Nꢀ(αꢀPhosphonoalkyl)amino acids
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 4, April, 2007
803
Lꢀalaninate, the yield was 95%, Rf 0.62 (CHCl3—MeOH, 10 : 1),
(CHCl3—MeOH, 10 : 1). Found (%): C, 62.06; H, 8.72; N, 3.26.
C22H36NO5P. Calculated (%): C, 62.07; H, 8.55; N, 3.29.
1H NMR, δ: 0.35—0.50 (m, 4 Н, 2 CH2, cycl.); 0.85, 0.88
(both d, 3 H each, Me, JH,P = 16.6 Hz, JH,P = 16.2 Hz);
0.92—0.96, 1.12—1.18 (both m, 1 Н each, cycl.); 1.29, 1.30
(both t, 6 H, Me, 2 POEt, J = 7.0 Hz); 1.33, 1.34 (both s, 9 Н,
3 Me, But); 2.07 (br.s, 1 H, NH); 2.78—2.87 (m, 2 H, Phe);
3.91, 3.97 (both t, 2 H, Phe, J = 7.1 Hz, J = 7.0 Hz); 4.05—4.14
(m, 4 H, 2 OCH2); 7.19—7.27 (m, 5 H, arom.). 31P NMR, δ:
[α]23 –17 (CHCl3). Found (%): C, 59.35; H, 8.40; N, 3.65.
D
C19H32NO5P. Calculated (%): C, 59.17; H, 8.39; N, 3.65.
1H NMR, δ: 1.12, 1.17, 1.27, 1.37 (all t, 6 H each, 2 Me, POEt,
J = 7.0 Hz); 1.21, 1.25 (both d, 3 H each, Me, Ala, J = 7.0 Hz);
1.31, 1.41 (both s, 9 Н each, 3 CMe3); 1.68, 1.74 (both d,
3 H each, Me, 2JH,P = 16.3 Hz, 2JH,P = 16.7 Hz); 2.90 (br.s, 1 H,
NH); 2.97, 3.27 (both q, 1 H each, Ala, J = 6.9 Hz); 3.75—4.15
(m, 4 H, 2 OCH2); 7.18—7.36, 7.54—7.61 (both m, 5 H each,
arom.). 31P NMR, δ: 25.72. 13C NMR, δ: 16.18, 16.28 (both d,
2
2
27.17, 27.22. 13C NMR, δ: 0.25, 0.85 (both d, CH, cycl., 2JC,P
=
3
3
Me, POEt, JC,P = 5.4 Hz); 19.89, 20.86 (both s, Me, Ala);
9.40 Hz); 1.17, 1.67 (both d, 2 CH2, cycl., JC,P = 2.69 Hz);
14.76, 16.24 (both s, Me); 16.53, 16.58 (both d, Me, POEt,
3JC,P = 5.37 Hz); 27.79, 27.83 (both s, CMe3); 41.73, 42.21
21.29, 22.04 (both s, Me); 27.68, 27.75 (both s, CMe3); 51.51,
53.30 (both d, CH, Ala, J = 13.4 Hz, J = 13.4 Hz); 58.81, 59.99
(both d, C(1), 1JC,P = 150.4 Hz, 1JC,P = 155.8 Hz); 62.97—63.21
(m, OCH2); 80.49, 80.53 (both s, CMe3); 127.13, 127.83, 128.27,
(both s, CH2, Phe); 55.19, 55.32 (both d, C(1), 1JC,P = 157.1 Hz,
3
1JC,P = 158.5 Hz); 57.07, 57.31 (both d, CH, Phe, JC,P
=
140.31 (Carom.); 175.24, 175.35 (both s, C=O, Ala). IR, ν/cm–1
:
9.4 Hz, 3JC,P = 6.7 Hz); 61.99, 62.26, 62.30, 62.53 (all d, OCH2,
2
2
2
1250 (P=О); 1730 (C=O); 3340, 3450 (NH).
2JC,P = 8.06 Hz, JC,P = 6.72 Hz, JC,P = 8.06 Hz, JC,P
=
tertꢀButyl Nꢀ[1ꢀ(diethoxyphosphoryl)ꢀ1ꢀphenylethyl]phenylꢀ
alaninate (11) was obtained from acetophenone and tertꢀbutyl
Lꢀphenylalaninate, the yield was 80%, Rf 0.68 (CHCl3—MeOH,
10 : 1), [α]23 1.5 (CHCl3), [α]23 –4.0 (MeOH). Found (%):
6.72 Hz); 80.54, 80.66 (both s, CMe3); 126.29, 127.93, 129.69,
137.83, 138.07 (Carom.); 175.10, 175.35 (both s, C=O, Phe). IR,
ν/cm–1: 1250 (P=О); 1730 (C=O); 3340, 3470 (NH).
tertꢀButyl Nꢀ[1ꢀ(diethoxyphosphoryl)ꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ
1ꢀyl]alaninate (14)8 was obtained from indanꢀ1ꢀone and
tertꢀbutyl Lꢀalaninate, the yield was 80%, Rf 0.50
(CHCl3—MeOH, 10 : 1). Found (%): C, 60.44; H, 8.13; N, 3.45.
C20H32NO5P. Calculated (%): C, 60.44; H, 8.12; N, 3.52. IR,
ν/cm–1: 1250 (P=О); 1730 (C=O); 3320, 3470 (NH). The prodꢀ
uct was isolated as a mixture of diastereomers in a ratio of 3 : 7
(14а : 14b). The mixture was subjected to further column chroꢀ
matography on silica gel (length, 20 cm, diameter, 1.5 cm; eluꢀ
ent, chloroform—methanol (ratio 50 : 1)). The enriched with
one of the diastereomeric products fractions were obtained:
14а : 14b = 16 : 1 and 14a : 14b = 8 : 1.
D
D
C, 65.22; H, 7.92; N, 3.21. C25H36NO5P. Calculated (%):
1
C, 65.03; H, 7.88; N, 3.03. H NMR, δ: 1.08, 1.19, 1.23, 1.25
(all t, 6 H each, 2 Me, POEt, J = 7.0 Hz); 1.15, 1.31 (both s,
9 Н each, 3 Me, But); 1.63, 1.70 (both d, 3 H each, Me, 2JH,P
=
16.7 Hz, 2JH,P = 16.3 Hz); 2.80 (br.s, 1 H, NH); 2.82—2.94 (m,
2 H, Phe); 3.13, 3.53 (both t, 1 H each, Phe, J = 7.1 Hz, J =
6.9 Hz); 3.63—4.11 (all m, 4 H each, 2 OCH2); 7.13—7.18,
7.20—7.33, 7.56—7.58 (all m, 5 H each, arom.). 31P NMR, δ:
25.49, 25.64. 13C NMR, δ: 16.22—16.48 (m, Me, POEt); 21.24
(s, Me); 27.63 (s, CMe3); 41.84, 42.06 (both s, CH2, Phe);
57.45, 57.92 (both d, CH, Phe, 3JC,P = 13.2 Hz, 3JC,P = 16.1 Hz);
59.79, 60.81 (both d, C(1), 1JC,P = 156.7 Hz, 1JC,P = 152.2 Hz);
62.91—63.20 (m, OCH2); 80.78, 80.84 (both s, CMe3); 126.46,
127.19, 127.31, 127.87, 128.01, 128.11, 128.42, 129.86, 137.57,
137.90, 138.67, 140.32 (Carom.); 174.18, 175.36 (both s, C=O,
Phe). IR, ν/cm–1: 1250 (P=О); 1730 (C=O); 3330, 3450 (NH).
tertꢀButyl Nꢀ[1ꢀcyclopropylꢀ1ꢀ(diethoxyphosphoryl)ethyl]alaꢀ
ninate (12) was obtained from cyclopropyl methyl ketone
and tertꢀbutyl Lꢀalaninate, the yield was 80%, Rf 0.44
(CHCl3—MeOH, 10 : 1). Found (%): C, 54.70; H, 9.20; N, 4.03.
C16H32NO5P. Calculated (%): C, 54.96; H, 9.25; N, 4.00.
1H NMR, δ: 0.38—0.50 (m, 4 Н, 2 CH2, cycl.); 0.92, 0.98
1
Diastereomer 14a, [α]23 –44 (CHCl3). H NMR, δ: 1.19,
D
1.27 (both t, 6 H each, 2 Me, POEt); 1.20 (d, 3 Н, Me Ala, J =
7.0 Hz); 1.35 (s, 9 Н, 3 Me, But); 1.94—2.07, 2.50—2.61 (both m,
2 H each, C(2)H2, cycl.); 2.57 (br.s, 1 H, NH); 2.95—3.00 (m,
2 H, C(3)H2, cycl.); 3.22 (q, 1 Н, Ala, J = 7.0 Hz); 3.89—4.19
(m, 4 H, 2 OCH2); 7.18—7.23, 7.46—7.48 (both m, 4 H, arom.).
31P NMR, δ: 23.84. 13C NMR, δ: 16.29, 16.40 (both d, Me,
3
POEt, JC,P = 5.8 Hz); 21.75 (s, Me, Ala); 27.78 (s, CMe3);
3
3
30.23 (d, CH2, cycl., JC,P = 3.7 Hz); 34.10 (d, C(2)H2, cycl.,
2JC,P = 2.2 Hz); 51.76 (d, CH, Ala, JC,P = 11.0 Hz); 62.84,
62.91 (both d, POCH2, 2JC,P = 7.8 Hz); 68.87 (d, C(1), JC,P
3
1
=
2
2
(both d, 3 H each, Me, JH,P = 16.6 Hz, JH,P = 16.3 Hz);
1.05—1.16 (m, 1 Н, cycl.); 1.20, 1.21 (both d, 3 H each, Me,
Ala, J = 7.0 Hz); 1.29—1.33 (m, 6 H, Me, POEt); 1.42 (s, 9 Н,
3 Me, But); 2.01 (br.s, 1 H, NH); 3.74, 3.79 (both q, 1 H each,
Ala, J = 7.0 Hz); 4.09—4.22 (m, 4 H, 2 OCH2). 31P NMR, δ:
161.7 Hz); 80.53 (s, CMe3); 124.70, 125.86, 126.23, 128.31,
140.01, 145.06 (Carom.); 175.98 (C=O, Ala).
1
Diastereomer 14b, [α]23 –19 (CHCl3). H NMR, δ: 1.17,
D
1.28 (both t, 6 H each, 2 Me, POEt, J = 7.0 Hz); 1.22 (d, 3 Н,
Me, Ala, J = 7.2 Hz); 1.36 (s, 9 Н, 3 Me, But); 2.04—2.17,
2.60—2.72 (both m, 2 H each, C(2)H2, cycl.); 2.43 (br.s, 1 H,
NH); 2.95—3.01 (m, 2 H, C(3)H2, cycl.); 3.44 (q, 1 Н, Ala, J =
7.1 Hz); 3.88—4.19 (m, 4 H, 2 OCH2); 7.16—7.24, 7.47, 7.49
(all m, 4 H each, arom.). 31P NMR, δ: 24.07. 13C NMR, δ:
16.25, 16.31 (both d, Me, POEt, 3JC,P = 5.8 Hz); 21.97 (s, Me,
Ala); 27.75 (s, CMe3); 30.15 (d, C(3)H2, cycl., 3JC,P = 3.7 Hz);
27.25, 27.46. 13C NMR, δ: 0.03, 0.69 (both d, CH, cycl., 2JC,P
=
9.40 Hz); 1.42, 1.66 (both s, 2 CH2, cycl.); 14.49, 14.85 (both d,
2
2
CH3, JC,P = 2.7 Hz, JC,P = 2.7 Hz); 16.16—16.79 (m, Me,
POEt); 21.41, 24.94 (both s, Me, Ala); 27.78, 27.80 (both s,
3
3
CMe3); 51.04, 51.32 (both d, CH, Ala, JC,P = 6.7 Hz, JC,P
=
1
5.4 Hz); 54.69 (d, C(1), JC,P = 158.2 Hz); 61.87, 62.00, 62.43,
62.61 (all d, OCH2, JC,P = 6.72 Hz, JC,P = 8.06 Hz, JC,P
2
2
2
2
=
33.27 (d, C(2)H2, cycl., JC,P = 2.9 Hz); 51.92 (d, CH, Ala,
8.06 Hz, 2JC,P = 6.72 Hz); 80.19, 80.29 (both s, CMe3); 176.31,
176.57 (both s, C=O, Ala). IR, ν/cm–1: 1250 (P=О); 1730
(C=O); 3340, 3470 (NH).
tertꢀButyl Nꢀ[1ꢀcyclopropylꢀ1ꢀ(diethoxyphosphoryl)ethyl]ꢀ
phenylalaninate (13) was obtained from cyclopropyl methyl keꢀ
tone and tertꢀbutyl Lꢀphenylalaninate, the yield was 70%, Rf 0.46
3JC,P = 10.2 Hz); 62.48, 63.22 (both d, POCH2, 2JC,P = 7.3 Hz);
1
68.74 (d, C(1), JC,P = 161.7 Hz); 80.46 (s, CMe3);
124.49, 125.73, 126.26, 128.20, 141.08, 144.54 (Carom.); 175.80
(C=O, Ala).
Synthesis of αꢀamino phosphonates 15—17. LꢀAmino acid
(2.2 mmol), molecular sieves 4 Å (500 mg), PctAlCl (0.1 mmol),