Non-Phenolic Dicinnamamides From Pholiota Spumosa
Pholiotic Acid {(2R)-2-[(S)-3-Hydroxy-3-methylglutaryloxy]putres-
cine Dicinnamamide; 5}: Waxy solid. [α]2D2 = +18.5 (c = 0.4, MeOH).
1H and 13C NMR (CD3OD), see Tables 1 and 2, respectively. 1H
NMR (400 MHz, [D6]DMSO): δ = 8.40 (m, 1 H, NH), 8.11 (br. t,
1 H, NH), 7.55–7.51 (m, 4 H, Ar), 7.49–7.40 (m, 8 H, Ar, 3Ј-H and
3ЈЈ-H), 6.67 (d, J = 14.6 Hz, 1 H, 2Ј-H or 2ЈЈ-H), 6.58 (d, J =
14.6 Hz, 1 H, 2ЈЈ-H or 2Ј-H), 4.89 (m, 1 H, 2-H), 3.45 (m, 2 H, 1-
(S)-2-(Triisopropylsilyloxy)butane-1,4-diol (7):
A
solution of
DIBAL-H (1 in CH2Cl2, 31.2 mL, 5.2 equiv.) was added drop-
wise to compound 6 (1.9 g, 6.0 mmol) in CH2Cl2 (5 mL) under a
N2 flow at –15 °C, and the disappearance of 6 was monitored by
GC. After 3 h, the reaction mixture was quenched by adding 1-
propanol (6 mL) and H2O (3 mL) and then partitioned between
an aqueous saturated solution of NH4Cl (10 mL) and 2-butanone
H), 3.21 (m, 2 H, 4-H), 2.57 (ABq, 2 H, 2ЈЈЈ-H or 4ЈЈЈ-H), 2.41 (20 mL). The organic layer was washed with H2O (5 mL) and dried
(ABq, 2 H, 4ЈЈЈ-H or 2ЈЈЈ-H), 1.73 (m, 2 H, 3-H), 1.27 (s, 3 H, 6ЈЈЈ- with anhydrous Na2SO4; the solvent was evaporated under vacuum
H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 173.0 (s, C-5ЈЈЈ),
170.4 (s, C-1ЈЈЈ), 165.3 (s, C-1Ј or C-1ЈЈ), 165.0 (s, C-1ЈЈ or C-1Ј),
to afford pure diol 7 (1.34 g, 86%) as a viscous liquid. [α]2D2 = –7.3
(c = 4.2, MeOH). 1H NMR (400 MHz, CD3CN): δ = 4.12 (m, 1
139.0 (d, C-3Ј or C-3ЈЈ), 138.6 (d, C-3ЈЈ or C-3Ј), 135.0 (s, 2 C, C- H, 2-H), 3.80 (m, 2 H, 1-H), 3.70 (m, 2 H, 4-H), 1.93 (m, 2 H, 3-
4Ј and C-4ЈЈ), 129.5 (d, 4 C, Ar), 129.0 (d, 2 C, Ar), 127.6 (d, 4 C, H), 1.30 [m, 3 H, 3ϫCH(CH3)2], 1.16 [br., 18 H, 3ϫCH(CH3)2]
Ar), 122.3 (d, C-2Ј or C-2ЈЈ), 122.1 (d, C-2ЈЈ or C-2Ј), 70.8 (d, C- ppm. 13C NMR (100 MHz, CD3CN): δ = 72.0 (t, C-1), 66.5 (d, C-
2), 69.2 (s, C-3ЈЈЈ), 46.0 (t, 2 C, C-2ЈЈЈ and C-4ЈЈЈ), 41.3 (t, C-1),
2), 58.9 (t, C-4), 38.2 (t, C-3), 18.5 [q, 6 C, 3ϫCH(CH3)2], 13.2 [d,
35.3 (t, C-4), 31.3 (t, C-3), 27.6 (q, C-6ЈЈЈ) ppm. IR (thin film): ν
3 C, 3ϫCH(CH3)2] ppm. MS (ESI+): m/z = 285.2 [M + Na]+.
˜
= 3700–2400 (br., COOH stretching), 3308, 3077, 2924, 2851, 1723,
1714, 1659, 1620, 1614, 1556, 1449, 1343, 1226, 1079, 1028,
978 cm–1. UV (MeOH): λ (ε, Lmol–1 cm–1): 274.5 (9000), 216.5
(6800) nm. CD (MeOH): λ (∆ε) = 331.0 (+0.06), 268.5 (+0.29),
220.0 (–0.47) nm. MS (ESI–): m/z = 507.4 [M – H]–. MS (ESI+,
HCOOH added): m/z = 509.6 [M + H]+, 531.2 [M + Na]+. MS
(EI): m/z (%) = 448 (1) [M – CH3COOH]+, 407 (4), 406 (5), 405
(3), 259 (10), 199 (65), 131 (100), 103 (71), 77 (46). HRMS (ESI+):
(S)-2-(Triisopropylsilyloxy)butane-1,4-diol Ditosylate (8): Com-
pound 7 (1.34 g, 5.1 mmol) in dry MeCN (3 mL) was added drop-
wise to p-toluenesulfonyl chloride (5 g, 26 mmol) in CH2Cl2 (6 mL)
to which dry pyridine (1.5 mL) had been previously added. The
reaction mixture was stirred for 1 h at 5 °C, followed by an ad-
ditional hour at r.t., and then quenched by adding H2O (10 mL).
The aqueous phase was extracted with CH2Cl2 (2ϫ10 mL). The
organic layers were collected, dried with anhydrous Na2SO4 and
the solvents evaporated under vacuum. The resulting residue
(2.15 g) was chromatographed on a silica gel column deactivated
with Et3N (petroleum ether/CH2Cl2, 8.5:1.5 to 3:7) to afford 8
(1.2 g, 42%) as a colourless viscous liquid. [α]2D2 = –8.6 (c = 1.1,
MeOH). 1H NMR (400 MHz, CDCl3): δ = 7.74 (m, 4 H, Ar), 7.36–
7.32 (m, 4 H, Ar), 4.08 (m, 3 H, 1a-H, 2-H and 4a-H), 3.87 (m, 1
H, 4b-H), 3.82 (m, 1 H, 1b-H), 2.45 (s, 3 H, Ar-CH3), 2.44 (s, 3 H,
Ar-CH3), 1.83 (m, 2 H, 3-H), 0.92 [m, 3 H, 3ϫCH(CH3)2], 0.88
[br., 18 H, 3ϫCH(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δ =
145.2 (s, Ar), 145.0 (s, Ar), 132.9 (s, Ar), 132.7 (s, Ar), 130.0 (d, 2
C, Ar), 129.9 (d, 2 C, Ar), 128.1 (d, 2 C, Ar), 128.0 (d, 2 C, Ar),
72.1 (t, C-1), 66.9 (d, C-2), 66.3 (t, C-4), 33.5 (t, C-3), 27.7 (q, 2 C,
calcd. for C28H31N2O7 [M – H]– 507.21367; found 507.21325.
–
Methyl Pholiotate (5a): An ethereal solution of CH2N2 (0.4 mL)
was added dropwise to pholiotic acid (5; 8 mg) in MeOH (0.5 mL).
The resulting solution was evaporated under vacuum, and the resi-
due was chromatographed on a silica gel column (benzene/EtOAc,
2:1) to afford methyl pholiotate (5a; 4 mg) as a colourless oil.
1
[α]2D2 = +4.0 (c = 0.2, MeOH). H NMR (400 MHz, CD3OD): δ =
7.60–7.48 (m, 4 H, Ar), 7.41–7.34 (m, 8 H, Ar, 3Ј-H and 3ЈЈ-H),
6.61 (d, J = 15.8 Hz, 2 H, 2Ј-H and 2ЈЈ-H), 5.14 (m, 1 H, 2-H),
3.68 (m, 1 H, 1a-H), 3.64 (s, 3 H, COOCH3), 3.45 (m, 1 H, 1b-H),
3.39 (m, 2 H, 4-H), 2.74 (ABq, 2 H, 2ЈЈЈ-H or 4ЈЈЈ-H), 2.70 (ABq,
2 H, 4ЈЈЈ-H or 2ЈЈЈ-H), 1.89 (m, 2 H, 3-H), 1.41 (s, 3 H, 6ЈЈЈ-H)
ppm. 13C NMR (100 MHz, CD3OD): δ = 173.2 (s, C-5ЈЈЈ), 172.4
(s, C-1ЈЈЈ), 169.1 (s, C-1Ј or C-1ЈЈ), 168.9 (s, C-1ЈЈ or C-1Ј), 142.3
(d, C-3Ј or C-3ЈЈ), 142.1 (d, C-3ЈЈ or C-3Ј), 136.3 (d, 2 C, C-4Ј and
C-4ЈЈ), 130.1 (d, 4 C, Ar), 129.0 (d, 2 C, Ar), 122.4 (d, 4 C, Ar),
121.7 (d, C-2Ј or C-2ЈЈ), 121.6 (d, C-2ЈЈ or C-2Ј), 72.3 (d, C-2), 71.1
(s, C-3ЈЈЈ), 52.1 (q, COOCH3), 46.6 (t, C-2ЈЈЈ or C-4ЈЈЈ), 46.3 (t, C-
4ЈЈЈ or C-2ЈЈЈ), 43.4 (t, C-1), 37.1 (t, C-4), 32.5 (t, C-3), 26.1 (q, C-
6ЈЈЈ) ppm. MS (ESI+): m/z = 523 [M + H]+, 545 [M + Na]+.
2ϫAr-CH3), 18.0 [q,
6 C, 3ϫCH(CH3)2], 12.4 [br., 3 C,
3ϫCH(CH3)2] ppm. MS (ESI+): m/z = 593.16 [M + Na]+, 571.26
[M + H]+.
(S)-(1,4-Diazidobutyl-2-oxy)triisopropylsilane (9): Solid NaN3
(1.40 g, 21.6 mmol) was added portionwise to compound 8 (1.2 g,
2.16 mmol) in DMF (6 mL), and the reaction mixture was stirred
at 110 °C for 45 min. H2O (10 mL) was added, and the mixture
was extracted with EtOAc (2ϫ10 mL). The collected organic layers
were dried with anhydrous Na2SO4, and the solvent was evaporated
under vacuum at r.t. to yield diazide 9 (0.64 g, 95%), which was
immediately used in the next reaction.
Dimethyl (S)-(–)-2-(Triisopropylsilyloxy)butandioate (6): Triisopro-
pylsilyl chloride (3.86 g, 20 mmol) and imidazole (0.64 g, 9.5 mmol)
were added to dimethyl (S)-malate (1.5 g, 9.2 mmol) in DMF
(10 mL). The reaction mixture was stirred at r.t. for 27 h under a
N2 atmosphere. At the end, H2O (10 mL) was added, and the mix-
ture was extracted with CH2Cl2 (2ϫ10 mL). The organic layer was
dried with anhydrous Na2SO4, and the solvent was removed under
vacuum. The residue (5.6 g) was chromatographed on a silica gel
column deactivated with Et3N (toluene/CH2Cl2, 3:1) to afford the
protected dimethyl malate 6 (2.28 g, 78%) as a colourless viscous
liquid. [α]2D2 = –12.8 (c = 1.9, MeOH). 1H NMR (400 MHz,
(S)-(+)-2-(Triisopropylsilyloxy)butane-1,4-diamine
(10):
PPh3
(1.47 g, 5.61 mmol) dissolved in MeCN (5 mL) was added to a
solution of freshly prepared diazide 9 (0.64 g, 2.04 mmol) in MeCN
(5 mL) whilst stirring, and the resulting mixture was kept at 60 °C
for 1 h. Subsequently, H2O (3 mL) and 30% NH4OH (7 mL) were
added and stirring was continued at 60 °C for an additional hour.
The reaction mixture was cooled to r.t. and then was extracted with
EtOAc; the organic layer was dried with Na2SO4, and the solvent
CDCl3): δ = 4.72 (t, J = 6.2 Hz, 1 H, 2-H), 3.71 (s, 3 H, OCH3), was evaporated under vacuum. The residue was chromatographed
3.65 (s, 3 H, OCH3), 2.77 (d, J = 6.0 Hz, 1 H, 3a-H), 2.74 (d, J =
on an RP-18 column (H2O/MeOH, 2:3 to 1:9 + 1% acetic acid) to
6.0 Hz, 1 H, 3b-H), 1.13 [m, 3 H, 3ϫCH(CH3)2], 1.06 [br., 18 H, yield 10 (0.48 g, 91%) as a viscous liquid. [α]2D2 = +1.7 (c = 0.33,
3ϫCH(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δ = 173.3 (s, MeOH). 1H NMR (400 MHz, CD3OD): δ = 4.15 (m, 1 H, 2-H),
C-1), 171.3 (s, C-4), 70.1 (d, C-2), 52.6 (q, OCH3), 52.3 (q, OCH3), 2.91 (m, 1 H, 1a-H), 2.87 (m, 1 H, 1b-H), 2.82 (m, 1 H, 4a-H),
41.1 (t, C-3), 18.5 [q, 6 C, 3ϫCH(CH3)2], 13.2 [br., 3 C,
2.79 (m, 1 H, 4b-H), 1.86 (m, 1 H, 3a-H), 1.80 (m, 1 H, 3b-H), 1.15
[m, 3 H, 3ϫCH(CH3)2], 1.10 [d, J = 6.6 Hz, 18 H, 3ϫCH(CH3)2]
3ϫCH(CH3)2] ppm. MS (ESI+): m/z = 341.2 [M + Na]+.
Eur. J. Org. Chem. 2007, 5551–5559
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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