Syntheses of both the putative and revised structures of aeruginosin EI461 bearing a new bicyclic α-amino acid

Organic Letters

Volumn 5, Issue 4, 2003, Pages 447-450

  Valls, Nativitat ^a   Vallribera, Mercè ^a   Carmeli, Shmuel ^b   Bonjoch, Josep ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

^b TEL AVIV UNIVERSITY   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

6 HYDROXY 2 CARBOXYOCTAHYDROINDOLE; AERUGINOSIN; ALPHA AMINO ACID; DEXTRO TYROSINE; DIPEPTIDE; EI 461; HYDROXYL GROUP; INDOLE DERIVATIVE; PEPTIDE; PROTEINASE INHIBITOR; TYROSINE DERIVATIVE; UNCLASSIFIED DRUG; AERUGINOSIN EI461; OLIGOPEPTIDE; TYROSINE;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; DRUG STRUCTURE; DRUG SYNTHESIS; CHEMICAL STRUCTURE; CHEMISTRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STEREOISOMERISM; SYNTHESIS;

DIPEPTIDES; MAGNETIC RESONANCE SPECTROSCOPY; MOLECULAR STRUCTURE; OLIGOPEPTIDES; PROTEASE INHIBITORS; STEREOISOMERISM; TYROSINE;

EID: 0038345087     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol0273250     Document Type: Article

References (21)

1. (a) Ishida, K.; Okita, H.; Matsuda, H.; Okino, T.; Murakami, M. Tetrahedron 1999, 55, 10971-10988 and references therein.
2. (b) Banker, R.; Carmeli, S. Tetrahedron 1999, 55, 10835-10844.
3. For the synthesis and reassignment of aeruginosins 298-A and 298-B, see: Valls, N.; López-Canet, M.; Vallribera, M.; Bonjoch, J. Chem. Eur. J. 2001, 7, 3446-3460.
4. Ploutno, A.; Shoshan, M.; Carmeli, S. J. Nat. Prod. 2002, 65, 973-978.
5. For our previous work in the aeruginosin synthesis, see: (a) Valls, N.; López-Canet, M.; Vallribera, M.; Bonjoch, J. J. Am. Chem. Soc. 2000, 122, 11248-11249. (b) ref 2. (c) Valls, N.; Vallribera, M.; López-Canet, M.; Bonjoch, J. J. Org. Chem. 2002, 67, 4945-4950.
6. For our previous work in the aeruginosin synthesis, see: (a) Valls, N.; López-Canet, M.; Vallribera, M.; Bonjoch, J. J. Am. Chem. Soc. 2000, 122, 11248-11249. (b) ref 2. (c) Valls, N.; Vallribera, M.; López-Canet, M.; Bonjoch, J. J. Org. Chem. 2002, 67, 4945-4950.
7. For our previous work in the aeruginosin synthesis, see: (a) Valls, N.; López-Canet, M.; Vallribera, M.; Bonjoch, J. J. Am. Chem. Soc. 2000, 122, 11248-11249. (b) ref 2. (c) Valls, N.; Vallribera, M.; López-Canet, M.; Bonjoch, J. J. Org. Chem. 2002, 67, 4945-4950.
8. For an alternative synthesis of the L-Choi and the aeruginosin 298-A, see: Wipf, P.; Methot, L.-L. Org. Lett. 2000, 2, 4213-4216.
9. 6b (a) Carroll, A. R.; Pierens, G. K.; Fechner, G.; Leone, P. A.; Ngo, A.; Simpson, M.; Hyde, E.; Hooper, J. N. A.; Boström, S.-L.; Musil, D.; Quinn, R. J. J. Am. Chem. Soc. 2002, 124, 13340-13341. (b) Hanessian, S.; Margarita, R.; Hall, A.; Johnstone, S.; Tremblay, M.; Parlanti, L. J. Am. Chem. Soc. 2002, 124, 13342-13343.
10. 6b (a) Carroll, A. R.; Pierens, G. K.; Fechner, G.; Leone, P. A.; Ngo, A.; Simpson, M.; Hyde, E.; Hooper, J. N. A.; Boström, S.-L.; Musil, D.; Quinn, R. J. J. Am. Chem. Soc. 2002, 124, 13340-13341. (b) Hanessian, S.; Margarita, R.; Hall, A.; Johnstone, S.; Tremblay, M.; Parlanti, L. J. Am. Chem. Soc. 2002, 124, 13342-13343.
11. For the first generation synthesis of Choi derivatives, see: Bonjoch, J. ; Catena, J.; Isábal, E.; López-Canet, M.; Valls, N. Tetrahedron: Asymmetry 1996, 7, 1899-1902.
12. 1H NMR spectra, see ref 2.
13. Compound 7 was synthesized from O-methyl-L-tyrosine in three steps (33% yield) following our procedure described in ref 2, but using a 5 N solution of HCl in MeOH in the cyclization step to avoid the formation of minor quantities of the trans isomer.
14. The reason for the moderate yield in the transformation (7 → 8) is the formation of the cyclohexanone i, due to the retro-Michael process of the starting β-amino ketone 7, the product of which suffers hydrogenation in the reaction medium. This unwanted process did not occur during the formation of N-Boc derivative 3 in the endo series.
15. 4 at -78°C gave 9 (72% yield), and its C-6 epimer was also formed in 11%.
16. The preferred conformation of 7 was ascertained by NMR NOESY data and coupling constant analyses, and its twisted conformation (depicted below) was supported by molecular modeling studies (AM1 method). For details of the structure of compound 7, see ref 2.
17. The NOESY spectrum of 2 showed slight differences from the reported data. We went over the ROESY spectrum of the natural product and found that the correlation between H-2(mj) and H-7a(mj) does exist in the spectrum. However, we found some correlations that contradict this correlation: H-2(mj) with H-3proS(mj), H-7a(mj) with H-3proR(mj), and H-7a(mj) with H-3a(mj). No correlation was found between H-2 and H-3proR. Therefore, we assume that the correlation between H-2(mj) and H-7a(mj), which of course was not observed in 2, is due to a small impurity peak located at 4.72 ppm. The notation mj refers to the major rotamer observed; see Figure 3.
18. Marfey, P. Carlsberg Res. Commun. 1984, 49, 591-596.
19. D +5. Since the original sample of the natural product was slightly impure, its optical rotation was again measured in Tel Aviv from a purified aeruginosin EI461 used for Marfey's analysis (See Supporting Information). The sample was still not perfectly pure, and the quantity of material was low, 0.9 mg. The optical rotation measured was -11 (±5) (c 0.0009, MeOH). Despite the remaining difference and considering all experimental data, we concluded that aeruginosin EI461 is levorotatory and that the real value of its optical rotation is that measured from the pure synthetic aeruginosin 2.
20. For the steric effects on the amide isomer equilibrium of prolyl peptides, see: (a) Beausoleil, E.; Lubell, W. D. J. Am. Chem. Soc. 1996, 118, 12092-12098. (b) Halab, L.; Lubell, W. D. J. Am. Chem. Soc. 2002, 124, 2474-2484.
21. For the steric effects on the amide isomer equilibrium of prolyl peptides, see: (a) Beausoleil, E.; Lubell, W. D. J. Am. Chem. Soc. 1996, 118, 12092-12098. (b) Halab, L.; Lubell, W. D. J. Am. Chem. Soc. 2002, 124, 2474-2484.