Synthesis, Bioassay and NMR Study of Methyleneoxy Isosters of Oxytocin and Vasopressin

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Title:Synthesis, Bioassay and NMR Study of Methyleneoxy Isosters of Oxytocin and Vasopressin
Creators:
Mařík, Jan
Buděšínský, Miloš
Slaninová, Jiřina
Hlaváček, Jan
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 67, 3, pp. 373-392
Uncontrolled Keywords:Peptides, Solid phase synthesis, Methyleneoxy isosters, <sup>1</sup>H and <sup>13</sup>C NMR spectroscopy, Biological activity, Peptidomimetics

Abstract

Syntheses of pseudodipeptides H-Tyrψ[CH<sub>2</sub>O]Ile-OH and H-Tyrψ[CH<sub>2</sub>O]Phe-OH were carried out using the intramolecular Williamson reaction of <i>O</i>-benzyltyrosinol with ethyl chloroacetate followed by N-protection and aldol reaction of the corresponding morpholin-3-one in position C<sub>2</sub> with butanone or benzaldehyde, elimination of the hydroxy group to give derivatives with a double bond either as the <i>E</i>/<i>Z</i> (1 : 1) diastereomeric mixture in the case of the former derivative or as the <i>Z</i>-isomer only in the case of the latter one. Stereoselective hydrogenation and hydrolysis of both the lactams yielded the corresponding pseudodipeptides lacking the carbonyl group as a hydrogen bond donor. The introduction of the pseudodipeptides into positions 2 and 3 of oxytocin and vasopressin caused total absence of all biological activities in the formed analogues. The results of the bioassay and NMR study confirmed the importance of the H-bond between the backbone carbonyl of the Tyr<sup>2</sup> and NH proton of the Asn<sup>5</sup> residues for stabilization of the β-turn in the cyclic hexapeptide part of both the hormones and for their biological activity. <p>

Title:Synthesis, Bioassay and NMR Study of Methyleneoxy Isosters of Oxytocin and Vasopressin
Creators:
Mařík, Jan
Buděšínský, Miloš
Slaninová, Jiřina
Hlaváček, Jan
Uncontrolled Keywords:Peptides, Solid phase synthesis, Methyleneoxy isosters, <sup>1</sup>H and <sup>13</sup>C NMR spectroscopy, Biological activity, Peptidomimetics
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:67
Number:3
Page Range:pp. 373-392
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20020373UNSPECIFIED
ID Code:1929
Item Type:Article
Deposited On:06 Feb 2009 17:14
Last Modified:06 Feb 2009 16:14

Citation

Mařík, Jan; Buděšínský, Miloš; Slaninová, Jiřina; Hlaváček, Jan (2002) Synthesis, Bioassay and NMR Study of Methyleneoxy Isosters of Oxytocin and Vasopressin. Collection of Czechoslovak Chemical Communications, 67 (3). pp. 373-392. ISSN 0010-0765

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