R.K. Rej et al. / Tetrahedron 70 (2014) 2634e2642
2641
4.41e4.32 (m, 2H), 4.18e4.11 (m, 1H), 3.97e3.94 (m, 1H),
3.67e3.62 (m, 1H), 3.34 (s, 3H), 2.44e2.36 (m, 2H), 1.78e1.70 (m,
2H), 1.35e1.30 (m, 9H), 1.29e1.21 (m, 9H), 1.20e1.00 (m, 9H),
(m, 2H), 1.55 (s, 3H), 1.38 (s, 3H), 1.34e1.21 (m, 10H), 0.88e0.84 (m,
3H). 13C NMR (50 MHz, CDCl3)
: 175.0,128.1,126.6,109.3, 78.5, 75.7,
70.1, 33.6, 31.9, 31.8, 31.2, 29.4, 29.2, 28.4, 26.2, 24.5, 22.6, 14.0.
HRMS (ESI) for C19H32O5Na [MþNa]þ, calculated: 363.2145; found:
363.2148.
d
0.93e0.86 (m, 3H). 13C NMR (50 MHz, CDCl3)
d: 178.2, 136.4,
134.7, 133.5, 129.9, 129.5, 129.3, 127.4, 127.1, 108.6, 94.0, 81.0, 78.0,
74.7, 72.3, 55.8, 33.4, 31.9, 30.3, 29.9, 29.3, 28.2, 27.4, 25.5, 25.0,
22.8, 19.8, 14.3. HRMS (ESI) for C37H56O7SiNa [MþNa]þ, calcu-
lated: 663.3692; found: 663.3677.
4.2.8. 4-((3aR,4R,9S,11aS,E)-4-Heptyl-2,2-dimethyl-6-oxo-
4,6,7,8,9,11a-hexahydro-3aH-[1,3]dioxolo[4,5-c]oxecin-9-yloxy)-4-
oxobutanoic acid (20). Succinic anhydride (22 mg, 0.22 mmol) was
taken in dry DCM (2 ml). DCC (61 mg, 0.3 mmol), DMAP (5 mg), and
alcohol 19 (50 mg, 0.15 mmol) were sequentially added to the re-
action mixture. The reaction mixture was kept at room temperature
for 24 h. DCM was evaporated and the crude ester was purified by
flash chromatography (EtOAc:hexane¼1:10) to afford the ester 20
(60 mg) in 90% yield.
4.2.5. (S,E)-6-((4S,5R)-5-((R)-1-Hydroxyoctyl)-2,2-dimethyl-1,3-
dioxolan-4-yl)-4-(methoxymethoxy)hex-5-enoic
acid
(17). Compound 16 (128 mg, 0.2 mmol) was taken in dry THF
(2 ml). TBAF (1 M in THF, 0.4 ml, 0.4 mmol) was added to the so-
lution, and the reaction mixture was then stirred for 3 h at 40 ꢁC.
THF was then evaporated, and water (2 ml) was added to it, the
reaction mixture was extracted with EtOAc (50 ml), the organic
layer was washed with NaHCO3 and brine, and dried (Na2SO4). It
was purified by flash chromatography (EtOAc:hexane¼1:1) to af-
ford compound 17 (70 mg) in 88% yield.
Rf¼0.4 (EtOAc:hexane¼1:10). [
a
]
d
28 þ31.2 (c 0.5, CHCl3). 1H NMR
D
of compound 20 (400 MHz, CDCl3)
: 5.91 (dd, J¼3.2, 15.2 Hz, 1H),
5.63 (dd, J¼2.4, 8.8 Hz, 1H), 5.29e5.18 (m, 1H), 4.96e4.88 (m, 1H),
4.72e4.67 (m, 1H), 3.98 (dd, J¼4.4, 9.6 Hz, 1H), 2.77e2.55 (m, 4H),
2.40e2.28 (m, 2H), 2.19e1.99 (m, 4H), 1.54 (s, 3H), 1.36 (s, 3H),
Rf¼0.1 (EtOAc:hexane¼1:2). [
a
]
28 þ9.9 (c 0.2, CHCl3). 1H NMR of
D
compound 17 (200 MHz, CDCl3)
d
: 5.43e5.33 (m, 2H), 4.50e4.45
1.34e1.18 (m, 10H), 0.88e0.84 (m, 3H). 13C NMR (50 MHz, CDCl3)
d:
(m, 1H), 4.43e4.29 (m, 2H), 4.12e4.09 (m, 1H), 3.95e3.92 (m, 1H),
3.64e3.56 (m, 1H), 3.27 (s, 3H), 2.38e2.34 (m, 2H), 1.73e1.70 (m,
2H), 1.38e1.26 (m, 9H), 1.25e1.15 (m, 9H), 0.87e0.84 (m, 3H). 13C
177.3, 174.1, 171.3, 128.2, 123.7, 109.4, 78.5, 76.9, 75.5, 71.0, 31.9, 31.7,
30.9, 30.5, 29.3, 29.1, 28.9, 28.5, 28.4, 26.1, 24.4, 22.6, 14.0. HRMS
(ESI) for
463.2284.
C
23H36O8Na [MþNa]þ, calculated: 463.2290; found:
NMR (50 MHz, CDCl3) d: 178.2, 108.6, 94.0, 81.0, 78.0, 74.8, 72.3,
55.8, 33.5, 31.9, 30.3, 29.9, 29.3, 28.2, 27.5, 25.5, 25.0, 22.8,19.8, 14.3.
HRMS (ESI) for C21H38O7Na [MþNa]þ, calculated: 425.2515; found:
425.2518.
4.2.9. 4-((5S,8S,9S,10R,E)-10-Heptyl-8,9-dihydroxy-2-oxo-
3,4,5,8,9,10-hexahydro-2H-oxecin-5-yloxy)-4-oxobutanoic acid (xyo-
lide). To a solution of compound 20 (26 mg, 0.06 mmol) in THF
(5 ml), HCl (1 ml, 2 M) was added at room temperature and stirred
for 12 h. Water was added to the reaction mixture and it was
extracted with ethyl acetate. The organic layer was washed with
NaHCO3 and brine. It was then dried over MgSO4, concentrated in
a rotary evaporator, and purified by silica gel column chromatog-
raphy (EtOAc:hexane¼1:1) to afford the target molecule xyolide
4.2.6. (3aR,4R,9S,11aS,E)-4-Heptyl-9-(methoxymethoxy)-2,2-
dimethyl-7,8,9,11a-tetrahydro-3aH-[1,3]dioxolo[4,5-c]oxecin-6(4H)-
one (18). To a solution of MBNA (46 mg, 0.13 mmol), DIPEA
(0.181 ml, 1.05 mmol), and DMAP (15 mg, 0.12 mmol) in toluene
(35 ml) at room temperature was added a solution of seco-acid 17
(41 mg, 0.1 mmol) in toluene (15 ml). After that the reaction mix-
ture was stirred for 24 h at 60 ꢁC, then cooled to room temperature
and quenched by adding saturated aqueous NaHCO3 solution. The
organic solution was then successively washed with water, brine,
and dried over MgSO4. The organic solvent was evaporated to fur-
nish the crude product, which was purified by silica gel column
chromatography (EtOAc:hexane¼1:20) to afford the lactone 18
(26 mg) in 68% yield.
(21 mg) in 85% yield.
28
Rf¼0.3 (EtOAc:hexane¼2:1). [
a
]
D
þ10.1 (c 0.8, CHCl3). 1H NMR
of Xyolide (400 MHz, CDCl3)
d
: 5.86 (dd, J¼1.8, 15.4 Hz, 1H), 5.50
(ddd, J¼1.4, 9.6, 15.4 Hz, 1H), 5.18e5.10 (m, 1H), 4.99 (td, J¼1.8,
9.6 Hz, 1H), 4.52e4.49 (m, 1H), 3.60 (dd, J¼1.8, 9.6 Hz, 1H), 2.67 (t,
J¼6.2 Hz, 2H), 2.62 (t, J¼5.8 Hz, 2H), 2.40e2.31 (m, 1H), 2.12e1.98
(m, 3H), 1.91e1.82 (m, 1H), 1.57e1.48 (m, 1H), 1.37e1.17 (m, 10H),
Rf¼0.3 (EtOAc:hexane¼1:10). [
a
]
d
28 þ11.9 (c 0.3, CHCl3). 1H NMR
0.88 (t, J¼6.8 Hz, 3H). 13C NMR (50 MHz, CDCl3)
d: 176.5,174.5,171.6,
D
of compound 18 (200 MHz, CDCl3)
: 5.84 (dd, J¼3.8, 15.4 Hz, 1H),
132.6, 123.5, 76.4, 73.5, 72.5, 70.8, 31.7, 31.5, 31.2, 29.6, 29.4, 29.3,
29.1, 28.8, 24.5, 22.6, 14.0. HRMS (ESI) for C20H32O8Na [MþNa]þ,
calculated: 423.1982; found: 423.1978.
5.38e5.24 (m, 2H), 4.75 (d, J¼6.6 Hz, 1H), 4.56 (d, J¼6.6 Hz, 1H),
4.43e4.36 (m, 1H), 4.17e4.08 (m, 2H), 3.38 (s, 3H), 2.45e2.23 (m,
4H), 1.71e1.60 (m, 2H), 1.44 (s, 3H), 1.38 (s, 3H), 1.32e1.10 (m, 10H),
0.90e0.87 (m, 3H). 13C NMR (50 MHz, CDCl3)
d: 175.0, 133.9, 130.0,
Acknowledgements
108.2, 94.2, 79.0, 78.2, 77.8, 68.9, 55.6, 32.9, 31.9, 31.4, 29.9, 29.4,
29.3, 28.9, 26.1, 25.5, 22.8, 14.2. HRMS (ESI) for C21H36O6Na
[MþNa]þ, calculated: 407.2409; found: 407.2412.
Financial support from CSIR-India is gratefully acknowledged
(Grant: 02(0020)/11/EMR-II). We are also thankful to DST-India
(IRPHA) for NMR instrument. One of the authors R.K.R. is thank-
ful to CSIR-India for providing research fellowship.
4.2.7. (3aR,4R,9S,11aS,E)-4-Heptyl-9-hydroxy-2,2-dimethyl-
7,8,9,11a-tetrahydro-3aH-[1,3]dioxolo[4,5-c]oxecin-6(4H)-one
(19). To a solution of compound 18 (69 mg, 0.18 mmol) in dry DCM
(10 ml) was added activated KHSO4$SiO2 (0.68 g, 4.3 mmol). The
reaction mixture was stirred for 4 h at room temperature then fil-
tered through a plug of cotton wool and washed with ethyl acetate
until the filtrate dripped clear. The filtrate was concentrated in
vacuo to give a black residue. Purification of the residue by flash
column chromatography using (EtOAc:hexane¼1:10) afforded al-
Supplementary data
Copies of 1H, 13C NMR spectra of all compounds, and HPLC
chromatogram of racemic and enantiopure 3 and 7 is provided.
Supplementary data related to this article can be found at http://
cohol 19 (52 mg, 86%) as a yellow oil.
28
Rf¼0.4 (EtOAc:hexane¼1:5). [
a
]
þ39.9 (c 0.2, CHCl3). 1H NMR
D
d
References and notes
of compound 19 (200 MHz, CDCl3)
: 5.82 (dd, J¼3.2, 15.8 Hz, 1H),
5.66 (dd, J¼1.6, 8.4 Hz, 1H), 4.96e4.90 (m, 1H), 4.70e4.67 (m, 1H),
4.21e3.98 (m, 2H), 2.37e2.31 (m, 2H), 2.09e2.01 (m, 2H), 1.85e1.74