Utilization of Fukuyama's sulfonamide protecting group for the synthesis of N-substituted α-amino acids and derivatives

Tetrahedron Letters

Volumn 41, Issue 18, 2000, Pages 3309-3313

  Lin, Xiaodong ^a   Dorr, Hilary ^a   Nuss, John M ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA AMINO ACID; AMINO ACID DERIVATIVE; FUNCTIONAL GROUP; HETEROCYCLIC COMPOUND; PIPERAZINEDIONE; SULFONAMIDE;

ALKYLATION; AMINO ACID SYNTHESIS; ARTICLE; METHODOLOGY; REACTION ANALYSIS;

EID: 0034728958     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(00)00424-X     Document Type: Article

References (18)

1. (a) Fukuyama, T.; Jow, C.-K.; Cheung, M. Tetrahedron Lett. 1995, 36, 6373. Applications to solid phase synthesis were reported as we were preparing this manuscript:
2. (b) Seitz, O. Angew. Chem., Int. Ed. 1998, 37, 3109.
3. (c) Mohamed, N.; Bhatt, U.; Just, G. Tetrahedron Lett. 1998, 39, 8213.
4. (d) Kung, P.-P.; Swayze, E. Tetrahedron Lett. 1999, 40, 5651.
5. (a) Resin bound α-amimo acids were either purchased from NovaBiochem or prepared by the following procedure. To load amino acids on Wang resin: 4 equiv. DIC, 4 equiv. Fmoc-aa-OH, 2 equiv. DMAP, DCM, rt, 45 min and double coupling. To load amino acids on Rink Amide resin: 4 equiv. Fmoc-aa-OH, 4 equiv. HBTU, 4 equiv. HOBT, 8 equiv. DIEA, NMP, rt, 1.5 h.
6. (b) Functionalized side chains were protected by either tBu (Tyr, Ser, Asp) or Boc (Orn, Lys, Trp). Protecting groups were removed simultaneously upon cleaving compounds off the resin.
7. (c) All reactions were run in a vial using 100 mg of resin in 2 mL solvent with constant agitation.
8. Mitsunobu, O. Synthesis 1981, 1.
9. 1H NMR analysis of compounds A and B showed racemization was <5% (within the limits of detection).
10. Other amino acids such as Met, His(Trt), Arg (Tos), Asn (Trt) and Cys (tBu) resulted in complex mixtures, although the desired compounds 6 were observed.
11. 3CN/50°C, Based upon: Maligres, P. E.; See, M. M.; Askin, D.; Reider, P. J. Tetrahedron Lett. 1997, 38, 5253.
12. DKP formation on solid support with different strategies has been reported: (a) Hulme, C.; Peng, J.; Morton, G.; Salvino, J. M.; Herpin, R.; Labaudiniere, R. Tetrahedron Lett. 1998, 39, 7227.
13. (b) Del Fresno, M.; Alsina, J.; Royo, M.; Barany, G. Albericio, F. Tetrahedron Lett. 1998, 39, 2639.
14. (c) Smith, R. A.; Bobko, M. A.; Lee, W. Bioorg. Med. Chem. Lett 1998, 8, 2369.
15. (d) Szardenings, A. K.; Burkoth, T. S. Tetrahedron 1997, 53, 6573.
16. (e) Kowalski, J.; Lipton, M. A. Tetrahedron Lett. 1996, 37, 5839.
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18. 2O), 27.74 (Me of t-Bu).