 1H, CH),
3.50–3.37 (m, 3H, O@C–CH2–C@O, CH), 3.35 (s, 3H, CH2–O–CH3),
2.68 (dq, J = 3.0, 7.5 Hz, 1H, CH), 1.58–1.41 (m, 8H, 4 ꢃ CH2), 1.47
(s, 9H, tBu), 1.14 (d, J = 7.5 Hz, 3H, CH3), 0.90 (t, J = 7.5 Hz, 3H,
CH3); 13C NMR (75 MHz, CDCl3) d 207.8, 166.5, 95.3, 82.1, 78.5,
70.8, 55.4, 50.9, 49.5, 34.0, 33.5, 27.9, 26.7, 21.6, 9.5, 9.4; HRMS
(ESI): [M+Na]+ m/z calcd for C18H34O6Na: 369.2253, found:
369.2259 (+1.6009 ppm error).
References
1. Crouse, G. D.; Sparks, T. C. Rev. Toxicol. 1998, 2, 133–146.
2. Martin, C. J.; Timoney, M. C.; Sheridan, R. M.; Kendrew, S. G.; Wilkinson, B.;
Staunton, J.; Leadlay, P. F. Org. Biomol. Chem. 2003, 1, 4144–4147.
3. O’Hagen, D. In The Polyketides Metabolites; O’Hagen, D., Ed.; Ellis Horwood: New
York, 1991; pp 116–137.
4. Chakraborty, T. K.; Goswami, R. K. Tetrahedron Lett. 2004, 45, 7637–7639.
5. Yadav, J. S.; Reddy, P. M. K.; Reddy, P. V. Tetrahedron Lett. 2007, 48, 1037–1039.
6. (a) Sabitha, G.; Sudhakar, K.; Reddy, N. M.; Rajkumar, M.; Yadav, J. S.
Tetrahedron Lett. 2005, 46, 6567–6570; (b) Sabitha, G.; Narjis, F.; Swapna, R.;
Yadav, J. S. Synthesis 2006, 17, 2879–2884; (c) Sabitha, G.; Reddy, E. V.; Yadagiri,
K.; Yadav, J. S. Synthesis 2006, 19, 3270–3274; (d) Sabitha, G.; Sudhakar, K.;
Yadav, J. S. Tetrahedron Lett. 2006, 47, 8599–8602; (e) Sabitha, G.; Bhaskar, V.;
Yadav, J. S. Tetrahedron Lett. 2006, 47, 8179–8181; (f) Sabitha, G.; Swapna, R.;
Reddy, E. V.; Yadav, J. S. Synthesis 2006, 24, 4242–4246; (g) Sabitha, G.;
Bhikshapathi, M.; Yadav, J. S. Synth. Commun. 2007, 37, 561–569; (h) Sabitha,
G.; Gopal, P.; Yadav, J. S. Synth. Commun. 2007, 37, 1495–1502; (i) Sabitha, G.;
Yadagiri, K.; Yadav, J. S. Tetrahedron Lett. 2007, 48, 1651–1652; (j) Sabitha, G.;
Yadagiri, K.; Yadav, J. S. Tetrahedron Lett. 2007, 48, 8065–8068; (k) Sabitha, G.;
Bhaskar, V.; Yadav, J. S. Synth. Commun. 2008, 38, 1–12; (l) Sabitha, G.; Bhaskar,
V.; Siva Sankara Reddy, S.; Yadav, J. S. Tetrahedron 2008, 64, 10207–10213.
7. Sabitha, G.; Fatima, N.; Swapna, R.; Yadav, J. S. Synthesis 2006, 2879–2884.
8. Sabitha, G.; Fatima, N.; Gopal, P.; Reddy, C. N.; Yadav, J. S. Tetrahedron:
Asymmetry 2009, 20, 184–191.
4.1.18. tert-Butyl (3R,4R,5S,9S)-3,5-dihydroxy-9-
(methoxymethoxy)-4-methylundecanoate 23
A solution of diethylmethoxyborane (2.6 mL, 1 M in THF) and 2
(0.75 g, 2.16 mmol) in anhydrous THF–MeOH (20 mL; 4:1) was
stirred for 2 h at room temperature under nitrogen. Then, the solu-
tion was cooled to ꢀ78 °C and solid NaBH4 (98.8 mg, 2.6 mmol)
was added in one portion. The mixture was stirred for 6 h at
ꢀ78 °C, and a mixture of 30% H2O2 (10 mL), phosphate buffer (pH
7, 20 mL), and methanol (20 mL) was added. Almost all of the or-
ganic solvent was removed under reduced pressure, and the resid-
ual aqueous solution was extracted with CH2C12 (2 ꢃ 50 mL). The
extract was dried over anhydrous Na2SO4 and concentrated. To
the residue was added glacial AcOH (1 mL) in EtOAc (20 mL) and
stirred for 2 h to completely decompose the boric acid ester of
diols. Then the reaction was quenched by saturated NaHCO3
(5 mL). The organic layer was separated, the aqueous layer was
again extracted with EtOAc (2 ꢃ 30 mL) and dried over anhydrous
Na2SO4, the solvent was removed under reduced pressure, the res-
idue was purified by silica gel column chromatography (EtOAc/
EtMgBr, THF
OBn
HO
16
(HCHO)n
OBn
16a
(-)-DET, Ti(OiPr)4
TBHP, -24 ºC
LAH, dry THF
r.t., 6 h.
HO
OBn
16b
TPP, I2
hexane, 1:5) to afford 23 (0.588 g, 1.68 mmol, 78%). ½a D25
ꢁ
¼ þ3:0
O
O
( )3
HO
( )3
OBn
I
OBn
imidazole,
(c 1.0, CHCl3), Rf = 0.3 (EtOAc/hexane, 1:4); IR (neat): mmax 3447,
7
24
Et2O/CH3CN (3:1)
0 ºC-rt, 20 min
2933, 1726, 1636, 1460, 1369, 1154, 1037, 760 cmꢀ1 1H NMR
;
(300 MHz, CDCl3) d 4.6 (m, 2H, CH2–OCH3), 4.20 (dt, J = 2.2,
9.8 Hz, 1H, CH), 3.85(m, 1H, CH), 3.45 (m, 1H, CH), 3.35 (s, 3H,
CH2–O–CH3), 2.50 (dd, J = 6.0, 15.8 Hz, 1H O@C–CHaHb), 2.25 (dd,
J = 3.0, 16.6 Hz, 1H, O@C–CHaHb), 1.57–1.27 (m, 9H, 4 ꢃ CH2, CH),
1.46 (s, 9H, tBu), 0.91 (d, J = 6.0 Hz, 3H, CH3), 0.90 (t, J = 6.7 Hz,
Zn dust,
EtOH, reflux
OH
( )3
30 min
OBn
17