J. S. Yadav, G. Rajendar
FULL PAPER
2-[(2R,4R,6R)-6-{[(2R,4R,6R)-6-Heptyl-2-phenyl-1,3-dioxan-4- 100.5, 100.6, 120.8, 126.0, 128.1, 128.1, 128.5, 128.6, 138.6, 138.9,
yl]methyl}-2-phenyl-1,3-dioxan-4-yl]-N-methoxy-N-methylacetamide
(5): Compound 5 was synthesized according to the procedure fol-
lowed for compound 15 and was obtained in 72% yield as a thick,
145.7, 166.7 ppm. MS (ESI): m/z = 537 [M + H]+, 559 [M +
Na]+. HRMS: calcd. for C33H44O6Na 559.3035; found 559.3063.
Polyrhacitide A (1): A solution of cis-enoate 3 (50 mg, 0.046 mmol)
in 80% AcOH (4 mL) was heated at 100 °C and stirred overnight.
The solvent was then removed under reduced pressure and traces
of acetic acid were removed azeotropically with toluene. Purifica-
tion by column chromatography (silica gel 60–120, CHCl3/MeOH,
98:2) yielded 1 (12.4 mg, 82%) as a white solid; m.p. 68–70 °C.
yellow oil. [α]3D0 = +4.2 (c = 1.1, CHCl ). IR (neat): ν = 2924, 2853,
˜
3
1635, 1452, 1343, 1115, 1025, 699 cm–1
.
1H NMR (300 MHz,
CDCl3): δ = 0.88 (t, J = 6.7 Hz, 3 H), 1.24–1.35 (m, 10 H), 1.42–
1.58 (m, 2 H), 1.6–1.8 (m, 2 H), 1.85–1.92 (m, 1 H), 2.08–2.20 (m,
1 H), 2.53–2.62 (m, 1 H), 2.94–3.03 (m, 1 H), 3.20 (s, 3 H), 3.66 (s,
3 H), 3.75–3.85 (m, 1 H), 4.05–4.18 (m, 2 H), 4.36–4.47 (m, 1 H),
5.52 (s, 1 H), 5.59 (s, 1 H), 7.29–7.41 (m, 6 H), 7.45–7.54 (m, 4
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.1, 22.6, 25.0, 29.2,
29.5, 29.7, 31.8, 35.9, 36.8, 36.8, 41.9, 61.4, 65.5, 72.8, 73.0, 73.5,
76.9, 100.5, 100.7, 126.0, 128.1, 128.4, 128.6, 129.0, 129.7, 138.5,
138.9, 171 ppm. MS (ESI): m/z = 540 [M + H]+, 562 [M + Na]+.
HRMS: calcd. for C32H45NO6Na 562.3144; found 562.3165.
[α]3D0 = +7.8 (c = 0.4, MeOH). IR (neat): ν = 3459, 2925, 2854,
˜
1729, 1384, 1220, 1076, 772, 677 cm–1 1H NMR (300 MHz,
.
CDCl3): δ = 0.88 (t, J = 6.7 Hz, 3 H), 1.24–1.42 (m, 9 H), 1.44–
1.76 (m, 8 H), 1.99–2.07 (m, 3 H), 2.77 (dd, J = 5.1, 19.2 Hz, 1 H),
2.88 (d, J = 19.2 Hz, 1 H), 3.76–3.82 (m, 1 H, 11-H), 4.0–4.07 (m,
2 H, 7-,9-H), 4.38 (br. s, 1 H, 3-H), 4.83–4.86 (m, 1 H, 5-H) ppm.
13C NMR (75 MHz, CDCl3): δ = 14.3, 22.8, 25.5, 29.4, 29.7, 29.7,
31.9, 36.5, 37.4, 37.9, 43.1, 43.5, 66.1, 67.0, 72.0, 72.1, 72.6,
168.2 ppm. MS (ESI): m/z = 329 [M + H]+, 351 [M + Na]+.
HRMS: calcd. for C18H32O5Na 351.2147; found 351.2160.
2-[(2R,4R,6R)-6-{[(2R,4R,6R)-6-Heptyl-2-phenyl-1,3-dioxan-4-
yl]methyl}-2-phenyl-1,3-dioxan-4-yl]acetaldehyde (19): DIBAL-H
(0.32 mL, 0.44 mmol, 20% in toluene) was carefully added to a
stirred solution of amide 5 (120 mg, 0.22 mmol) in dry THF (8 mL)
at –78 °C under an inert atmosphere. The reaction was monitored
by TLC and after 30 min it was quenched with a sat. aqueous po-
tassium sodium tartrate solution. Stirring was continued for 2 h
(until a clear solution formed), the organic layer was separated,
and the aqueous layer was washed with EtOAc (2ϫ 5 mL). The
combined organic layers were washed with water and brine, dried
with anhydrous sodium sulfate, and concentrated in vacuo to yield
aldehyde 19 (89 mg, 83%) as a clear sticky oil. Compound 19 was
used directly in the next step without any purification. [α]3D0 = –3.4
(c = 1.3, CHCl3), 1H NMR (300 MHz, CDCl3): δ = 0.88 (t, J =
6.9 Hz, 3 H), 1.24–1.36 (m, 10 H), 1.44–1.60 (m, 4 H), 1.63–1.83
(m, 2 H), 2.08–2.22 (m, 1 H), 2.63 (dd, J = 4.9, 16.8 Hz, 1 H), 2.83
(ddd, J = 1.7, 7.1, 15.1 Hz, 1 H), 3.77–3.87 (m, 1 H), 4.01–4.22 (m,
2 H), 4.38–4.48 (m, 1 H), 5.53 (s, 1 H), 5.59 (s, 1 H), 7.31–7.41 (m,
6 H), 7.45–7.55 (m, 4 H), 9.85 (s, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 14.0, 22.6, 25.0, 29.2, 29.5, 29.7, 31.8, 35.9, 35.9, 36.4,
36.8, 41.6, 49.3, 71.8, 73.0, 73.1, 76.9, 100.5, 100.7, 126.0, 126.0,
128.1, 128.2, 128.5, 128.8, 138.2, 138.8, 200.3 ppm. MS (ESI): m/z
= 481 [M + H]+. HRMS: calcd. for C30H41O5 481.2953; found
481.2942.
1-[(2R,4R,6R)-6-{[(2R,4R,6R)-6-Heptyl-2-phenyl-1,3-dioxan-4-
yl]methyl}-2-phenyl-1,3-dioxan-4-yl]pent-4-en-2-one (21): Com-
pound 21 was synthesized according to the procedure followed for
the synthesis of compound 6. Compound 21 was obtained in 91%
yield. [α]3D0 = –5.7 (c = 1.5, CHCl ). IR (neat): ν = 2924, 2853, 1713,
˜
3
1635, 1455, 1386, 1113, 1019, 699 cm–1
.
1H NMR (300 MHz,
CDCl3): δ = 0.88 (t, J = 6.4 Hz, 3 H), 1.22–1.34, (m, 10 H), 1.41–
1.56 (m, 3 H), 1.58–1.71 (m, 3 H), 1.72–1.81 (m, 1 H), 1.84–1.94
(m, 1 H), 2.59 (dd, J = 6.9, 16.4 Hz, 1 H), 3.24 (d, J = 6.9 Hz, 2
H), 3.50–3.64 (m, 1 H), 3.75–3.86 (m, 1 H), 4.01–4.86 (m, 2 H),
4.28–4.42 (m, 1 H), 5.07–5.22 (m, 2 H), 5.52 (s, 1 H), 5.55 (s, 1 H),
5.82–5.97 (m, 1 H), 7.28–7.40 (m, 6 H), 7.42–7.55 (m, 4 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 14.0, 22.6, 25.0, 29.2, 29.5, 29.6,
31.8, 35.9, 36.8, 41.7, 48.1, 48.8, 73.0, 73.3, 74.4, 76.9, 100.5, 100.5,
119.1, 126.0, 126.0, 128.1, 128.2, 128.5, 128.6, 130.1, 138.4, 138.8,
206.3 ppm. MS (ESI): m/z = 521 [M + H]+, 543 [M + Na]+.
HRMS: calcd. for C33H44O5Na 543.3086; found 543.3078.
(S)-1-[(2S,4S,6S)-6-{[(2R,4R,6R)-6-Heptyl-2-phenyl-1,3-dioxan-4-
yl]methyl}-2-phenyl-1,3-dioxan-4-yl]pent-4-en-2-ol (4): LiI (463 mg,
3.4 mmol) was added to a stirred solution of alkoxy ketone 21
Ethyl (Z)-4-[(2S,4S,6S)-6-{[(2R,4R,6R)-6-Heptyl-2-phenyl-1,3-di- (60 mg, 0.11 mmol) in dry diethyl ether (40 mL) at –40 °C and the
oxan-4-yl]methyl}-2-phenyl-1,3-dioxan-4-yl]but-2-enoate (3): Ethyl mixture was stirred for a further 30 min. Then the mixture was
2-[bis(2,2,2-trifluoroethoxy)phosphoryl]acetate (101 mg,
cooled to –100 °C and, after 5 min, LiAlH4 (131 mg, 3.4 mmol)
0.32 mmol) in THF (2 mL) was added to a stirred solution of NaH was added in one portion and the mixture was stirred at –100 °C
(12.8 mg, 60% w/w in paraffin, 0.32 mmol) at –78 °C. The mixture for 45 min. The reaction mixture was quenched with 10% aqueous
was stirred for 1 h at –78 °C ad then a solution of aldehyde 19
(120 mg, 0.25 mmol) in THF (1 mL) was added dropwise. The re-
sulting mixture was stirred for 45 min and the reaction was
quenched with saturated sodium hydrogencarbonate and warmed
to room temperature. The layers were separated and the aqueous
layer was extracted with diethyl ether. The combined organic layers
were washed with brine and dried with anhydrous sodium sulfate.
Removal of the solvent and separation of the diastereomers by sil-
ica gel chromatography yielded 3 (121 mg, 90%) as a thick, light-
potassium sodium tartrate solution and stirring was continued until
a clear solution formed. The organic layer was separated and the
aqueous layer extracted with EtOAc (2ϫ 10 mL). The combined
organic layers were washed with brine, dried with anhydrous so-
dium sulfate, and concentrated in vacuo. Purification by column
chromatography (silica gel, hexane–EtOAc 95:5) gave homoallylic
alcohol 4 (57 mg, 95%) as a clear liquid. [α]3D0 = –4.4 (c = 1.2,
CHCl ). IR (neat): ν = 3445, 2923, 2852, 2361, 1633, 1459, 1118,
˜
3
1029, 768 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 0.88 (t, J =
yellow oil. [α]3D0 = –11 (c = 1.4, CHCl ). IR (neat): ν = 2923, 2854,
7.3 Hz, 3 H), 1.24–1.34 (m, 10 H), 1.43–1.56 (m, 3 H), 1.56–1.85
˜
3
2362, 1723, 1647, 1458, 1179, 1018, 759, 696 cm–1
.
1H NMR (m, 5 H), 2.10–2.18 (m, 1 H), 2.23–2.30 (m, 2 H), 3.52–3.64 (br. s,
(300 MHz, CDCl3): δ = 0.88 (t, J = 7.1, 13.4 Hz, 3 H), 1.24–1.34 1 H), 3.77–3.83 (m, 1 H), 3.95–4.0 (m, 1 H), 4.01–4.09 (m, 1 H),
(m, 10 H), 1.42–1.81 (m, 7 H), 2.09–2.22 (m, 1 H), 2.86–2.97 (m, 4.10–4.16 (m, 2 H), 5.09–5.15 (m, 2 H), 5.51 (s, 0.5 H), 5.58 (s, 0.5
1 H), 3.04–3.16 (m, 1 H), 3.71 (s, 3 H), 3.76–3.86 (m, 1 H), 3.94– H), 5.80–5.89 (m, 1 H), 7.3–7.39 (m, 6 H), 7.46 (d, J = 6.4 Hz, 2
4.16 (m, 3 H), 5.52 (s, 1 H), 5.54 (s, 1 H), 5.90 (d, J = 11.5 Hz, 1
H), 7.50 (d, J = 8.2 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ
H), 6.42–6.53 (m, 1 H), 7.31–7.40 (m, 6 H), 7.47–7.53 (m, 4 = 14.0, 22.6, 25.0, 29.2, 29.5, 29.6, 31.8, 35.9, 36.8, 41.7, 41.9, 60.3,
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.1, 22.6, 25.0, 29.2,
70.2, 73.0, 73.2, 76.9, 77.2, 100.5, 100.6, 117.6, 125.9, 126.0, 128.1,
29.7, 31.8, 35.1, 35.9, 36.3, 36.9, 41.8, 51.0, 73.0, 73.1, 75.9, 76.9,
128.2, 128.5, 128.8, 134.6, 138.2, 138.8 ppm. MS (ESI): m/z = 545
6786
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Eur. J. Org. Chem. 2011, 6781–6788