SCOPUS 정보 검색 플랫폼

Synlett

Volumn , Issue 18, 2008, Pages 2785-2790

2-Iminothiolane as a useful coupling reagent for polyamine solid-phase synthesis

(3) Hahn, Frank a Müllen, Klaus b Schepers, Ute a

a UNIVERSITY OF BONN (Germany)

b MAX PLANCK INSTITUTE FOR POLYMER RESEARCH (Germany)

Author keywords

2 iminothiolane; Chemoselectivity; Conjugation; Polyamines; Solid phase synthesis

Indexed keywords

2 IMINOTHIOLANE; MALEIMIDE DERIVATIVE; POLYAMINE; SPERMINE;

ARTICLE; CHEMICAL REACTION; CONJUGATE; MACROMOLECULE; POLYAMINE SYNTHESIS; PROTECTION; SOLID PHASE SYNTHESIS;

EID: 56849129296 PISSN: 09365214 EISSN: None Source Type: Journal
DOI: 10.1055/s-0028-1083566 Document Type: Article

Times cited : (3)

References (24)

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18
- 56849092450
- +.
- +.

19
- 56849122783
- 2 = 5.6 Hz, 1 H), 2.13 (m, 2 H), 1.17 (t, J = 7.2 Hz).
- 2 = 5.6 Hz, 1 H), 2.13 (m, 2 H), 1.17 (t, J = 7.2 Hz).

20
- 56849115014
- Spectroscopic Data for Compound 9 1H NMR (MeOD, 400 MHz, δ, 3.89 (dd, J1, 9.1 Hz, J2, 2.9 Hz, 1 H, 3.52 (q, J, 7.2 Hz, 2 H, 3.38 (t, J, 7.1 Hz, 2 H, 3.19 (dd, J1, 18.5 Hz, J2, 9.1 Hz, 1 H, 3.03 (t, J, 7.7 Hz, 2 H, 2.97 (dd, J1, 13.4 Hz, J2, 6.8 Hz, 1 H, 2.79 (dd, J1, 13.5 Hz, J2, 7.1 Hz, 1 H, 2.61 (t, J, 7.7 Hz, 2 H, 2.46 (dd, J1, 18.6 Hz, J2, 3.7 Hz, 1 H, 2.08 (tt, J1, 7.1 Hz, J2, 7.1 Hz, 1 H, 2.01 (tt, J1, 7.2 Hz, J2, 7.2 Hz, 1 H, 1.13 t, J, 7.2 Hz, 2 H, ESI-HRMS: m/z calcd for C13H 25N4O2S, 301.1693; found: 301.1686
- +: 301.1693; found: 301.1686.

21
- 56849096133
- Ethylmaleimide, phenylmaleimide, and 3-maleimido-propionic acid were purchased from Sigma-Aldrich. The maleimides from entries 4-6 were prepared by the following procedure: 3-maleimidopropionic acid N-hydroxysuccinimide ester (3 equiv) and DIPEA (1 equiv) were dissolved in DMF, and amine (1 equiv) was added in the same of THF. The suspension was stirred for 8 h and THF was removed in vacuo. The remaining suspension was partitioned between CH 3Cl and H2O, and the organic layer was washed with H 2O (3 x, The organic layer was dried over Na2SO 4, and the product was purified by flash chromatography. The products were isolated in 47, 49, and 35% yield and analyzed by HRMS and 1H NMR spectroscopy. In entry 5, CH2Cl2 was used as solvent instead of THF-DMF and DMAP (1 equiv) was added for additional activation
- 2 was used as solvent instead of THF-DMF and DMAP (1 equiv) was added for additional activation.

22
- 56849115810
- Experimental Procedure Alkoxytrityl resin (100 mg) loaded with tris-Aloc-spermine (0.027 mmol, 1 equiv) were swollen in CH 2Cl2 and a solution of Pd(PPh3)4 (6 mg, 0.005 mmol, 0.2 equiv) and of N,N′-dimethylbarbituric acid (33 mg, 0.214 mmol, 8 equiv) in CH2Cl2 (2 mL) were added. The suspension was agitated for 16 h at 40°C. The resin was alternately washed with a solution of sodium N,N-dimethylaminodithiocarbamate in CH 2Cl2-MeOH (4:1) and MeOH (3 x, THF and MeOH (3 x, and CH2Cl2 (3 x, The resin was swollen in THF (1 mL) for 10 min and 2-iminothiolane (11 mg, 0.081 mmol, 3 equiv, in H2O (200 mL) was added. The suspension was agitated for 2 min, then the respective maleimide (2 equiv) in THF (800 mL) was added, and the suspension was agitated for 1 h. The resin was washed with H2O, THF, MeOH 3 x, and CH 2
- 2O-95% MeCN-0.1% AcOH).

23
- 56849106078
- 14) Characterization of the Products of Entries 1-7 (Table 2) Entry 1: 1H NMR (400 MHz, MeOD, δ, 1.14 (t, J, 7.2 Hz, 3 H, 1.79 (m, 4 H, 2.06 (tt, J1, 7.7 Hz, J 2, 7.3 Hz, 4 H, 2.13 (m, 2 H, 2.47 (dd, J1, 18.5 Hz, J2, 3.9 Hz, 1 H, 2.62 (t, J, 7.7 Hz, 2 H, 2.80 (dt, J, 13.5 Hz, J2, 7.0 Hz, 1 H, 2.98 (dt, J1, 13.6 Hz, J2, 6.8 Hz, 1 H, 3.00-3.15 (m, 10 H, 3.19 (dd, J1, 18.5 Hz, J2, 9.1 Hz, 1 H, 3.40 (t, J, 7.1 Hz, 2 H, 3.53 (q, J, 7.3 Hz, 2 H, 3.90 (dd, J1, 9.1 Hz, J2, 3.8 Hz, 1 H, ESI-HRMS: m/z calcd [M, H, 429.3006; found: 429.3010. Entry 2: 1H NMR (400 MHz, MeOD, δ, 1.79 (br m, 4 H, 1.96-2.14 (m, 6 H, 2.60-2.70 (m, 3 H, 2.86 dt, J1, 13.6 H
- 2+: 791.8509; found: 791.8456.

24
- 56849091941
- A proposed sequence would be: (1) Selective introduction of a protection group at the primary amine; (2) protection of the secondary amines; (3) removal of the protection group on the primary amine; (4) elongation with an S-protected building block; (5) deprotection of the thiol; (6) coupling of the thiol to a maleimide; (7) deprotection of the secondary amine.
- A proposed sequence would be: (1) Selective introduction of a protection group at the primary amine; (2) protection of the secondary amines; (3) removal of the protection group on the primary amine; (4) elongation with an S-protected building block; (5) deprotection of the thiol; (6) coupling of the thiol to a maleimide; (7) deprotection of the secondary amine.

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