Synthèse de la Phé²‐oxytocine

Abstract

Rac. 2-dehydro-emetine (XV) and rac. 2-dehydro-isoemetine (XVI) have been synthcsizcd in fivc steps and in good yicld from 2-oxo-3-ethyl-9,10-dimethoxy-l, 2,3, 4,6, . Homologues and analogues of XV and XVI with other substituents have been obtained in the same way.Rac. 2-dchydro-emetine (XV) and its analogucs with other substituents in the isoquinoliiie part exhibit high activity in infections caused by Entanaoeba histolytica. The compounds substitutcd in %position with groups other than an ethyl and all dcrivatives of the clehydro-isometine series show little or no activity. Chemischc Forschungsabtcilung dcr F. HOFFMAXX-LA ROCHE & Co. AG., Basel 86. Synthkse de la PhC2-oxytocine l ) par P.-A. Jaquenoud ct R. A. Boissonnas (12 I11 59)Nous avons dCcrit dans des travaux prCcCdents la synthkse z, 3, 4, et les propriCtCs biologiques4) 5, de diffCrents analogues de l'oxytocine, dans lesquels ou bien l'isoleucine en position 3 Ctait rcmplacCe par la leucine, la valine ou la phknylalanine, ou bien l'asparagine en position 5 par la glutamine.Dam lc prCsent travail, nous rapportons la synthhse d'un autre analogue de l'oxytocine, dans lequel l a tyrosine, en position 2, a CtC remplacCe par la phknylalanine. Cette PhC2-oxytocine (VII) ne posskde donc pas l'hydroxyle phholique present dans l'oxytocine. L'Ctude biologique de cet analogue doit permettre de faire ressortir l'influence de cette fonction hydroxylique sur les diffdrentes activitCs biologiques caractkristiques de l'osytocine.Le schema de synthkse que nous avons utilisC est bask sur le principe que nous avons suivi dans nos travaux prCc6dents2) 3, 6, (voir schCma de synthcse) 7). l) Nous adoptons pour la designation des analogues dc l'oxytocine la nomenclature cEjk utilis6e pr6c6demment dans ce journal pour les analogues dc I'hypertensine par K. SCHWYZER e t coll. (Helv. 40, 614 (1957) ; 41, 1273, 1287 (1958), nomenclature dans laquelle le corps de base e i t pr$c6d6 du I~O T T~ d c l'acide amin6 introduit i la place d'un acide amind d u corps de base avec, en indice, la position, c o m p t k depuis I'extrCmitC N-terminale de la chaine, oh a eu lieu la substitution.

What Amino Acid Properties Affect Protein Evolution?

“…There are two lines of evidence that aromaticity is important. First, it has been experimentally shown that the replacement of tyrosine by phenylalanine (both having an aromatic ring on the side chain) at position 2 of oxytocin has little effect on the oxytocic activity of the peptide (Jaquenoud and Boissonnas 1959;Boissonnas and Guttmann 1960), but the replacement by serine (lacking the aromatic ring) reduces the oxytocic activity to an undetectable level . Second, substitution models based on Grantham's distance or Miyata's distance, neither of which takes aromaticity into consideration, invariably overestimate nonsynonymous substitutions involving codons coding for aromatic amino acids (our unpublished results).…”

Biochemistry of the Protein Hormones

“…The Cornell group has synthetized various analogues of oxytocin [Ressler & (31,32,33) and Rudinger et at. (34) have also synthesized analogues of oxytucin.…”

Effect of Tyrosinase Preparations on Oxytocin, Vasopressin and Bradykinin

“…Phenylalanine2-oxytocin, in which the phenolic hydroxyl group of oxytocin has been removed, was prepared independently by Bodansky & du Vigneaud (1959) and Jaquenoud & Boissonnas (1959). Both groups of workers found an oxytocic potency, measured on the isolated rat uterus, of 30 u./mg.…”