Acidic coupling and aminolytic TFA cleavage approaches in a new synthesis of an L-m-sarcolysin containing antitumor tripeptide ester

Tetrahedron Letters

Volumn 37, Issue 5, 1996, Pages 563-566

  Weisz, Imre ^a   Roboz, John ^a   Bekesi, J George ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CARBON 14; META SARCOLYSIN; PROLYL[3 [BIS(2 CHLOROETHYL)AMINO]PHENYLALANYL]NORVALINE ETHYL ESTER; TRIPEPTIDE; TRITIUM; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; ISOTOPE LABELING; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS;

TRITIUM;

EID: 0030065343     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(95)02261-9     Document Type: Article

References (10)

1. Yagi, M. J.; Bekesi, J. G.; Daniel, M. D.; Holland, J. F.; deBarbieri, A. Cancer Chemother. Pharmacol. 1984, 12, 70.
2. Hansson, J.; Lewensohn, R.; Ringborg, U. Anticancer Res. 1991, 11, 1725.
3. Ehrsson, H.; Lewensohn, R.; Wallin, I.; Hellstrom, M.; Merlini, G.; Johansson, N. Cancer Chemother. Pharmacol. 1993, 31, 265.
4. deBarbieri, A. Patent (Offenlegungsschrift) # 2128623, Deutsches Patentamt, June 9, 1973.
5. Jones, J. The Chemical Synthesis of Peptides, Claredon Press, Oxford, 1991, p. 42.
6. Muller, E. Methoden der Organischen Chemie (Houben-Weyl), Band XV (Synthese von Peptiden), Teil II, G. Thieme Verlag, Stuttgart, 1974, p. 355.
7. ibid, Teil I, p. 171.
8. The key intermediate, L-m-sarcolysin, L-3-[bis(2-chloroethyl)amino]-L-phenlylalanine, 1, was prepared by converting commercially available 3-nitro-L-tyrosine after esterification and N-acetylation to its phenyltetrazole-ether. The catalytic reduction of this compound led to L-N-acetyl-3-aminophenyl-alanine methyl ester which was next hydroxyethylated and converted into the N-. mustard with mesyl chloride and LiCl; m-sarcolysin was obtained by hydrolysis of the protecting groups.
9. Weisz, I.; Otvos, L.; Arch. Pharm. (Weinheim, Germany), 1985, 318, 766
10. Carpino, L.; Cohen, B.; Stephens, K.; Sadat-Aalae, Y.; Tien, J.; Langridge, D. J. Org. Chem. 1986, 51, 3732.