Studies toward luzopeptins: Assembly of the elusive serine-PCA dipeptide

Journal of Organic Chemistry

Volumn 62, Issue 8, 1997, Pages 2320-2321

  Ciufolini, Marco A ^a   Xi, Ning ^a  

^a RICE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LUZOPEPTIN;

ARTICLE; DRUG SYNTHESIS; IN VITRO STUDY; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0030927251     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9701952     Document Type: Article

References (36)

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2. (b) Tomita, K.; Hoshino, Y.; Sasahira, T.; Kawaguchi, H. J. Antibiot. 1980, 33, 1098.
3. (c) Arnold, E.; Clardy, J. J. Am. Chem. Soc. 1981, 103, 1243.
4. The most active member of the family, luzopeptin A, is reported to be over 100 times more potent than mitomycin C against P388 leukemia (ref 1a,b).
5. (a) Inouye, Y.; Take, Y.; Nakamura, S. J. Antibiot. 1987, 40, 100.
6. (b) Take, Y.; Inouye, Y.; Nakamura, S.; Allaudeen, H. S.; Kubo, A. J. Antibiot. 1989, 44, 107.
7. Luzopeptin C completely suppressed replication of HIV-1 in infected MT-4 cells at around 2.5-5.0 μg/mL without significant cytopathic effects (ref 3).
8. First synthesis of PCA: (a) Hughes, P.; Clardy. J. J. Org. Chem. 1989, 54, 3260. Synthesis and chemistry of PCA: (b) Ciufolini, M. A.; Xi, N. J. Chem. Soc., Chem. Commun. 1994, 1867 and references cited therein. See also: Greek, C.; Bischoff, L.; Genet, J. P. Tetrahedron: Asymmetry 1995, 8, 1989. Recent work on piperazic acids: (c) Schmidt, U.; Braun, C.; Sutoris, H. Synthesis 1996, 223. Synthesis of 3-hydoxy-valines: (d) Ciufolini, M. A.; Swaminathan, S. Tetrahedron Lett. 1989 30, 2037. (e) Shao, H; Goodman, M. J. Org. Chem. 1996, 61, 2582. Synthesis of the quinaldic acid unit: (f) Boger, D. L.; Chen J. H. J. Org. Chem. 1995, 60, 7369. Total synthesis of sandramycin, a congener of 1 lacking the PCA unit: (g) Boger, D. L.; Chen, J.-H. J. Am. Chem. Soc. 1993, 115, 11624. (h) Boger, D. L.; Chen, J.-H.; Saionz K. W. J. Am. Chem. Soc. 1996, 118, 1629. (i) Unnatural analogues of 1: Olsen, R. K.; Apparao, S.; Bhat, K. L. J. Org. Chem. 1986, 51, 3079.
9. First synthesis of PCA: (a) Hughes, P.; Clardy. J. J. Org. Chem. 1989, 54, 3260. Synthesis and chemistry of PCA: (b) Ciufolini, M. A.; Xi, N. J. Chem. Soc., Chem. Commun. 1994, 1867 and references cited therein. See also: Greek, C.; Bischoff, L.; Genet, J. P. Tetrahedron: Asymmetry 1995, 8, 1989. Recent work on piperazic acids: (c) Schmidt, U.; Braun, C.; Sutoris, H. Synthesis 1996, 223. Synthesis of 3-hydoxy-valines: (d) Ciufolini, M. A.; Swaminathan, S. Tetrahedron Lett. 1989 30, 2037. (e) Shao, H; Goodman, M. J. Org. Chem. 1996, 61, 2582. Synthesis of the quinaldic acid unit: (f) Boger, D. L.; Chen J. H. J. Org. Chem. 1995, 60, 7369. Total synthesis of sandramycin, a congener of 1 lacking the PCA unit: (g) Boger, D. L.; Chen, J.-H. J. Am. Chem. Soc. 1993, 115, 11624. (h) Boger, D. L.; Chen, J.-H.; Saionz K. W. J. Am. Chem. Soc. 1996, 118, 1629. (i) Unnatural analogues of 1: Olsen, R. K.; Apparao, S.; Bhat, K. L. J. Org. Chem. 1986, 51, 3079.
10. First synthesis of PCA: (a) Hughes, P.; Clardy. J. J. Org. Chem. 1989, 54, 3260. Synthesis and chemistry of PCA: (b) Ciufolini, M. A.; Xi, N. J. Chem. Soc., Chem. Commun. 1994, 1867 and references cited therein. See also: Greek, C.; Bischoff, L.; Genet, J. P. Tetrahedron: Asymmetry 1995, 8, 1989. Recent work on piperazic acids: (c) Schmidt, U.; Braun, C.; Sutoris, H. Synthesis 1996, 223. Synthesis of 3-hydoxy-valines: (d) Ciufolini, M. A.; Swaminathan, S. Tetrahedron Lett. 1989 30, 2037. (e) Shao, H; Goodman, M. J. Org. Chem. 1996, 61, 2582. Synthesis of the quinaldic acid unit: (f) Boger, D. L.; Chen J. H. J. Org. Chem. 1995, 60, 7369. Total synthesis of sandramycin, a congener of 1 lacking the PCA unit: (g) Boger, D. L.; Chen, J.-H. J. Am. Chem. Soc. 1993, 115, 11624. (h) Boger, D. L.; Chen, J.-H.; Saionz K. W. J. Am. Chem. Soc. 1996, 118, 1629. (i) Unnatural analogues of 1: Olsen, R. K.; Apparao, S.; Bhat, K. L. J. Org. Chem. 1986, 51, 3079.
11. First synthesis of PCA: (a) Hughes, P.; Clardy. J. J. Org. Chem. 1989, 54, 3260. Synthesis and chemistry of PCA: (b) Ciufolini, M. A.; Xi, N. J. Chem. Soc., Chem. Commun. 1994, 1867 and references cited therein. See also: Greek, C.; Bischoff, L.; Genet, J. P. Tetrahedron: Asymmetry 1995, 8, 1989. Recent work on piperazic acids: (c) Schmidt, U.; Braun, C.; Sutoris, H. Synthesis 1996, 223. Synthesis of 3-hydoxy-valines: (d) Ciufolini, M. A.; Swaminathan, S. Tetrahedron Lett. 1989 30, 2037. (e) Shao, H; Goodman, M. J. Org. Chem. 1996, 61, 2582. Synthesis of the quinaldic acid unit: (f) Boger, D. L.; Chen J. H. J. Org. Chem. 1995, 60, 7369. Total synthesis of sandramycin, a congener of 1 lacking the PCA unit: (g) Boger, D. L.; Chen, J.-H. J. Am. Chem. Soc. 1993, 115, 11624. (h) Boger, D. L.; Chen, J.-H.; Saionz K. W. J. Am. Chem. Soc. 1996, 118, 1629. (i) Unnatural analogues of 1: Olsen, R. K.; Apparao, S.; Bhat, K. L. J. Org. Chem. 1986, 51, 3079.
12. First synthesis of PCA: (a) Hughes, P.; Clardy. J. J. Org. Chem. 1989, 54, 3260. Synthesis and chemistry of PCA: (b) Ciufolini, M. A.; Xi, N. J. Chem. Soc., Chem. Commun. 1994, 1867 and references cited therein. See also: Greek, C.; Bischoff, L.; Genet, J. P. Tetrahedron: Asymmetry 1995, 8, 1989. Recent work on piperazic acids: (c) Schmidt, U.; Braun, C.; Sutoris, H. Synthesis 1996, 223. Synthesis of 3-hydoxy-valines: (d) Ciufolini, M. A.; Swaminathan, S. Tetrahedron Lett. 1989 30, 2037. (e) Shao, H; Goodman, M. J. Org. Chem. 1996, 61, 2582. Synthesis of the quinaldic acid unit: (f) Boger, D. L.; Chen J. H. J. Org. Chem. 1995, 60, 7369. Total synthesis of sandramycin, a congener of 1 lacking the PCA unit: (g) Boger, D. L.; Chen, J.-H. J. Am. Chem. Soc. 1993, 115, 11624. (h) Boger, D. L.; Chen, J.-H.; Saionz K. W. J. Am. Chem. Soc. 1996, 118, 1629. (i) Unnatural analogues of 1: Olsen, R. K.; Apparao, S.; Bhat, K. L. J. Org. Chem. 1986, 51, 3079.
13. First synthesis of PCA: (a) Hughes, P.; Clardy. J. J. Org. Chem. 1989, 54, 3260. Synthesis and chemistry of PCA: (b) Ciufolini, M. A.; Xi, N. J. Chem. Soc., Chem. Commun. 1994, 1867 and references cited therein. See also: Greek, C.; Bischoff, L.; Genet, J. P. Tetrahedron: Asymmetry 1995, 8, 1989. Recent work on piperazic acids: (c) Schmidt, U.; Braun, C.; Sutoris, H. Synthesis 1996, 223. Synthesis of 3-hydoxy-valines: (d) Ciufolini, M. A.; Swaminathan, S. Tetrahedron Lett. 1989 30, 2037. (e) Shao, H; Goodman, M. J. Org. Chem. 1996, 61, 2582. Synthesis of the quinaldic acid unit: (f) Boger, D. L.; Chen J. H. J. Org. Chem. 1995, 60, 7369. Total synthesis of sandramycin, a congener of 1 lacking the PCA unit: (g) Boger, D. L.; Chen, J.-H. J. Am. Chem. Soc. 1993, 115, 11624. (h) Boger, D. L.; Chen, J.-H.; Saionz K. W. J. Am. Chem. Soc. 1996, 118, 1629. (i) Unnatural analogues of 1: Olsen, R. K.; Apparao, S.; Bhat, K. L. J. Org. Chem. 1986, 51, 3079.
14. First synthesis of PCA: (a) Hughes, P.; Clardy. J. J. Org. Chem. 1989, 54, 3260. Synthesis and chemistry of PCA: (b) Ciufolini, M. A.; Xi, N. J. Chem. Soc., Chem. Commun. 1994, 1867 and references cited therein. See also: Greek, C.; Bischoff, L.; Genet, J. P. Tetrahedron: Asymmetry 1995, 8, 1989. Recent work on piperazic acids: (c) Schmidt, U.; Braun, C.; Sutoris, H. Synthesis 1996, 223. Synthesis of 3-hydoxy-valines: (d) Ciufolini, M. A.; Swaminathan, S. Tetrahedron Lett. 1989 30, 2037. (e) Shao, H; Goodman, M. J. Org. Chem. 1996, 61, 2582. Synthesis of the quinaldic acid unit: (f) Boger, D. L.; Chen J. H. J. Org. Chem. 1995, 60, 7369. Total synthesis of sandramycin, a congener of 1 lacking the PCA unit: (g) Boger, D. L.; Chen, J.-H. J. Am. Chem. Soc. 1993, 115, 11624. (h) Boger, D. L.; Chen, J.-H.; Saionz K. W. J. Am. Chem. Soc. 1996, 118, 1629. (i) Unnatural analogues of 1: Olsen, R. K.; Apparao, S.; Bhat, K. L. J. Org. Chem. 1986, 51, 3079.
15. First synthesis of PCA: (a) Hughes, P.; Clardy. J. J. Org. Chem. 1989, 54, 3260. Synthesis and chemistry of PCA: (b) Ciufolini, M. A.; Xi, N. J. Chem. Soc., Chem. Commun. 1994, 1867 and references cited therein. See also: Greek, C.; Bischoff, L.; Genet, J. P. Tetrahedron: Asymmetry 1995, 8, 1989. Recent work on piperazic acids: (c) Schmidt, U.; Braun, C.; Sutoris, H. Synthesis 1996, 223. Synthesis of 3-hydoxy-valines: (d) Ciufolini, M. A.; Swaminathan, S. Tetrahedron Lett. 1989 30, 2037. (e) Shao, H; Goodman, M. J. Org. Chem. 1996, 61, 2582. Synthesis of the quinaldic acid unit: (f) Boger, D. L.; Chen J. H. J. Org. Chem. 1995, 60, 7369. Total synthesis of sandramycin, a congener of 1 lacking the PCA unit: (g) Boger, D. L.; Chen, J.-H. J. Am. Chem. Soc. 1993, 115, 11624. (h) Boger, D. L.; Chen, J.-H.; Saionz K. W. J. Am. Chem. Soc. 1996, 118, 1629. (i) Unnatural analogues of 1: Olsen, R. K.; Apparao, S.; Bhat, K. L. J. Org. Chem. 1986, 51, 3079.
16. First synthesis of PCA: (a) Hughes, P.; Clardy. J. J. Org. Chem. 1989, 54, 3260. Synthesis and chemistry of PCA: (b) Ciufolini, M. A.; Xi, N. J. Chem. Soc., Chem. Commun. 1994, 1867 and references cited therein. See also: Greek, C.; Bischoff, L.; Genet, J. P. Tetrahedron: Asymmetry 1995, 8, 1989. Recent work on piperazic acids: (c) Schmidt, U.; Braun, C.; Sutoris, H. Synthesis 1996, 223. Synthesis of 3-hydoxy-valines: (d) Ciufolini, M. A.; Swaminathan, S. Tetrahedron Lett. 1989 30, 2037. (e) Shao, H; Goodman, M. J. Org. Chem. 1996, 61, 2582. Synthesis of the quinaldic acid unit: (f) Boger, D. L.; Chen J. H. J. Org. Chem. 1995, 60, 7369. Total synthesis of sandramycin, a congener of 1 lacking the PCA unit: (g) Boger, D. L.; Chen, J.-H. J. Am. Chem. Soc. 1993, 115, 11624. (h) Boger, D. L.; Chen, J.-H.; Saionz K. W. J. Am. Chem. Soc. 1996, 118, 1629. (i) Unnatural analogues of 1: Olsen, R. K.; Apparao, S.; Bhat, K. L. J. Org. Chem. 1986, 51, 3079.
17. First synthesis of PCA: (a) Hughes, P.; Clardy. J. J. Org. Chem. 1989, 54, 3260. Synthesis and chemistry of PCA: (b) Ciufolini, M. A.; Xi, N. J. Chem. Soc., Chem. Commun. 1994, 1867 and references cited therein. See also: Greek, C.; Bischoff, L.; Genet, J. P. Tetrahedron: Asymmetry 1995, 8, 1989. Recent work on piperazic acids: (c) Schmidt, U.; Braun, C.; Sutoris, H. Synthesis 1996, 223. Synthesis of 3-hydoxy-valines: (d) Ciufolini, M. A.; Swaminathan, S. Tetrahedron Lett. 1989 30, 2037. (e) Shao, H; Goodman, M. J. Org. Chem. 1996, 61, 2582. Synthesis of the quinaldic acid unit: (f) Boger, D. L.; Chen J. H. J. Org. Chem. 1995, 60, 7369. Total synthesis of sandramycin, a congener of 1 lacking the PCA unit: (g) Boger, D. L.; Chen, J.-H. J. Am. Chem. Soc. 1993, 115, 11624. (h) Boger, D. L.; Chen, J.-H.; Saionz K. W. J. Am. Chem. Soc. 1996, 118, 1629. (i) Unnatural analogues of 1: Olsen, R. K.; Apparao, S.; Bhat, K. L. J. Org. Chem. 1986, 51, 3079.
18. Portions of this work dealing with the preparation of hydrazine 8 by the route shown here and the use of our serinyl chlorides (12) for the creation of PCA-serine dipeptides related to 14 were presented at the 210th National Meeting of the American Chemical Society, Chicago, IL, Aug 1995.
19. Cf. (a) Rebert, N. W. Dissertation, Utah State University, Logan, UT, 1987. (b) Schmidt, U.; Riedl, B. Synthesis 1993, 809. (c) Schmidt, U.; Riedl, B. Synthesis 1993, 815.
20. Cf. (a) Rebert, N. W. Dissertation, Utah State University, Logan, UT, 1987. (b) Schmidt, U.; Riedl, B. Synthesis 1993, 809. (c) Schmidt, U.; Riedl, B. Synthesis 1993, 815.
21. Cf. (a) Rebert, N. W. Dissertation, Utah State University, Logan, UT, 1987. (b) Schmidt, U.; Riedl, B. Synthesis 1993, 809. (c) Schmidt, U.; Riedl, B. Synthesis 1993, 815.
22. Brooks, D.; Kellogg, R. P.; Cooper, C. S. J. Org. Chem. 1887, 52, 192.
23. A noteworthy aspect of this sequence is that hydrogenolytic debenzylation of 4 to 5 was best conducted in nonpolar cyclohexane. Polar solvents such as EtOAc favored cyclization of 5 to the lactone. Furthermore, we found that minimization of the number of steps after introduction of the sensitive hydrazine unit (cf. 8 → 9) was crucial for maximum efficiency. Therefore, it was best to advance 3 to 8 prior to the Gennari-Evans-Vederas reaction.
24. (a) Gennari, C.; Colombo, L.; Bertolini, G. J. Am. Chem. Soc. 1986, 108, 6394.
25. (b) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. J. Am. Chem. Soc. 1986, 108, 6395.
26. (c) Trimble, L. A.; Vederas, J. C. J. Am. Chem. Soc. 1986, 108, 6397.
27. See also: (d) Guanti, G.; Banfi, L.; Narisano, E. Tetrahedron 1988, 44, 5553.
28. 2, rt, 96%) followed by hydrogenolysis (99%). The protocol described in the text removes the need for a separate N-BOC formation.
29. Xi, N.; Ciufolini, M. A. Tetrahedron Lett. 1995, 36, 6595.
30. Other coupling methods based on DCC, DCC-HOBt, BOP-Cl, mixed anhydrides, active esters, etc., failed completely to deliver a serinyl derivative of 11. This may be attributed not only to the innate lack of nucleophilicity of the N-2-atom (ref 5b), exacerbated in the present case by the presence of an electron-withdrawing acyl group on N-1, or to steric congestion in its surroundings, but also to the ease of β-elimination of the OH functionality (or a protected variant thereof) in serine derivatives wherein strong activation has been provided to the COOH terminus.
31. 3) nucleophiles promoted β-elimination of the oxygenated functionality in PCA and subsequent decomposition through aromatization to a pyridazine. Reaction with pyrrolidine (ref 12) resulted not only in deacetylation but also in formal substitution of the OH group by pyrrolidine, probably by Michael addition of the amine into an intermediate α,β-unsaturated ester.
32. Ishizuka, T.; Kunieda, T. Tetrahedron Lett. 1987, 28, 4185.
33. 3.
34. For an important literature analogy see: Askin, D.; Verhoeven, T. R.; Liu, T. M.-H.; Shinkai, I. J. Org. Chem. 1991, 56, 4929.
35. + by the β-OH group, an event that would facilitate departure of the oxygen functionality in an elimination reaction.
36. 2O resulted in preferential OH derivatization; moreover, variable amounts of the N-BOC derivative of the N-butylamide were formed. This problem was no longer apparent with acetate 18.