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Artyushin et al.
at 20 C for 12 h, the course of the reaction being monitored by
TLC. Then the reaction mixture was concentrated to dryness
in vacuo and purified by chromatography on silica gel using the
hexane—acetone gradient solvent system from 10 : 2 to 1 : 1 and
then the 10 : 1 CH2Cl2—methanol mixture (to isolate the target
products).
(both m, 6 H, CH3CH2CH + CH2CHCH3); 3.72 (s, 3 H,
OCH3); 4.25—4.30, 4.59—4.64 (both m, 1 H + 1 H, OCH2);
5.05—5.15 (m, 2 H, CHNH); 5.31 (br.s, 2 H, NCH2C(O)); 6.65
(br.d, 2 H, NH, 3JH,H = 7.7 Hz); 7.84 (s, 1 H, =CH). 13C—{1H}
NMR (CDCl3), : 11.42 (s, CH3CH2); 15.41 (s, CH3CHC2H5);
21.68, 22.55 (both s, CH3, Pri); 24.70 (s, CHC2H5); 24.83
(s, CH2CH); 28.17 (s, CH3, But); 37.75 (s, CH(CH3)2); 41.04
(s, NCH2C(O)); 50.98 (s, CH(NH)C(O)OCH3); 52.39 (s, OCH3);
52.56 (s, OCH2); 57.81 (s, CH(NH)COCH2); 57.85 (s, OC(CH3)3);
125.39 (s, =CH); 142.92 (s, =C—); 155.44 (s, C(O)OBoc); 164.55
(s, C(O)OCH3); 172.11 (s, C(O)OCH2); 172.62 (s, CH2C(O)NH).
IR (thin layer), /cm–1: 793, 1020, 1049, 1158, 1232, 1252, 1367,
1526 (br, C=O); 1699 (br, C=O); 1743 (C=O); 2876, 2963 (CH);
3318 (br, NH).
Pꢀ{[4ꢀ(NꢀtertꢀButoxycarbonylisoleucineꢀOꢀmethyl)ꢀ1Hꢀ1,2,3ꢀ
triazolꢀ1ꢀylmethyl]}ꢀNꢀ(Oꢀmethylleucine)ꢀOꢀethyl phosphonate
(15). Yield 63%, viscous oil. Found (%): C, 51.14; H, 8.38;
N, 11.21. C24H44N5O8P. Calculated (%): C, 51.33; H, 7.90;
N, 12.47. 1H NMR (CDCl3), : 0.86—0.91 (m, 12 H, CH3, Pri +
+ CH3CH2CH + CH3CHC2H5); 0.92, 0.96 (both d, 3 H,
POCH2CH3,3JH,H = 6.6 Hz); 1.26—1.30 (m, 4 H, CH2CH);
1.42, 1.44 (both s, 9 H, CH3CO); 1.51—1.85 (m, 2 H, CH(CH3)2
+ CHC2H5 + CH3CH2); 3.29 (br.d, 1 H, PNH, 2JH,P = 9.2 Hz);
3.74, 3.75 (both s, 3 H, OCH3), 3.90—4.40 (m, 4 H, POCH2 +
+ C(O)OCH2); 4.71, 4.81 (both d, 2 H, PCH2N, 2JH,P = 13.0 Hz);
{[4ꢀ(NꢀAcetylleucineꢀOꢀmethyl)ꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl]acetꢀ
yl}ꢀNꢀ(Oꢀmethylleucine) (20). Yield 81%, viscous oil. Mixture of
isomers. Found (%): C, 54.35; H, 7.24; N, 15.26. C20H33N5O6•
0.1CH2Cl2. Calculated (%): C, 53.90; H, 7.60; N, 15.60. 1H NMR
(CDCl3), : 0.93—0.99 (m, 12 H, CH3, Pri); 1.52—1.69 (m, 6 H,
CH2CH(CH3)2); 2.02 (s, C(O)CH3); 3.75 (s, OCH3); 4.55—4.69
3
5.04 (br.t, 1 H, CH(NH)CH2, JHH = 8.5 Hz); 5.31 (br.s, 1 H,
CH(NH)C(O)OBut); 7.85, 8.00 (both s, 1 H, =CH). 13C—{1H}
NMR (CDCl3), : 11.31 (s, CH3CH2); 15.27, 15.30 (both s,
3
CH3CHC2H5); 16.03 (d, POCH2CH3, JC,P = 6.20 Hz); 21.11,
(m, 2 H, CHNH); 5.11, 5.15 (both d, 2 H, CH2C(O), 2JH,H
=
21.27 (both s, CH3, Pri); 22.47, 22.61 (both s, CHC2H5); 24.75,
24.78 (both s, CH2CH); 28.05 (s, CH3, But); 37.60, 37.76 (both s,
CH, Pri); 42.78, 43.24 (both d, PNHCH, 2JC,P = 5.8 Hz); 47.60,
= 16.7 Hz); 5.30, 5.35 (both d, 2 H, OCH2, 1JH,H = 12.8 Hz);
6.00, 6.75 (both br.s, 1 H + 1 H, NH); 8.05 (s, 1 H, =CH). 13C—{1H}
NMR (CDCl3), : 21.62, 21.65 (both s, CH3, Pri); 22.58, 22.66,
22.81 (all s, CH, Pri); 24.69 (s, CH3C(O)); 40.87 (s, CH2CHNH);
50.85, 51.02 (both s, CHNH); 52.30 (s, OCH3); 52.39 (s, OCH2);
58.07 (s, CH2C(O)); 125.69 (br.s, =CH); 142.86 (br.s, =C—);
164.91 (s, C(O)OCH3); 170.20 (s, C(O)OCH2); 172.76
(s, NHC(O)CH3). IR (KBr), /cm–1: 963, 1053, 1154, 1231,
1372, 1439, 1545, 16581, 1748 (C=O); 2872, 2960 (CH); 3291
(br, NH).
1
47.83 (both d, PCH2N, JC,P = 138.0 Hz); 52.34 (s, OCH3);
57.77 (s, O—C, BOC); 57.81 (s, OCH2); 61.31, 61.44 (both d,
POCH2, 2JC,P = 6.5 Hz); 124.5 (br.s, =CH); 142.43 (br.s, =C);
155.29 (s, C=O, BOC); 171.90 (s, C(O)OCH3), 174,39
(s, C(O)OCH2). 31P—{1H} NMR (CDCl3), : 18.94 (br.s), 19.40
(br.s). IR (thin layer), /cm–1: 778, 968, 1036 (POC); 1155,
1229 (P=O); 1367, 1456, 1505, 1714, 1743 (C=O); 2875, 2933,
2962 (CH); 3276 (br, NH).
Compounds 16 and 18 (general procedure). Trimethylbroꢀ
mosilane (1.5 mmol) was added to a solution of compound 15 or
17 (1 mmol) in anhydrous CH2Cl2 (5 mL). The mixture was
stirred at 20 C for 8 h and allowed to stand at this temperature
for 48 h. The solvent was removed in vacuo, CH3OH (2 mL) was
added to the residue, and the mixture was kept for 2 h. Then all
volatile products were removed in vacuo, and the residue was
dried with a vacuum oil pump over P2O5.
Pꢀ{[4ꢀ(NꢀAcetylleucineꢀOꢀmethyl)ꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl]ꢀ
methyl}ꢀNꢀ(Oꢀmethylleucine)ꢀOꢀethyl phosphonate (17). Yield
56%, viscous oil. Mixture of isomers. Found (%): C, 50.0; H, 7.8;
N, 13.9; P, 6.1. C21H38N5O7P. Calculated (%): C, 50.1; H, 7.6;
1
N, 13.9; P, 6.15. H NMR (CDCl3), : 0.80—0.95 (m, 12 H,
3
CH3, Pri); 1.19, 1.24 (both br.t, 3 H, P—OCH2CH3, JH,H
=
= 8.5 Hz); 1.35—1.75 (m, 8 H, CH2CHNH + CH, Pri + PCH2);
1.85, 1.89, 1.90 (all br.s, 3 H, CH3C(O)N); 3.66, 3.68 (both s,
3 H, OCH3); 3.85—4.15 (m, 4 H, POCH2 + CHNH); 4.65—4.80
(m, 2 H, C(O)OCH2); 6.41—6.49 (m, 2 H, NH); 7.88, 7.95, 8.07
(all br.s, 1 H, =CH). 13C—{1H} NMR (CDCl3), : 15.98
(d, POCH2CH3, 3JC,P = 6.6 Hz); 20.90, 21.28, 21.48, 22.40, 22.52,
22.54, 22.67 (all s, CH3, Pri + CH3C(O)N); 24.13, 24.27, 24.54
(all s, CH, Pri); 40.30, 40.46, 40.60, 40.63 (all s, CH2CHNH);
47.60, 47.87 (both d, P—CH2N, 1JC,P = 137.8 Hz, 1JC,P = 142.5 Hz);
50.88, 50.96, 51.27 (all s, CHNH); 52.04, 52.12, 52.35, 52.51
(all s, OCH3); 57.84 (br.s, OCH2); 61.05, 61.16, 61.44 (all d,
Pꢀ{[4ꢀ(OꢀMethylisoleucine)ꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl]methyl}ꢀ
Nꢀ(Oꢀmethylleucine) phosphonic acid (16). Yield 95%, viscous oil.
Mixture of isomers. Found (%): C, 47.11; H, 7.12. C17H32N5O6P.
Calculated (%): C, 47.11; H, 7.44. 1H NMR (CD3OD), :
0.94—1.03 (m, 12 H, CH3, Pri + CH3CH2CN + CH3CHC2H5);
1.31—1.38, 1.49ꢀ1.54 (both m, 2 H, CH3CH2CH); 1.72—1.85
(m, 3 H, CH2CH(CH3)2); 2.00—2.10 (m, 1 H, CH—C2H5);
2
3.66 (d, 2 H, PCH2N, JH,P = 10.8 Hz); 3.86 (s, 3 H, OCH3);
4.05—4.09 (m, 2 H, C(O)OCH2); 4.82—4.87 (m, 1 H,
CH(NH)CH2); 5.37—5.45 (m, 1 H, CH(NH2)); 8.19, 8.22
(s, 1 H, =CH). 13C—{1H} NMR (CD3OD), : 10.39 (s, CH3CH2);
13.29, 13.64 (both s, CH3CHC2H5); 20.83, 20.96 (both s, CH3,
Pri); 23.95 (s, CHC2H5); 25.07 (s, CH2CH); 36.12, 36.17 (both s,
CH, Pri); 45.58 (d, PCH2N, 1JP,C = 145.8 Hz); 52.08 (s, OCH3);
58.01 (s, OCH2); 125.66, 125.69, 125.76 (all s, =CH); 141.24,
141.27, 141.32 (all s, =C—); 168.00 (s, C(O)OCH3); 169.77
(s, C(O)OCH2). 31P—{1H} NMR (CD3OD), : 12.4 (s), 13.3 (s).
Pꢀ{[4ꢀ(NꢀAcetylleucineꢀOꢀmethyl)ꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl]ꢀ
methyl}ꢀNꢀ(Oꢀmethylleucine) phosphonic acid (18). Yield 100%,
powder. Mixture of isomers. M.p. 80—90 C. Found (%): C, 36.59;
H, 6.04; N, 10.42; P, 4.86. C19H34N5O7P•1.8 HBr. Calculatꢀ
2
POCH2, JC,P = 6.5 Hz); 125.50 (br.s, =CH Hz); 142.0 (br.s,
=C—); 170.03, 170.07 (both s, C(O)OCH2); 172.45, 172.59 (both
s, C(O)OCH3); 174.27, 174.35, 174.67 (all s, C(O)CH3).
31P—{1H} NMR (CDCl3), : 19.1 (br.s), 19.4 (br.s), 19.5 (br.s).
IR (KBr), /cm–1: 964, 1037 (POC); 1154, 1229 (P=O); 1661,
1747 (C=O); 2872, 2959 (CH); 3270 (br, NH).
{[4ꢀ(NꢀtertꢀButoxycarbonylisoleucineꢀOꢀmethyl)ꢀ1Hꢀ1,2,3ꢀ
triazolꢀ1ꢀyl]acetyl}ꢀNꢀ(Oꢀmethylleucine) (19). Yield 66%, visꢀ
cous oil. Mixture of isomers. Found (%): C, 56.70; H, 8.26;
N, 12.89. C23H39N5O7. Calculated (%): C, 55.52; H, 7.90;
N, 14.07. 1H NMR (CDCl3), : 0.84—0.94 (m, 12 H, CH3, Pri +
+ CH3CH2); 1.43 (br.s, 9 H, CH3, But); 1.10—1.40, 1.50—1.70
1
ed (%): C, 36.70; H, 5.80; N, 11.00; P, 4.98. H NMR (D2O),