15. 7. 1968 Specialia 659 to co-amino nitriles needs to be reconsidered. It is widely believed, for example, that ~-amino acids obtained from several types of simulation experiments were formed by the direct hydrolysis of corresponding ~-amino nitriles x°-lz. In these alkaline reactions, any formation of c~-amino nitriles would soon be followed by elimination of hydrogen cyanide. It therefore seems more likely to us that in such experiments most of the ~-amino acids were products of alkaline hydrolysis of the peptides formed by the poly- merization of hydrogen cyanide present either as a starting material or a reaction intermediate3, 4. It has also been proposed 14-~ that the formation of triglycine from amino- acetonitrile (by heating with kaolinite and extracting with water)x, occurred through a prior condensation be- tween amine and nitrile groups yielding polyamidines. Since black solids were also a major product, it again seems more probable to us that the peptides were formed by base-catalyzed polymerization of hydrogen cyanide following decomposition of the starting material. We con- clude, therefore, that in the reducing and basic environ- ment of primitive Earth, ~-amino nitriles played little or no direct part in the sequence of events leading to the prebiological synthesis of polypeptides and proteins. The main role, instead, was taken by hydrogen cyanide 3,4,18. Zusammen/assung. Neutrale oder alkalische Hydrolyse von Aminoacetonitril gibt mindestens 6 c~-Aminos~uren neben Glycin, welches das einzige Produkt bei saurer ttydrolyse ist. Die anderen a-Aminosiiuren entstehen dutch die Hydrolyse der peptid~hnlichen Polymere, welche dutch die Polymerisierung des aus dem Aminoacetonitril gebildeten Cyanwasserstoffes mit basischen Katalysatoren gebildet werden. Im Zusammenhang mit der chemischen Evolutionstheorie weisen diese Resuttate darauf hin, dass ~-Aminonitrile nut eine kteine oder gar keine direkte Rolle in der Aufeinanderfotge der le.eaktionen gespielt haben, welche zur vorbiologischen Synthese yon Polypeptiden und Proteinen ffihrten. R. E. MOSER and C. N. MATTHEWS Central Research Department, Monsanto Company, Saint Louis (Missouri 63766, USA), 8 April 7968. ls C. N. ~IATTHEWS, H. L. ARONS, A. R. CLAGGETT and R. E. MOSER, Am. chem. Soc., Abstr. 154th Meeting, C265 (1967). Solid Phase Synthesis and Some Pharmacoogical Glumitocin (4-Ser-8-Gln-Oxytocin) was first isolated from Raia clavata z and later identified in 3 additional elasmobranchs, R. batis, R. [ullonica and R. naevus 3. Until very recently the proposed structure had not been con- firmed by laboratory synthesis 4. As part of a continuing investigation on the phylogeny of the neurohypophyseal hormones the synthesis of 4-Ser-8-Gln-Oxytocin was undertaken using the adaptation of the MERRIFI:ELD solid phase method s which has recently been applied toward the synthesis of oxytocin e. The synthetic product has been pharmacologically evaluated by methods previously described 7 and the results obtained are presented in the Table. The required protected nonapeptide amide intermediate was synthesized in a stepwise manner beginning with 5.0 g of t-butyloxycarbonylglycyl resin containing 0.985 mmole of glycine according to the general procedure of MERRI- FIELD 8, using the modifications previously described s with one additional precaution, i.e. the trifluoroacetic acid, dimethylformamide and triethylamine used in the syn- thesis were all fractionally redistilted before use. 8 cycles of deprotection, neutralization and coupling were carried out with appropriate Doe-amino acids 9 producing the protected nonapeptide esterified to the resin. Boc-amino acids with protected side chains were S-Bzl-Cys, O-Bzl-Ser and O-Bzl-Tyr. The final cysteine residue was added as the N-Carbobenzoxy-S-Benzyl (N-Z-S-Bzl) derivative. All coupling reactions to form peptide bonds were medi- ated by dicyclohexylcarbodiimide 10 in methylene chloride except those involving the carboxyl groups of Asn and Gln, which were allowed to react in dimethylformamide (DMF) as their nitrophenyl esters 11. Following the coupling of the final residue, the dried resin weighed 6.057 g. The weight increase of 1.057 g represents the incorporation of 0.81 mmole of protected nonapeptide in the resin. This is 82.2% of the amount expected, based on the original glycine content of 0.985 Properties of 4-Ser-8-Gln-Oxytocin (Glumitocin) i mmole of the esterified resin. Ammonolytic cleavage of the protected nonapeptide resin (2.9 g) was carried out as previously described 8 to give the protected nonapeptide amide Z-Cys(Bzl)-Tyr (Bzl)-Ile-Ser(Bzl)-Asn-Cys(Bzl)-Pro- Gln-Gly(NH2) as a white amorphous powder, weight 464 rag; m.p. 243.5-245 °, [ceil) 2.s -29.0 ° (c, I, dimethyl- formamide). Anal. calcd, for CTeH92Nl~Ol~S~: C, 61.77; H, 6.27; ix]', 11.37. Found: C, 61.97; H, 6.20; ~, 11.28. The yield of the protected nonapeptide amide from the cleavage was 82% of the amount expected based on the increase in weight of the resin. The overall yield based on the amount of glycine originally esterified to the resin x This work was supported in part by a grant from the Medical Research Council of Canada, Banting Research Foundation, Na- tional Science Foundation Grant No. GB 4932X and a General Research Support Grant from the National institutes of Health. 1¢.. ACHER, J. CltAUVET, M. T. CItAUVETand D. CREP¥, Biochim. biophys. Acta 107, 393 (1965). s R. ACHER, Angew. Chem. 5, 798 (1966). While this work was in progress a report on the synthesis of glumitocin by classical methods of peptide synthesis was published : E. KLIECER, Experientia 15, 13 (1968). b R. B. MERRIFIELD, J. Am. chem. Soc. 85, 2149 (1963); Science 150, 178 (1965). s M. MANNING,J. Am. chem. Soc. 90, 1348 (1968). 7 W. H. SAWYER,Gen. eomp. Endocr. 5, 427 (1965}. - W. H. SAWYER, The Pituitary Gland (Eds. G. HARRIS and B. DONOVAN; Butter- worths, London 1966), Vol. 3, p. 288. s R. B. lXIER~IFmLD,Biochemistry 3, 1385 (1954). -G. R. MARSIIALL and R. B. MERRXFIELD, Biochemistry 4, 2394 (1965). 9 The abbreviations used for amino acids and protecting groups are those recommended by the IUPAC-IUB Commission on Bio- chemical Nomenclature, J. biol. Chem. 241, 2491 (1965); Bio- chemistry 5, 1445, 2485 (1966). 10 j . C. SHEEnAN and G. P. HEss, J. Am. chem. Soc. 77, 1067 (1955). 11 M. BODANSZKY and V. DU VmNEAOO, J. Am. chem. Soc. 81, 5688 (1959).