References and Notes
-
For examples see:
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1a
Gignoux C.
Newton AF.
Barthelme A.
Lewis W.
Alcaraz M.-L.
Stockman RA.
Org. Biomol. Chem.
2012,
10:
67
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1b
Roe SJ.
Aggarwal P.
Stockman RA.
Synthesis
2009,
3375
-
1c
Legeay
J.-C.
Lewis W.
Stockman RA.
Chem.
Commun.
2009,
2207
-
1d
Roe SJ.
Stockman RA.
Chem. Commun.
2008,
3432
-
1e
Newton AF.
Rejzek M.
Alcaraz M.-L.
Stockman RA.
Beilstein
J. Org. Chem.
2008,
4:
No.
4
-
1f
Karatholuvhu MS.
Sinclair A.
Newton AF.
Alcaraz M.-L.
Stockman RA.
Fuchs PL.
J.
Am. Chem. Soc.
2006,
128:
12656
- 2
Spande TF.
Jain P.
Garraffo HM.
Pannell LK.
Yeh HJC.
Daly JW.
Fukumoto S.
Inamura K.
Tokuyama T.
Torres JA.
Snelling RR.
Jones TH.
J.
Nat. Prod.
1999,
62:
5
- 3
Daly JW.
Witkop B.
Tokuyama T.
Nishikawa T.
Karle IL.
Helv.
Chim. Acta
1977,
60:
1128
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4a For
isolation of lepadins (+)-F, (+)-G, and (+)-H,
see: Davis RA.
Carroll AR.
Quinn RJ.
J.
Nat. Prod.
2002,
65:
454
-
4b For isolation of lepadins
(+)-D, (-)-E, and (-)-F, see: Wright AD.
Goclik E.
Koening GM.
Kaminsky R.
J.
Med. Chem.
2002,
45:
3067
-
4c For isolation of (-)-lepadin
A, see: Steffan B.
Tetrahedron
1991,
47:
8729
-
4d For isolation of lepadins
(-)-B and (-)-C, see: Kubanek J.
Williams DE.
de Silva ED.
Allen T.
Andersen
RJ.
Tetrahedron Lett.
1995,
36:
6189
- 5
Robbins D.
Newton AF.
Gignoux C.
Legeay J.-C.
Sinclair A.
Rejzek M.
Laxton CA.
Yalamanchili SK.
Lewis W.
O’Connell M.
Stockman RA.
Chem. Sci.
2011,
2:
2232
6
Representative
Procedure; Synthesis of 2a: To a solution of (2E,11E)-diethyl
7-oxotrideca-2,11-dienedioate (100 mg, 0.32 mmol) in CH2Cl2 (10
mL) at -10 ˚C was added TiCl4 (1 M
soln in CH2Cl2, 0.64 mL, 0.64 mmol). The mixture
was stirred at -10 ˚C for 30 min, then aniline
(40.0 µL, 0.48 mmol) was added. The mixture was allowed
to warm to r.t., then heated to reflux overnight. The reaction was
quenched with sat. aq NaHCO3 (10 mL) and filtered through
a pad of Celite. The filtrate was extracted with EtOAc (3 × 10
mL), the combined organics washed with brine (20 mL), dried over
anhyd Na2SO4 and concentrated in vacuo. The
resulting product was purified using column chromatography on silica gel
(PE-EtOAc, 6:1) to give the title compound as a yellow oil
(80.0 mg, 65%), as a 3:1 mixture of diastereomers (data for
major diastereomer detailed). IR (thin film): 3664, 3008, 1724 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 7.24-7.30
(m, 2 H), 6.96-7.06 (m, 3 H), 4.16-4.23 (m, 4
H), 4.04-4.15 (m, 1 H), 2.77 (ddd, J = 14.6,
9.6, 4.1 Hz, 1 H), 2.73-2.81 (m, 1 H), 2.59-2.72
(m, 2 H), 2.27-2.44 (m, 2 H), 1.78-1.93 (m, 3 H),
1.62-1.74 (m, 3 H), 1.45-1.61 (m, 3 H), 1.31 (t, J = 7.1 Hz, 3 H), 1.32 (t, J = 7.0 Hz, 3 H). ¹³C
NMR (100 MHz, CDCl3): δ = 173.5, 172.8,
149.2, 133.9, 128.7, 124.5, 122.5, 116.4, 60.4, 60.3, 58.0, 39.7,
38.7, 36.5, 29.7, 29.3, 28.1, 22.7, 21.0, 14.4, 14.3. MS (ES): m/z (%) = 386
(100) [M + 1], 408 (16). HRMS: m/z [M + H+] calcd
for C23H32NO4: 386.2326; found:
386.2335.
7 Data for major diastereomer of products: 2b: IR (thin film): 1730 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 7.22-7.35
(m, 5 H), 3.98-4.22 (m, 6 H), 3.42-3.53 (m, 1
H), 2.43-2.58 (m, 3 H), 2.19-2.34 (m, 3 H), 1.91-2.10
(m, 3 H), 1.58-1.70 (m, 4 H), 1.14-1.33 (m, 8
H). ¹³C NMR (100 MHz, CDCl3): δ = 173.7,
172.5, 140.6, 135.6, 128.3, 127.5, 126.7, 109.6, 60.26, 53.98, 52.82,
39.12, 37.18, 35.37, 27.84, 27.64, 23.91, 21.90, 19.42, 17.49, 14.64,
14.30. MS (ES): m/z (%) = 400 (100) [M + 1].
HRMS: m/z [M + H+] calcd
for C24H34NO4: 400.2482; found:
400.2429. 2g: IR (thin film): 1732, 1641,
1541 cm-¹. ¹H NMR
(300 MHz, CDCl3): δ = 5.70-5.90
(m, 1 H), 5.17 (d, J = 17.1
Hz, 1 H), 5.08 (d, J = 10.2
Hz, 1 H), 4.10-4.35 (m, 4 H), 3.50 (m, 3 H), 2.50 (m, 3 H),
2.25 (m, 3 H), 2.00 (m, 2 H), 1.80 (m, 2 H), 1.60 (m, 5 H), 1.35
(t, J = 7.2 Hz, 6 H). ¹³C
NMR (100 MHz, CDCl3): δ = 173.7, 172.6,
136.5, 134.9, 115.6, 106.5, 60.1, 60.0, 53.7, 53.1, 38.9, 36.8,
36.7, 28.3, 27.0, 24.6, 22.3, 20.2, 14.3, 14.2. MS (ES): m/z (%) = 350
(100) [M + 1]. HRMS: m/z [M + H+] calcd
for C20H32NO4: 350.2326; found:
350.2320. 2h: IR (thin film): 1730 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 4.12 (q, J = 7.2 Hz, 4 H), 4.80 (dd, J = 18.4, 2.4 Hz, 1 H), 3.67
(m, 1 H), 3.62 (dd, J = 18.4,
2.4 Hz, 1 H), 2.50-2.60 (m, 3 H), 2.25-2.35 (m,
4 H), 2.10 (m, 1 H), 1.90 (m, 1 H), 1.70 (m, 1 H), 1.55-1.65
(m, 5 H), 1.47 (m, 1 H), 1.17 (t, J = 7.1
Hz, 3 H), 1.15 (t, J = 7.1 Hz,
3 H). ¹³C NMR (100 MHz, CDCl3): δ = 173.6,
172.3, 133.7, 109.6, 81.2, 71.5, 60.2, 60.1, 54.4, 40.3, 38.8, 37.5,
36.7, 28.0, 26.9, 24.8, 22.5, 19.9, 14.3, 14.25. MS (ES): m/z (%) = 348
(100) [M + 1]. HRMS: m/z [M + H+] calcd
for C20H30NO4: 348.2175; found:
348.2135. 9: IR (thin film): 1598, 1490,
1446, 1302, 1144 cm-¹. ¹H NMR
(400 MHz, CDCl3): δ = 7.96 (t, J = 7.2 Hz, 2 H), 7.88 (t, J = 6.8 Hz, 1 H), 7.67 (m, 1
H), 7.50 (m, 6 H), 7.25 (m, 2 H), 6.95 (m, 3 H), 4.12 (t, J = 3.6 Hz, 1 H), 3.75 (dd, J = 14.2, 8.4 Hz, 1 H), 3.27
(dd, J = 14.2, 2.4 Hz, 1 H),
3.15 (m, 2 H), 2.68 (d, J = 5.6
Hz, 1 H), 2.20-2.40 (m, 2 H), 1.70-2.10 (m, 2
H), 1.48-1.65 (m, 6 H). ¹³C
NMR (100 MHz, CDCl3): δ = 148.0, 140.8,
139.8, 135.4, 133.8, 133.4, 129.4, 129.1, 128.9, 127.8, 127.6, 124.5,
123.4, 122.8, 117.6, 114.6, 58.6, 56.7, 56.5, 35.3, 28.4, 27.3,
26.7, 22.3, 21.9. MS (ES): m/z (%) = 522 (38.2) [M + 1].
HRMS: m/z [M + H+] calcd
for C29H32NO4S2: 522.1767;
found: 522.1755. 10: IR (thin film): 1725,
1601, 1498 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 7.26 (t, J = 8.0 Hz, 2 H), 6.89 (m, 1
H), 6.70 (t, J = 7.2 Hz, 1 H),
6.60 (d, J = 8.0 Hz. 1 H), 4.17
(q, J = 7.2 Hz, 2 H), 4.11 (q, J = 7.2 Hz, 2 H), 3.79-3.85
(m, 2 H), 2.58 (m, 3 H), 2.50 (m, 2 H), 2.44 (m, 2 H), 1.90 (m,
2 H), 1.29 (t, J = 7.2 Hz, 3
H), 1.23 (t, J = 7.2 Hz, 3 H). ¹³C
NMR (100 MHz, CDCl3): δ = 171.7, 171.0,
147.1, 129.4, 129.2, 128.8, 124.3, 122.1, 117.81, 113.4, 60.8, 60.2,
40.8, 39.6, 28.8, 25.6, 24.4, 14.25, 14.23. MS (ES): m/z (%) = 358
(100) [M + 1]. HRMS: m/z [M + H+] calcd
for C21H28NO4: 358.2013; found: 358.2015.
