References and Notes
Reviews on peptidomimetics:
<A NAME="RG27806ST-1A">1a</A>
Giannis A.
Kolter T.
Angew. Chem., Int. Ed. Engl.
1993,
32:
1244
<A NAME="RG27806ST-1B">1b</A>
Gante J.
Angew. Chem., Int. Ed. Engl.
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33:
1699
<A NAME="RG27806ST-1C">1c</A>
Venkatesan N.
Kim BH.
Curr. Med. Chem.
2002,
9:
2243
<A NAME="RG27806ST-1D">1d</A>
Tourwe D.
Synthesis of Peptides and Peptidomimetics, In Methods of Organic Chemistry (Houben-Weyl)
Vol. E22c:
Goodman M.
Felix A.
Moroder L.
Toniolo C.
Thieme Verlag;
Stuttgart, New York:
2004.
<A NAME="RG27806ST-2A">2a</A>
Hann MM.
Sammes PG.
Kennewell PD.
Taylor JB.
J. Chem. Soc., Chem. Commun.
1980,
234
<A NAME="RG27806ST-2B">2b</A>
Hann MM.
Sammes PG.
Kennewell PD.
Taylor JB.
J. Chem. Soc., Perkin Trans. 1
1982,
307
<A NAME="RG27806ST-2C">2c</A>
Kranz M.
Kessler H.
Tetrahedron Lett.
1996,
37:
5359
For recent examples, see:
<A NAME="RG27806ST-3A">3a</A>
Otaka A.
Katagiri F.
Kinoshita T.
Odagaki Y.
Oishi S.
Tamamura H.
Hamanaka N.
Fujii N.
J. Org. Chem.
2002,
67:
6152
<A NAME="RG27806ST-3B">3b</A>
Oishi S.
Kamano T.
Niida A.
Odagaki Y.
Hamanaka N.
Yamamoto M.
Ajito K.
Tamamura H.
Otaka A.
Fujii N.
J. Org. Chem.
2002,
67:
6162
<A NAME="RG27806ST-3C">3c</A>
Tamamura H.
Hiramatsu K.
Miyamoto K.
Omagari A.
Oishi S.
Nakashima H.
Yamamoto N.
Kuroda Y.
Nakagawa T.
Otaka A.
Fujii N.
Bioorg. Med. Chem. Lett.
2002,
12:
923
<A NAME="RG27806ST-3D">3d</A>
Vasbinder MM.
Miller SJ.
J. Org. Chem.
2002,
67:
6240
<A NAME="RG27806ST-3E">3e</A>
Tamamura H.
Koh Y.
Ueda S.
Sasaki Y.
Yamasaki T.
Aoiki M.
Maeda K.
Watai Y.
Arikuni H.
Otaka A.
Mitsuya H.
Fujii N.
J. Med. Chem.
2003,
46:
1764
<A NAME="RG27806ST-3F">3f</A>
Wang XJ.
Hart SA.
Xu B.
Mason MD.
Goodell JR.
Etzkorn FA.
J. Org. Chem.
2003,
68:
2343
<A NAME="RG27806ST-3G">3g</A>
Garbe D.
Sieber S.
Bandur NG.
Koert U.
Marahiel MA.
ChemBioChem
2004,
5:
1000
<A NAME="RG27806ST-3H">3h</A>
Wipf P.
Xiao J.
Org. Lett.
2005,
7:
103
<A NAME="RG27806ST-3I">3i</A>
Bandur NG.
Harms K.
Koert U.
Synlett
2005,
773
<A NAME="RG27806ST-3J">3j</A>
Fu Y.
Bieschke J.
Kelly JW.
J. Am. Chem. Soc.
2005,
127:
15366
<A NAME="RG27806ST-3K">3k</A>
Reginato G.
Gaggini F.
Mordini A.
Valacchi M.
Tetrahedron
2005,
61:
6791
<A NAME="RG27806ST-4">4</A>
Gage JR.
Evans DA.
Org. Synth.
1989,
68:
77
<A NAME="RG27806ST-5">5</A>
Blakemore PR.
Cole WJ.
Kocieński PJ.
Morley A.
Synlett
1998,
26
<A NAME="RG27806ST-6">6</A>
Analytical Data of Sulfone 4.
R
f
= 0.11 (cHex-TBME, 2:1); [α]D
27 -9.1 (c 1.23, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.67-7.53 (m, 5 H), 7.11-7.03 (m, 2 H), 6.99-6.89 (m, 3 H), 4.84-4.67 (m, 1
H), 4.13 (dd, J = 15.3, 9.1 Hz, 1 H), 3.97 (dd, J = 15.3, 3.6 Hz, 1 H), 3.11 (dd, J = 13.8, 7.0 Hz, 1 H), 3.04 (dd, J = 13.8, 6.8 Hz, 1 H), 1.33 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 156.8 (q, J = 38 Hz), 155.1, 153.6, 131.7, 129.75 (2 C), 129.72 (2 C), 129.3, 125.1 (2 C), 124.6
(2 C), 78.8, 57.5, 47.5, 38.7, 28.8 (3 C). IR (film): ν = 3323 (m), 2982 (m), 2932
(w), 1703 (s), 1559 (m), 1508 (m), 1354 (s), 1220 (m), 1156 (s), 899 (w), 879 (w),
764 (m), 689 (w), 639 (m), 522 (m) cm-1. HRMS (ESI): m/z calcd for C22H24F3N5NaO4S [M + Na+]: 534.1393; found: 534.1401.
<A NAME="RG27806ST-7">7</A>
Compound 5 was prepared from 3-(4-hydroxyphenyl)prop-ionic acid by the following sequence: 1.
i. BnCl, KI, K2CO3, acetone, reflux, 2 d; ii. NaOH, H2O, reflux, 2 d, 80%; 2. i. PvCl, TEA, -20 °C, 2 h; ii. (R)-4-benzyl-1,3-oxazolidin-2-one, LiCl, 12 h, r.t., 91%; 3. Pd(OH)2/C, H2 (1 atm), MeOH-EtOAc (1:1), 3 h, 99%; 4. TBDPSCl, imidazole, DMF, 0 °C to r.t., 12
h, 89%.
<A NAME="RG27806ST-8">8</A>
Preparation of Compound 6.
A solution of 5 (7.02 mmol, 3.96 g) in CH2Cl2 (40 mL) was cooled to 0 °C and TiCl4 (7.72 mmol, 0.85 mL) was added dropwise. After 5 min, diisopropylethyl amine (DIPEA,
8.01 mmol, 1.4 mL) was added whereupon the solution turned dark purple. After the
mixture was stirred at 0 °C for 1 h a solution of 1,3,5-trioxane (8.01 mmol, 0.72
g) in CH2Cl2 (5 mL) was added, followed by TiCl4 (7.37 mmol, 0.81 mL). The mixture was stirred for 3 h at 0-10 °C. Then, sat. NH4Cl solution (50 mL) was added and the layers were separated. After extraction with
additional CH2Cl2 (3 × 50 mL) the organic layers were pooled and washed subsequently with H2O (2 × 25 mL) and brine (50 mL). After drying with Na2SO4 and evaporation of solvents the residue was purified by flash column chromatography
on silica (300 g, TBME-pentane 1:2 to 1:1) to give compound 6 as a colorless oil (5.97 mmol, 3.55 g, 85%). R
f
= 0.37 (c-Hex-EtOAc, 1:1); [α]D
24 -75.0 (c 0.98, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.74-7.65 (m, 4 H), 7.43-7.26 (m, 9 H), 7.24-7.16 (m, 2 H), 6.96 (pd, J = 8.5 Hz, 2 H), 6.67 (pd, J = 8.5 Hz, 2 H), 4.44 (dddd, J = 9.4, 7.6, 3.5, 2.1 Hz, 1 H), 4.26-4.13 (m, 1 H), 4.03 (dd, J = 9.1, 2.1 Hz, 1 H), 3.90-3.70 (m, 2 H), 3.83 (dd, J = 8.2, 8.2 Hz, 1 H), 3.23 (dd, J = 13.5, 3.3 Hz, 1 H), 2.86 (dd, J = 13.4, 7.6 Hz, 1 H), 2.76 (dd, J = 13.4, 5.3 Hz, 1 H), 2.73 (dd, J = 13.3, 3.7 Hz, 1 H), 2.26 (br s, 1 H), 1.08 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 175.5, 154.3, 153.2, 135.5 (4 C), 135.2, 133.0, 133.0, 132.9, 130.5, 129.9
(2 C), 129.8 (2 C), 129.5 (2 C), 128.9 (2 C), 127.7 (2 C), 127.4, 119.6 (2 C), 66.0,
63.0, 55.5, 47.1, 37.9, 34.0, 26.5 (3 C), 19.4. IR (KBr): ν = 3506 (m, br), 3029 (w),
2930 (m), 2857 (m), 1780 (s), 1697 (s), 1510 (s), 1390 (m), 1350 (w), 1255 (s), 1210
(m), 1112 (m), 917 (m), 701 (s), 501 (m) cm-1. HRMS (ESI): m/z calcd for C28H35NSiNaO4 [M + Na+]: 500.2228; found: 500.2229.
<A NAME="RG27806ST-9">9</A>
No other stereoisomer was detected in the NMR spectra. For the assignment of the stereochemistry
of 6, see Figure
[1]
.
<A NAME="RG27806ST-10A">10a</A>
Evans DA.
Urpi F.
Somers TC.
Clark JS.
Bilodeau MT.
J. Am. Chem. Soc.
1990,
112:
8215
<A NAME="RG27806ST-10B">10b</A>
Takacs JM.
Jaber MR.
Vellekoop AS.
J. Org. Chem.
1998,
63:
2742
<A NAME="RG27806ST-11">11</A>
The crystal data of compound 6a has been deposited in the Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 616493. Crystal data: C21H23NO5, M = 369.40, orthorhombic, P212121, a = 7.0200(4) Å, b = 13.4213(10) Å, c = 19.5897(12) Å, α = 90°, β = 90°, γ = 90°, V = 1845.7(2) Å3, Z = 4, D
calcd = 1.329 g/cm3, 16972 collected reflections, 3696 independent (R
int = 0.0390), R1 = 0.0265, wR2 = 0.0686 (all data).
<A NAME="RG27806ST-12">12</A>
Preparation of Compound 9.
A solution of sulfone 4 (0.17 mmol, 85 mg) in 1,2-dimethoxyethane (DME, 1 mL) was cooled to -78 °C and NaHMDS
(2 M in THF, 0.37 mmol, 0.18 mL) was added. The resulting yellow solution was stirred
at -78 °C for 30 min and aldehyde 8 dissolved in DME (0.5 mL) was added. The solution allowed to warm to r.t. overnight.
Then phosphate buffer (1 M, 2 mL) and TBME (4 mL) were added. After the layers were
separated the aqueous layer was extracted with additional TBME (3 × 4 mL). The combined
organic extracts were dried with Na2SO4 and after evaporation of solvents the residue was purified by flash column chromatography
(8 g, TBME-pentane, 1:10) followed by a second chromatography (8 g, acetone-pentane,
1:10). The pure product 9 was obtained as a colorless oil. The determination of the E/Z selectivity of 2.3:1 and the separation of the isomers was done after THP deprotection
affording compound 10.
E
-Isomer: R
f
= 0.41 (c-Hex-EtOAc, 1:1); [α]D
25 -31.2 (c 1.06, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.05-6.84 (m, 8 H), 6.23 (br d, J = 7.2 Hz, 1 H), 5.33 (dd, J = 15.2, 7.3 Hz, 1 H), 5.25 (dd, J = 15.4, 7.3 Hz, 1 H), 4.59 (ddd, J = 13.8, 7.0, 6.8 Hz, 1 H), 3.51 (dd, J = 10.6, 4.6 Hz, 1 H), 3.34 (dd, J = 10.3, 7.3 Hz, 1 H), 2.80 (dd, J = 13.6, 6.4 Hz, 1 H), 2.75 (dd, J = 13.0, 7.7 Hz, 1 H), 2.64 (dd, J = 12.9, 5.8 Hz, 1 H), 2.54-2.34 (m, 1 H), 2.49 (dd, J = 12.7, 8.0 Hz, 1 H), 1.67 (br s, 1 H), 1.32 (s, 9 H), 1.31 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 156.3 (q, J = 37 Hz), 154.5, 153.7, 134.6, 134.1, 131.0, 129.9, 129.7 (2 C), 129.5 (2 C), 124.3
(2 C), 124.0 (2 C), 117.7, 78.5, 78.2, 64.9, 53.2, 47.1, 40.1, 36.7, 28.82 (3 C),
28.80 (3 C). HRMS (ESI): m/z calcd for C29H38F3NNaO4 [M + Na+]: 544.2645; found: 544.2655.
Z
-Isomer: R
f
= 0.42 (c-Hex-EtOAc, 1:1); [α]D
24 +25.2 (c 1.04, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.07-6.82 (m, 8 H), 6.39 (br d, J = 6.0 Hz, 1 H), 5.41 (dd, J = 10.8, 10.4 Hz, 1 H), 5.31 (dd, J = 10.8, 9.0 Hz, 1 H), 4.59 (ddd, J = 14.4, 7.9, 7.0 Hz, 1 H, 5-H), 3.70 (dd, J = 10.5, 4.4 Hz, 1 H), 3.41 (dd, J = 10.1, 9.5 Hz, 1 H), 3.06-2.92 (m, 1 H), 2.63 (dd, J = 13.4, 5.1 Hz, 1 H), 2.37 (dd, J = 13.9, 7.3 Hz, 1 H), 2.30 (dd, J = 13.9, 6.0 Hz, 1 H), 2.25 (dd, J = 13.5, 9.2 Hz, 1 H), 1.70 (br s, 1 H), 1.29 (s, 9 H), 1.23 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 156.8 (q, J = 37 Hz), 154.6, 153.7, 135.1, 134.3, 130.3, 129.7, 129.6 (2 C), 129.5 (2 C), 124.4
(2 C), 124.0 (2 C), 117.5, 78.5, 78.2, 65.9, 49.3, 43.8, 39.4, 37.2, 28.8 (3 C), 28.7
(3 C). HRMS (ESI): m/z calcd for C29H38F3NNaO4 [M + Na+]: 544.2645; found: 544.2651.
<A NAME="RG27806ST-13">13</A>
De Mico A.
Margarita R.
Parlani L.
Vescovi A.
Piancatelli G.
J. Org. Chem.
1997,
62:
6974
<A NAME="RG27806ST-14">14</A>
Analytical Data of Compound 11.
R
f
= 0.24 (c-Hex-EtOAc, 1:1); [α]D
19 -30.7 (c 0.32, CHCl3). 1H NMR (500 MHz, 343 K, DMSO-d
6): δ = 11.98 (br s, 1 H), 7.85 (pd, J = 7.6 Hz, 2 H), 7.63 (pd, J = 7.6 Hz, 2 H), 7.40 (pt, J = 7.4 Hz, 2 H), 7.31 (pt, J = 7.4 Hz, 2 H), 7.25-7.11 (m, 1 H), 7.05 (pd, J = 8.3 Hz, 2 H), 7.03-6.97 (m, 2 H), 6.83 (pd, J = 8.5 Hz, 2 H), 6.78 (pd, J = 8.5 Hz, 2 H), 5.57-5.42 (m, 2 H), 4.28-4.17 (m, 2 H), 4.15-4.07 (m, 1 H), 4.14
(t, J = 6.8 Hz), 3.17-3.06 (m, 1 H), 2.90 (dd, J = 13.7, 7.6 Hz, 1 H), 2.69-2.57 (m, 3 H), 1.26 (s, 9 H), 1.22 (s, 9 H). 13C NMR (500 MHz, 343 K, DMSO-d
6): δ = 177.4, 153.2, 153.1 (2 C), 143.61, 143.59, 140.4 (2 C), 133.1, 132.64, 132.58,
129.3 (2 C), 129.1 (2 C), 127.3, 127.1 (2 C), 126.6 (2 C), 124.7 (2 C), 122.7 (2 C),
122.6 (2 C), 119.6 (2 C), 77.2, 77.1, 65.1, 53.6, 49.6, 46.5, 37.0, 28.28 (3 C), 28.26
(3 C); one benzylic carbon atom was not observed because of a superposition with the
DMSO-d
6 signal. HRMS (ESI): m/z calcd for C42H47NNaO6 [M + Na+]: 684.3296; found: 684.3313.