Formation and isolation of simple, stable, acyclic di- and tripeptide hemiacetals

Tetrahedron Letters

Volumn 37, Issue 15, 1996, Pages 2521-2524

  Miller, John F ^a   Spaltenstein, Andrew ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE; OLIGOPEPTIDE;

ARTICLE; NUCLEAR MAGNETIC RESONANCE; PEPTIDE SYNTHESIS; PROTEIN STRUCTURE; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0029866807     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00385-1     Document Type: Article

References (13)

1. Hurd, C. J. Chem. Ed., 1966,43, 527.
2. a. March, J. Advanced Organic Chemistry, 3rd Ed., Wiley-Interscience, 1985, 790, and references cited therein,
3. b. Erickson, J.L.E.; Campell Jr., C.R. J. Am. Chem. Soc., 1954, 76, 4472.
4. Nahm, S.; Weinreb, S. M. Tetrahedron Lett., 1981, 22, 3815.
5. For example, Cbz-isoleucyl-phenylalaninal 1b, quantitatively gave the corresponding cyclized compound fi upon treatment with a trace amount of p-toluenesulfonic acid and standing in chloroform for 2 hours: (matrix presented) A closely related cyclization of an α-carbethoxy glycinal diethylacetal dipeptide has been reported: DiMaio, J.; Belleau, B. J. Chem. Soc. Perkin Trans. I, 1989, 1687.
6. 2O.
7. 6): 3a: δ 10.78 (br s, 2H, indole NH's), 7.82-6.91 (m, 17H, aromatic CH's, amide NH, carbamate NH), [6.44 (d, J=6.8 Hz) and 6.29 (d, J=7.0 Hz), 1H total, diastereomeric OH's], 4.96 (s, 2H, Cbz methylene), 4.50-4.22 (m, 2H, hemiacetal methine, Trp α-methine), 4.07 (m, 1H, C-teminal Trp α-methine), [3.31 (s) and 3.21 (s), 3H total, diastereomeric methoxys], 3.14-2.70 (m, 4H, Trp methylenes). Analysis: C,H,N
8. 6): 3b: δ 7.67 (m, 1H, amide NH), 7.43-7.06 (m, 11H, aromatic CH's, carbamate NH), [6.43 (d, J=6.2Hz) and 6.34 (d, J=7.0 Hz), 1H total, diastereomeric OH's], 5.02 (s, 2H, Cbz methylene), 4.38 (m, 1H, hemiacetal methine),4.02-3.76 (m, 2H, Ile α-methine, Phe α-methine), [3.25 (s) and 3.24 (s), 3H total, diastereomeric methoxys], 3.02-2.71 (m, 2H, Phe methylene), 1.78-0.55 (m, 9H, Ile aliphatic CH's).
9. 3OD solution was also prepared, concentrated to dryness, and examined by electrospray mass spectrometry. Prominent peaks were observed at m/e=397 (M+H for aldehyde) and m/e=455 (M+Na for trideutero methyl hemiacetal). This result eliminates the possibility that we were simply observing a cluster ion of aldehyde 1b (M+Na+MeOH) resulting from reaction with the carrier solvent (methanol) in the spectrometer.
10. +.
11. Spectral data for this compound was consistent with a commercial sample.
12. 12
13. Spaltenstein, A.; Leban, J.J.; Huang, J.J.; Reinhardt, K.R, Viveros, O.H.; Sigafoos, J.; Crouch, R. Tetrahedron Lett., 1996, 37, 0000.