Synthesis of novel Gn-RH analogues using Ugi-4MCR

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 3, 2009, Pages 887-890

  Arabanian, Armin ^a   Mohammadnejad, Mahdieh ^a   Balalaie, Saeed ^a   Gross, Jürgen H ^b  

^a K N TOOSI UNIVERSITY OF TECHNOLOGY   (Iran)

^b UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

4 MCR Ugi reaction; Gn RH analogues; Ligation; Triptorelin and gonadorelin analogues

Indexed keywords

ALDEHYDE; CYANIDE; GONADORELIN; GONADORELIN DERIVATIVE; TRIPTORELIN;

ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; SYNTHESIS;

ALDEHYDES; AMINO ACID SEQUENCE; ANIMALS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYANIDES; DRUG DESIGN; GONADOTROPIN-RELEASING HORMONE; HUMANS; MOLECULAR SEQUENCE DATA; PEPTIDES; PROTEIN STRUCTURE, TERTIARY; SPECTROMETRY, MASS, MATRIX-ASSISTED LASER DESORPTION-IONIZATION; TEMPERATURE; TRIPTORELIN;

EID: 58549106757     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.11.111     Document Type: Article

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24. 20 Then a solution of Fmoc-A·A-OH (7.5 mmol), TBTU (2.40 g, 7.5 mmol), DIPEA (3.0 ml, 17.5 mmol) in 30 ml DMF was added to the resin-bound free amine and shaken for 1 h at room temperature. After completion of coupling, resin was washed with DMF (4× 20 ml) and DCM (1× 20 ml). The coupling was repeated as the same methods for other amino acids of their sequences. In all cases for the presence or absence of free primary amino groups, Kaiser Test was used. Fmoc determination was done using UV spectroscopy method. After completion of couplings, resin was washed with DMF (4× 20 ml), DCM (1× 20 ml). The produced heptapeptides 2 were cleaved from resin by treatment of TFA (1%) in DCM (275 ml) and neutralization with pyridine (4%) in MeOH (85 ml). The solvent was removed under reduced pressure and precipitated in water. The yields were 90% (A.A. = Gly) and 84% (A.A. = D-Trp).
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26. 2 over Pd/C catalyst. After removal of Pd/C and the solvent, the residue was collected (yield = 99%). The overall yield for the synthesis tripeptide 3 was 41%.
27. + = 1574.75116.