R. K. Rej, S. Nanda
FULL PAPER
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 5.60 (td, J = 12.0, (qd, J = 9.6, 6.2 Hz, 1 H), 2.07–1.93 (m, 3 H), 1.61–1.57 (m, 2 H),
4.0 Hz, 1 H), 5.44 (td, J = 10.4, 2.0 Hz, 1 H), 5.03 (dd, J = 10.0, 1.31–1.25 (m, 10 H), 0.88 (t, J = 6.8 Hz, 3 H) ppm. 13C NMR
5.6 Hz, 1 H), 4.89 (dt, J = 10.8, 2.4 Hz, 1 H), 4.68 (dd, J = 6.4, (50 MHz, CDCl3): δ = 174.1, 134.5, 126.8, 77.8, 74.1, 66.4, 45.4,
2.0 Hz, 2 H), 4.61 (dd, J = 10.4, 6.8 Hz, 2 H), 3.67 (dt, J = 11.6, 31.4, 31.3, 31.0, 29.6, 25.3, 25.1, 22.3, 14.0, 7.9 ppm. HRMS (ESI):
3.6 Hz, 1 H), 3.41 (s, 3 H), 3.37 (s, 3 H), 3.06–2.99 (m, 1 H), 2.69
(qd, J = 13.2, 3.6 Hz, 1 H), 2.00–1.89 (m, 1 H), 1.87–1.77 (m, 1
H), 1.70–1.56 (m, 3 H), 1.52–1.47 (m, 1 H), 1.36–1.27 (m, 6 H),
1.20–1.18 (m, 3 H), 0.92 (t, J = 6.6 Hz, 3 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 172.7, 134.1, 126.8, 96.2, 94.5, 75.9, 72.8,
70.4, 55.8, 55.7, 43.0, 31.8, 29.1, 26.7, 26.0, 24.3, 22.7, 14.2,
8.5 ppm. HRMS (ESI): calcd. for C19H34O6NaSi [M + Na]+
381.2253; found 381.2254.
calcd. for C15H26O4Na [M + Na]+ 293.1728; found 293.1729.
(Z,3S,4R,9S,10R)-3,4,7,8,9,10-Hexahydro-4,9-dihydroxy-3-methyl-
10-pentyloxecin-2-one (49): [α]2D8 = +26.5 (c = 1.1, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 5.75 (ddd, J = 11.1, 4.5, 1.1 Hz, 1
H), 5.37 (dt, J = 9.9, 2.2 Hz, 1 H), 5.11–5.09 (m, 1 H), 4.62 (t, J =
9.9 Hz, 1 H), 3.82–3.80 (m, 1 H), 2.77–2.68 (m, 1 H), 2.55–2.49 (m,
1 H), 2.13–1.90 (m, 2 H), 1.67–1.49 (m, 2 H), 1.42–1.20 (m, 10 H),
0.88 (m, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 174.6, 133.8,
130.0, 77.6, 74.3, 69.5, 49.1, 31.3, 30.8, 29.7, 25.3, 25.1, 22.4, 14.8,
13.8 ppm. HRMS (ESI): calcd. for C15H26O4Na [M + Na]+
293.1728; found 293.1729.
(Z,3S,4R,9R,10R)-3,4,7,8,9,10-Hexahydro-4,9-bis(methoxymeth-
oxy)-3-methyl-10-pentyloxecin-2-one (45): [α]2D8 = +26.1 (c = 1.1,
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 5.59 (td, J = 11.6,
3.6 Hz, 1 H), 5.28 (td, J = 11.2, 2.0 Hz, 1 H), 4.83 (dt, J = 8.4,
2.8 Hz, 1 H), 4.67 (dd, J = 11.6, 6.4 Hz, 2 H), 4.60 (d, J = 6.8 Hz,
1 H), 4.49 (d, J = 6.8 Hz, 1 H), 4.49–4.44 (m, 1 H), 3.69 (dt, J =
12.0, 3.6 Hz, 1 H), 3.43 (s, 3 H), 3.37 (s, 3 H), 2.64 (qd, J = 6.8,
3.6 Hz, 1 H), 2.51–2.47 (m, 1 H), 2.04–1.88 (m, 1 H), 1.76–1.72 (m,
1 H), 1.69–1.62 (m, 1 H), 1.61–1.58 (m, 1 H), 1.42–1.22 (m, 10 H),
0.82 (t, J = 6.5 Hz, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ =
172.8, 134.2, 130.0, 96.1, 94.1, 75.3, 73.1, 72.6, 55.8, 55.6, 46.8,
31.7, 29.1, 26.5, 25.8, 24.2, 22.7, 14.9, 14.1 ppm. HRMS (ESI):
calcd. for C19H34O6NaSi [M + Na]+ 381.2253; found 381.2254.
(Z,3R,4S,9S,10R)-3,4,7,8,9,10-Hexahydro-4,9-dihydroxy-3-methyl-
10-pentyloxecin-2-one (50): [α]2D8 = –31.0 (c = 0.2, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 5.69 (ddd, J = 10.9, 5.6, 1.4 Hz, 1 H), 5.47–
5.30 (m, 2 H), 5.12 (t, J = 9.2 Hz, 1 H), 4.67–4.57 (dt, J = 9.6,
3.4 Hz, 1 H), 2.55–2.40 (m, 2 H), 2.15–1.96 (m, 2 H), 1.89–1.70 (m,
2 H), 1.41–1.29 (m, 10 H), 0.87 (t, J = 6.7 Hz, 3 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 174.8, 133.9, 130.2, 77.9, 74.5, 69.7, 49.4,
31.7, 31.6, 31.2, 25.5, 25.4, 22.6, 15.0, 14.1 ppm. HRMS (ESI):
calcd. for C15H26O4Na [M + Na]+ 293.1728; found 293.1729.
(Z,3R,4R,9S,10R)-3,4,7,8,9,10-Hexahydro-4,9-dihydroxy-3-meth-
yl-10-pentyloxecin-2-one (51): [α]2D8 = –89.5 (c = 0.8, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 5.78 (ddd, J = 11.6, 5.2, 1.2 Hz, 1
H), 5.50–5.40 (m, 1 H), 5.28 (dt, J = 9.3, 3.6 Hz, 1 H), 5.17–5.14
(m, 1 H), 3.84–3.78 (m, 1 H); 3.09–3.00 (m, 1 H); 2.79–2.65 (m, 1
H), 2.06–1.93 (m, 2 H), 1.82–1.63 (m, 2 H), 1.41–1.17 (m, 10 H),
0.87 (t, J = 6.8 Hz, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ =
174.3, 134.8, 127.1, 78.1, 74.4, 66.7, 45.7, 31.7, 31.6, 31.3, 29.9,
25.6, 22.7, 14.2, 8.2 ppm. HRMS (ESI): calcd. for C15H26O4Na [M
+ Na]+ 293.1728; found 293.1729.
(Z,3R,4S,9R,10R)-3,4,7,8,9,10-Hexahydro-4,9-bis(methoxymeth-
oxy)-3-methyl-10-pentyloxecin-2-one (46): [α]2D8 = –10.1 (c = 1.1,
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 5.59 (td, J = 11.2,
3.2 Hz, 1 H), 5.31 (t, J = 9.6 Hz, 1 H), 4.82 (dt, J = 8.0, 1.8 Hz, 1
H), 4.69–4.59 (m, 4 H), 4.50–4.44 (m, 1 H), 3.72 (dt, J = 7.2,
3.6 Hz, 1 H), 3.39 (s, 3 H), 3.36 (s, 3 H), 2.67–2.59 (m, 1 H), 2.51–
2.47 (m, 1 H), 2.04–2.00 (m, 1 H), 1.71–1.69 (m, 1 H), 1.60–1.34
(m, 2 H), 1.31–1.27 (m, 10 H), 0.89 (t, J = 6.8 Hz, 3 H) ppm. 13C
NMR (50 MHz, CDCl3): δ = 172.5, 133.9, 129.7, 95.9, 93.9, 75.1,
72.9, 72.4, 55.6, 55.4, 46.5, 31.4, 29.5, 28.9, 26.3, 25.6, 24.0, 22.4,
14.8, 13.8 ppm. HRMS (ESI): calcd. for C19H34O6NaSi [M +
Na]+ 381.2253; found 381.2254.
(Z,3S,4S,9R,10R)-3,4,7,8,9,10-Hexahydro-4,9-dihydroxy-3-methyl-
10-pentyloxecin-2-one (52): [α]2D8 = +7.2 (c = 0.5, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 5.51–5.45 (overlapped, 2 H), 5.19 (dd, J =
8.0, 6.0 Hz, 1 H), 4.78 (dd, J = 8.4, 2.4 Hz, 1 H), 3.82 (dt, J = 11.6,
3.6 Hz, 1 H), 3.01 (t, J = 6.4 Hz, 1 H), 2.72–2.63 (m, 1 H), 2.13–
1.90 (m, 2 H), 1.67–1.49 (m, 2 H), 1.45–1.20 (m, 10 H), 0.88 (t, J
= 6.8 Hz, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 173.0, 132.8,
128.3, 77.7, 66.9, 66.6, 44.2, 31.8, 30.7, 26.2, 26.0, 24.4, 22.7, 14.2,
7.7 ppm. HRMS (ESI): calcd. for C15H26O4Na [M + Na]+
293.1728; found 293.1729.
(3R,4R,9R,10R,Z)-4,9-bis(methoxymethoxy)-3-methyl-10-pentyl-
3,4,7,8,9,10-hexahydro-2H-oxecin-2-one (47): Inseparable mixture.
1H NMR (200 MHz, CDCl3): δ = 5.59–5.01 (m, 2 H), 4.99–4.91
(m, 2 H), 4.86–4.57 (m, 3 H), 4.19–4.14 (m, 1 H), 3.65–3.61 (m, 1
H), 3.41–3.37 (m, 6 H), 3.06–2.99 (m, 1 H), 2.70–2.62 (m, 1 H),
2.13–2.10 (m, 2 H), 1.90–1.60 (m, 3 H), 1.30–1.09 (m, 9 H), 0.91–
0.87 (m, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 174.7, 172.6,
138.2, 135.4, 134.0, 126.7, 120.5, 115.1, 96.8, 96.1, 94.4, 93.9, 79.3,
75.9, 74.4, 72.7, 70.3, 56.0, 55.8, 55.7, 55.6, 44.7, 42.9, 31.9, 31.7,
29.7, 29.1, 26.7, 26.0, 25.4, 24.2, 22.7, 14.1, 8.47 ppm. HRMS
(ESI): calcd. for C19H34O6NaSi [M + Na]+ 381.2253; found
381.2254.
(Z,3S,4R,9R,10R)-3,4,7,8,9,10-Hexahydro-4,9-dihydroxy-3-meth-
yl-10-pentyloxecin-2-one (53): [α]2D8 = +19.0 (c = 1.1, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 5.51–5.38 (overlapped, 2 H), 4.75
(dt, J = 10.8, 2.4 Hz, 1 H), 4.52 (t, J = 9.2 Hz, 1 H), 3.88 (dt, J =
11.6, 3.6 Hz, 1 H), 2.62 (dq, J = 13.6, 4.0 Hz, 1 H), 2.43 (qd, J =
9.6, 6.9 Hz, 1 H), 2.13–2.10 (m, 1 H), 1.66–1.44 (m, 3 H), 1.45–
1.27 (m, 10 H), 0.90 (t, J = 6.8 Hz, 3 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 173.4, 131.9, 131.7, 77.2, 69.8, 66.7, 48.5, 31.7, 30.9,
26.1, 25.9, 24.3, 22.7, 14.8, 14.1 ppm. HRMS (ESI): calcd. for
C15H26O4Na [M + Na]+ 293.1728; found 293.1729.
MOM Deprotection: To a solution of ring-closed compound
(40 mg, 0.15 mmol) in MeOH was added HCl (2M, 0.08mL,
0.16 mmol) at room temp. and the mixture was stirred for 10 h.
Water was added and the reaction mixture was extracted with ethyl
acetate. The organic layer was washed with NaHCO3 and brine,
then dried with MgSO4, concentrated in a rotary evaporator and
purified by silica gel column chromatography (EtOAc/hexane, 1:3)
to afford the target molecule cytospolide (ca 34 mg, ca. 88%).
(Z,3R,4S,9R,10R)-3,4,7,8,9,10-Hexahydro-4,9-dihydroxy-3-meth-
yl-10-pentyloxecin-2-one (54): [α]2D8 = –5.8 (c = 0.7, CHCl3). 1H
(Z,3S,4S,9S,10R)-3,4,7,8,9,10-Hexahydro-4,9-dihydroxy-3-methyl- NMR (400 MHz, CDCl3): δ = 5.49–5.29 (overlapped, 2 H), 4.72
10-pentyloxecin-2-one (48): [α]2D8 = +11.2 (c = 0.4, CHCl3). 1H
NMR (200 MHz, CDCl3): δ = 5.77 (ddd, J = 11.8, 4.2, 1.0 Hz, 1
H), 5.43 (dt, J = 8.8, 2.2 Hz, 1 H), 5.29–5.17 (m, 1 H), 5.16–5.14
(m, 1 H), 3.79–3.78 (m, 1 H), 3.05 (dq, J = 12.1, 3.6 Hz, 1 H), 2.74
(dt, J = 10.4, 2.2 Hz, 1 H), 4.51 (t, J = 9.2 Hz, 1 H), 3.86 (dt, J =
11.6, 3.6 Hz, 1 H), 2.61 (dq, J = 12.8, 3.8 Hz, 1 H), 2.39 (qd, J =
9.4, 6.2 Hz, 1 H), 2.04–1.84 (m, 2 H), 1.61–1.58 (m, 2 H), 1.42–
1.16 (m, 10 H), 0.85 (t, J = 6.7 Hz, 3 H) ppm. 13C NMR (50 MHz,
870
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Eur. J. Org. Chem. 2014, 860–871