162
B. A. Mayes et al. / Tetrahedron Letters 45 (2004) 157–162
2.04 mmol) in 1,4-dioxane (15 mL). The reaction mixture
(K): 150, Reflections measured: 6990, Independent reflec-
tions: 2416, Rint: 0.0004, Reflections used: 1887, sigma(I)
limit: 3.00, l: 0.145, Absorption type: multi-scan, Trans-
mission range: 0.94–0.96, Structure solution: Sir92, Struc-
ture refinement: CRYSTALS, Refined on F squared,
Hydrogen on carbon: riding, others: refined, Partially
was stirred for 4 h at room temperature. TLC (ethyl
acetate/cyclohexane, 1:1) indicated complete conversion of
startingmaterial ( Rf 0.6) to one product (Rf 0.0–0.1).
Amberlite IR-120 (H+) resin was added to the solution,
which was then stirred for 15 min. The resin was removed
by filtration and the filtrate was concentrated in vacuo to
give the crude azido acid (1.09 g, 95%), which was
dissolved in 1,4-dioxane (7 mL). Pentafluorophenol
(718 mg, 3.90 mmol) and EDCI.HCl (449 mg, 2.34 mmol)
were added and the reaction mixture was stirred at room
temperature under an atmosphere of argon. After 16 h,
TLC (ethyl acetate/cyclohexane, 1:1) indicated complete
conversion of the startingmaterial ( Rf 0.0–0.1) to a major
UV active product (Rf 0.65). The solvent was removed in
vacuo and the residue was dissolved in dichloromethane
(75 mL). The resultingsolution was washed with aqueous
sodium bicarbonate solution (5% w/v, 30 mL · 2) and the
aqueous layer was extracted with dichloromethane
(30 mL). The combined organic layers were washed with
citric acid solution (5% w/v, 40 mL). The organic layer was
dried (magnesium sulfate), filtered and the solvent re-
moved. The residue was purified by flash column chroma-
occupied water of solvation: 0.30, some disorder, Dqmin
:
)0.35, Dqmax: 0.36, R-factor: 0.039, Weighted R-factor:
0.094, Number of parameters: 249, Goodness of fit: 1.118.
22
34. Selected data for protected cyclic octamer 15: ½a +0.83
D
(c 0.6, CD3CN); mmax (thin film): 3428 cmÀ1 (N–H),
1677 cmÀ1 (C@O, amides I), 1527 cmÀ1 (C@O, amides
II); 1H and 13C NMR aþre given in Tables 1 and 2 MS m=z
(ES+): 2075.1 (M+NH4 , 100%), 2080.0 (M+Naþ, 95%);
MS m=z (ES+): 1040.2 ([M+H+Na]2þ, 50%), 1051.2
([M+NH4+Na]2þ, 100%); MS m=z Isotope distribution
(ES+): C96H152N8O40Na (M+Naþ) calcd 2080.0, 90%;
2081.0, 100%; 2082.0, 65%; 2083.0, 30%; 2084.0, 6%,
measured 2079.0, 90%; 2080.0, 100%; 2081.0, 55%; 2082.0,
25%; 2083.0, 5%; 2084.0, 3%; MS m=z Isotope distribution
(ES+): C96H156N9O40 (M+NHþ4 ) calcd 2075.0, 90%;
2076.0, 100%; 2077.1, 65%; 2078.1, 30%; 2079.1, 6%,
measured 2074.1, 80%; 2075.1, 95%; 2076.1, 55%; 2077.1,
30%; 2078.1, 7%.
tography (ethyl acetate/cyclohexane, 1:4) to yield the
25
D
dimeric PFP ester 11 (1.32 g, 94%) as a colourless oil, ½a
35. Mayes, B. A.; Stetz, R. J. E.; Ansell, C. W. G.; Fleet, G.
+2.8 (c 1.3, CDCl3); mmax (thin film): 3428 cmÀ1 (N–H),
2105 cmÀ1 (N3 stretch), 1797 cmÀ1 (C@O, CO2Pfp),
1681 cmÀ1 (C@O, amide I), 1520 cmÀ1 (C@O, amide II);
MS m=z (ES+): 725.25 (M+Hþ, 100%), 747.23 (M+Naþ,
85%); HRMS: C30H37N4O11F5Na (M+Naþ) calcd
747.2282, found 747.2277; C30H37N4O11F5 calcd: C 49.73%,
25
36. Data for deprotected cyclic tetramer 9: ½a +3.0 (c 0.2,
D
D2O); mp: >220 ꢁC, white solid darkened on heating
above 160 ꢁC; 1H NMR dH (500 MHz, D2O): 3.32 (4H,
0
0
dd, J1;1 13.6, J 7.5, 4 · H-1), 3.56 (4H, dd, J1 ;1 13.6, J 5.8,
4 · H-10), 3.63 (4H, dd, J3;4 9.5, J3;2 1.9, 4 · H-3), 3.93 (4H,
dd, J4;3 9.5, J4;5 1.8, 4 · H-4), 3.94 (4H, m, 4 · H-2), 4.41
(4H, d, J5;4 1.8, 4 · H-5); 13C NMR dC (125 MHz, D2O):
41.83 (4 · C-1), 68.86 (4 · C-2), 69.87 (4 · C-3), 71.47
(4 · C-4), 71.77 (4 · C-5), 176.21 (4 · CONH); MS m=z
(ES)): 707.25 ([M)H]À, 19%), 708.25 ([M)H]À, 58%),
709.26 ([M ) H]À, 100%); HRMS: C24H43N4O20 ([M)H]À)
H 5.15%, N 7.73%, found C 49.35%, H 4.97%, N 7.25%.
24
30. Selected data for protected cyclic dimer 12: oil, ½a +6.35
D
(c 3.1, CHCl3); mmax (thin film): 3349 cmÀ1 (N–H),
1682 cmÀ1 (C@O, amides I), 1520 cmÀ1 (C@O, amides
II); 1H and 13C NMR are given in Tables 1 and 2. MS m=z
(ES+): 515.26 (M+Hþ, 100%); HRMS: C24H39N2O10
(M+Hþ) calcd 515.2605, found 515.2603.
24
D
31. Selected data for protected cyclic tetramer 13: ½a )35.2
calcd 707.2471, found 707.2492.
21
D
(c 1.3, CHCl3); mp: >210 ꢁC; mmax (thin film): 3429 cmÀ1
(N–H), 1682 cmÀ1 (C@O, amides I), 1525 cmÀ1 (C@O,
amides II); 1H and 13C NMR are given in Tables 1 and 2.
MS m=z (ES+): 1029.60 (M+Hþ, 20%), 1051.55 (M+Naþ,
37. Selected data for protected cyclic trimer 17: ½a +3.2 (c
2.0, CDCl3); mmax (thin film): 3352 cmÀ1 (N–H), 1673 cmÀ1
(C@O, amides I), 1531 cmÀ1 (C@O, amides II); 1H and
13C NMR are given in Tables 1 and 2; MS m=z (ES+):
794.30 ([M+Na]þ, 100%); HRMS: C36H57N3O15Na
100%);
MS
m=z
Isotope
distribution
(ES+):
C48H76N4O20Na (M+Naþ) calcd 1051.50, 100%;
1052.50, 60%; 1053.50, 20%; 1054.50, 5%, measured
1051.55, 100%; 1052.51, 60%; 1053.53, 20%; 1054.61,
5%; C48H76N4O20 calcd C 56.02%, H 7.44%, N 5.44%,
found C 55.52%, H 7.91%, N 5.04%.
([M+Na]þ) calcd 794.3687, found 794.3693.
24
D
38. Selected data for protected cyclic pentamer 19: ½a )15.6
(c 1.0, CHCl3); mp: sinters 118–119 ꢁC, melts 120–121 ꢁC;
mmax (thin film): 3429 cmÀ1 (N–H), 1682 cmÀ1 (C@O,
amides I), 1528 cmÀ1 (C@O, amides II); 1H and 13C
NMR are given in Tables 1 and 2, MS m=z (ES+): 1308.10
([M+Na]þ, 100%); MS m=z Isotope distribution (ES+):
C60H95N5O25Na ([M+Na]þ) calcd 1308.6, 100%; 1309.6,
70%; 1310.6, 30%; 1311.6, 10%; 1312.6, 3%, measured
1308.9, 100%; 1309.9, 70%; 1310.9, 18%; 1311.9, 4%;
32. Data for deprotected cyclic dimer 8: ½a2D4: )45.2 (c 0.65,
H2O); mp: >220 ꢁC; fine, white solid darkened on heating;
mmax (thin film, Ge plate): 3348 cmÀ1 (O–H, N–H),
1644 cmÀ1 (C@O, amides I), 1544 cmÀ1 (C@O, amides
II); 1H NMR dH (500 MHz, D2O): 3.15 (2H, dd, J1;1 12.8,
0
J1;2 3.8, 2 · H-1), 3.32 (2H, a-br d, J3;4 8.6, 2 · H-3), 3.52–
3.55 (2H, br m, 2 · H-10), 3.87 (2H, dd, J4;3 8.6, J4;5 4.9,
2 · H-4), 3.97 (2H, br m, 2 · H-2), 4.22 (2H, d, J5;4 4.9,
2 · H-5); 13C NMR dC (125 MHz, D2O): 39.98 (2 · C-1),
67.50 (2 · C-2), 69.92 (2 · C-3), 70.46 (2 · C-4), 74.90
(2 · C-5), 174.07 (2 · CONH); MS m=z (ES)): 353.12
([M)H]À, 100%); HRMS: C12H21N2O10 ([M)H]À) calcd
353.1196, found 353.1193.
1312.9, 2%.
25
D
39. Selected data for protected cyclic decamer 20: ½a +0.55
(c 0.55, CD3CN); mmax (thin film): 3429 cmÀ1 (N–H),
1682 cmÀ1 (C@O, amides I), 1520 cmÀ1 (C@O, amides II);
1H and 13C NMR are given in Tables 1 and 2. MS m=z
(ES+): 2591.3 ([M+NH4]þ, 100%); MS m=z Isotope
distribution (ES+): C120H194N11O50 ([M+NH4]þ) calcd
2589.3, 70%; 2590.3, 100%; 2591.3, 80%; 2592.3, 40%;
2593.3, 20%; 2594.3, 8%, measured 2590.3, 68%; 2591.3,
100%; 2592.3, 80%; 2593.3, 38%; 2594.3, 8%; 2595.3, 5%.
40. Mayes, B. A.; Cowley, A. R.; Ansell, C. W. G.; Fleet, G.
33. Crystallographic data deposited at CCDC, reference no:
CCDC 218823. Crystal data: Size: 0.30 · 0.40 · 0.40,
Crystal system: Trigonal, Space group: P3121, a:
9.2689(1), b: 9.2689(1), c: 28.9539(6), Volume:
2154.24(6), Density: 1.65, 2hmax: 60.04, Radiation type:
ꢀ
Mo Ka, Wavelength: 0.710730 A, Diffractometer type:
Nonius KappaCCD, Scan type: Omega, Temperature
41. This work has been supported by a BBSRC CASE award
with Smith & Nephew [to B.A.M.].