Oxytocin synthesis

Oxytocin [50-56-6] M 1007.2, m dec on heating, [a] -26.2"(c 0.53, N AcOH). A cyclic nonapeptide which was purified by countercurrent distribution between solvent and buffer. It is soluble in H2O, rt-BuOH and isoBuOH. [Bodanszky and du Vigneaud J Am Chem Soc 81 2504 1959 Cash et al. J Med Pharm Chem 5 413 1962 Sakakibara et al. Bull Chem Soc Jpn 38 120 1965 solid phase synthesis Bayer and... 

What protected amino acid would you anchor to the solid support in the first step of a synthesis of oxytocin (see Figure 27.8) by the Merrifield method ... 

Rich, D.H., Gesellchen, P.D., Tong, A., Cheung, A., and Buckner, C.K. (1975) Alkylating derivatives of amino acids and peptides. Synthesis of N-maleoyl amino acids, l-[N-maleoylglycyl-cysteinyl]-oxytocin and l-[N-maleoyl-ll-aminoundecanoyl-cysteinyl]-oxytocin. Effects on vasopressin stimulated water loss from isolated toad bladder. J. Med. Chem. 18,1004-1010. 

KM Sivanandiaih, VV Suresh Babu, SC Shrankarama. Solid-phase synthesis of oxytocin using iodotrichlorosilane as Boc deprotecting reagent. Int J Pept Prot Res 45, 377, 1995. 

K Kuromizu, J Meienhofer. Removal of the JW-benzyloxycarbonyl group from cysteine-containing peptides by catalytic hydrogenolysis in liquid ammonia, exemplified by a synthesis of oxytocin. J Am Chem Soc 96, 4978, 1974. 

M Bodanszky, V duVigneaud. A method of synthesis of long peptide chains using a synthesis of oxytocin as an example. J Am Chem Soc 81, 5688, 1959. 

C Johansson, L Blomberg, W Hlebowicz, H Nicklasson, B Nilsson, L Andersson. Industrial production of an oxytocin antagonist Synthetic approaches to the development of a multi-kilogram scale solution synthesis. (Atosiban) In HLS Maia, ed. Peptides 1994. Proceedings of the 23rd European Peptide Symposium. Escom, Leiden, 1995, pp 34-35. 

Borthwick AD, Davies DE, Exall AM, Hatley RJD, Hughes JA, Irving WR, Livermore DG, Sollis SL, Nerozzi F, Valko KL, Allen MJ, Perren M, Shabbir SS, Woollard PM, Price MA (2006) 2, 5-Diketopiperazines as potent, selective, and orally bioavailable oxytocin antagonists. 3. Synthesis, pharmacokinetics, and in vivo potency. J Med Chem 49(14) 4159-4170... 

Fig. 2 Increased synthesis, content and release of vasopressin (AVP) in the PVN of high-anxiety (HAB) vs low-anxiety (LAB) rats under basal circumstances. Above left in situ hybridization. Above right immunocytochemistry (courtesy of Dr. N. Singewald, University of Innsbruck). Middle and below intra-PVN release of AVP and oxytocin (OXT) measured by in vivo microdialysis under basal conditions and in response to hypertonic stimulation to reveal the releasable neuropeptide pool. p<0.05, p<0.01 vs LAB. (Adapted from Wigger et al. 2004)...

The methods presented in the sections above are all suitable for the synthesis of lanthionines as amino acid derivatives. However, a very important synthetic goal remains the synthesis of lanthionine-containing peptides, for example the synthesis of lantibiotics and other peptide analogues where lanthionine has replaced cystine. In the following Sections some syntheses of lanthionine-containing peptides comprising analogues of cystine peptides, such as enkephalin, somatostatin, and oxytocin are described. 

In the early synthesis of deamino-dicarba-oxytocin, the intermediate Z-Asu(OMe)-OH was used which requires a saponification step prior to cyclizationJ1-2 Subsequently, a synthesis more consistent with the general protection strategies in peptide synthesis was developed with the intermediate Z-Asu(OtBu)-OH.12,24 As outlined in Scheme 9, upon selective deprotection of the side-chain carboxy group of the Asu residue by exposure to TFA, the octapeptide derivative 26 is converted into the 2,4,5-trichlorophenyl ester 27 using the tri-fluoroacetate method.129,20 Hydrogenolytic Na-deprotection of 27 in dilute solution leads to... 

Scheme 9 Synthesis of [Asu -6]-Oxytocin by Cyclization via the Active Ester Method13 ...

Oxytocin Oxytocic (lactation-stimulating) 9 Chemical synthesis... 

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