104974-44-9Relevant articles and documents
Conformationally constrained deltorphin analogs with 2-aminotetralin-2- carboxylic acid in position 3
Tóth, Géza,Darula, Zsuzsa,Péter, Antal,Fül?p, Ferenc,Tourwé, Dirk,Jaspers, Hendrika,Verheyden, Patricia,B?cskey, Zsolt,Tóth, Zoltán,Borsodi, Anna
, p. 990 - 995 (1997)
Two approaches to the design of very active and highly selective δ opioid peptides were used to obtain new deltorphin analogs with altered hydrophobic and stereoelectronic properties. Deltorphin I and II analogs were synthesized involving the substitution of Ile instead of Val at positions 5 and 6 in the address domain and 2-aminotetralin-2-carboxylic acid (Atc) instead of Phe in the message domain. The peptides were agonists in the subnanomolar range in the MVD assay and in the micromolar or higher range in the GPI assay, showing a very high selectivity for δ receptors. A very similar trend could be observed in radioreceptor binding assays in which selective tritiated opioid ligands were used. (R)- and (S)-Atc-deltorphins exhibited similar K(i) values in the binding assay, with almost complete loss of the stereospecificity of the binding. Conformational studies provided evidence for little disturbance of the backbone conformational equilibrium when Phe3 is replaced by (S)- or (R)-Atc. The use of the Atc constraint gives additional evidence that, during its interaction with the δ receptor, the side chain of residue 3 adopts the trans conformation at χ1.
Candida antarctica Lipase B in a chemoenzymatic route to cyclic α-quaternary α-amino acid enantiomers
Li, Xiang-Guo,Rantapaju, Maria,Kanerva, Liisa T.
, p. 1755 - 1762 (2011/05/06)
Kinetic resolution of three cyclic quaternary ethyl 1-amino-2,3-dihydro-1H- indene-1-carboxylates and both 1- and 2-amino-1,2,3,4-tetrahydronaphthalene analogues have been studied. Interesterification with butyl butanoate and Candida antarctica lipase B accomplished the task. The enantiomers of all 1-amino analogues reacted with excellent enantioselectivity (enantiomeric ratio er greater than 200), whereas the 2-amino analogue was not enantioselective (er = 4). Amino acid enantiomers were finally obtained as their respective hydrochlorides with almost maximum theoretical yields. For the first time, a lipase enzyme was effectively used in the kinetic resolution of cyclic α-quaternary α-amino esters. Copyright
Mitsunobu approach to the synthesis of optically active α,α-disubstituted amino acids
Green, Jonathan E.,Bender, David M.,Jackson, Stona,O'donnell, Martin J.,Mccarthy, James R.
supporting information; experimental part, p. 807 - 810 (2009/08/08)
Chiral tertiary α-hydroxy esters of known stereochemical configuration were transformed to α-azido esters by Mitsunobu reaction with HN3. Optimization of this reaction was shown to proceed at room temperature with high chemical yield using 1,1-(azodicarbonyl)dipiperidine (ADDP) and trimethylphosphine (PMe3). Complete inversion of configuration was observed at the α-carbon. Several α,α- disubstituted amino acids were synthesized in high overall chemical yield and optical purity.
Tritiated deltorphin analogues with high specific radioactivity and high affinity and selectivity for delta opioid receptors
Darula, Zsuzsa,Peter, Antal,Toth, Geza
, p. 817 - 826 (2007/10/03)
New conformationally constrained deltorphin I and II analogues were designed and synthesized, using a more lipophilic amino acid (Ile) instead of Val at positions 5 and 6, and 2-aminotetralin-2-carboxylic acid (Atc) at position 3. Two analogues (Tyr-D-Ala-(S)-Atc-Asp-Ile-Ile-Gly-NH2 and Tyr-D-Ala-(R)-Atc-Glu-Ile-Ile-Gly-NH2) with high potency and selectivity for δ opioid receptors were chosen for tritiation, with 3,5-I2-Tyr1-deltorphin analogues as precursors. Catalytic dehalotritiation of these precursors resulted in tritiated peptides with high specific radioactivity (1.28 TBq/mmol (34.5 Ci/mmol) and 1.33 TBq/mmol (36.0 Ci/mmol), respectively).
