Info

Conclusion b-Amino acids have been found within secondary and primary metabolism of all kingdoms. Although quantitative ranking is tricky, at this point bacteria seem to be the most active ''b-amino acid chemists'', followed by fungi, plants, and animals; we exclude protists from this grading list as a consequence of their lower examination status.

A natural b counterpart has not yet been obtained for every proteinogenic a-amino acid (Table 1.5.1). b-Ala 1 and (R)- or (S)-b-Aib 2 seem to be present in all kingdoms, with no obvious preferences. Selected b-amino acids, for example b-Lys 4, have been found only within one kingdom (i.e. bacteria), although they might be quite common there. Accordingly, the various natural products that contain b-Lys substructures have been isolated exclusively from bacteria. On the other hand, alkaloids and peptides linked to b-Phe 8 have been obtained from bacteria, plants, and fungi, whereas the free b-amino acid b-Phe 8 has not yet been isolated from natural sources.

It is apparent that most known natural b-amino acids have not yet been isolated in form of the free b-amino acid, but obtained only as substructures of alkaloids, peptides, and depsipeptides. Certainly, this general trend does not automatically prove a general preference of b-amino acid substructures with regard to free b-amino acids within natural products.

Rather up-to-date isolation methodology might play a role here, because it results in general discrimination of small molecular weight, polar metabolites. Small, polar compounds, for example free b-amino acids, typically have non-characteristic UV-visible spectra and masses which are often too small for the LC-ESI-MS range commonly scanned; they also elute ''with the solvent front'' under standard reversed-phase chromatography conditions. Finally, they might have only a weak or no biological activity in a bioassay set up ''randomly'' with regard to their ''original'' biological function.

Not only within industrial natural-product research, LC-ESI-MS-guided, UV-guided, and activity-guided searching for substances is performed out in the middle polarity range under more or less standardized conditions. Certainly this established methodology leads to the desired higher output of new natural products. A cut within the structural [140] and sensitivity windows seems to be unavoidable, however, and we are blinded by these methods for polar compounds with low molecular weights.

Several natural alkaloids, peptides, and depsipeptides related to b-amino acids are active antibacterial, antifungal, or cytotoxic compounds (Tables 1.5.1 and 1.5.2). Accordingly, b-amino acids already have implications within medicinal chemistry as lead structures or as analogs of a-amino acids within peptides or peptidomi-metics. Selected examples have been discussed.

Dedication

Dedicated to Professor Wolfgang Steglich on the occasion of his 70th birthday. Acknowledgment

We are grateful to Dr Norbert Arnold and Dr Marc Stadler for many valuable hints and suggestions and to the Alexander von Humboldt-Stiftung for a Feodor-Lynen-Stipendium to F.v.N. and P.S.

References

1 For previous reviews dealing with natural b-amino acids see: (a) O. W. Griffith, Ann. Rev. Biochem. 1986, 55, 855-878; (b) C. N. C. Drey, Beta and Higher Homologous Amino Acids in Chemistry and Biochemistry of the Amino Acids, G. C. Barrett, ed.,

Chapman and Hall, London, 1985, pp. 25-54; (c) C. N. C. Drey, The Chemistry and Biochemisty of ß-Amino Acids, G. Weinstein, ed., The Chemistry and Biochemistry of the Amino Acids, Dekker, New York, 1976, 4, 241-299.

2 P. A. Frey, C. H. Chang, Amino-mutases in Chemistry and Biochemistry of B12, R. Banerjee, ed., Wiley, New York, 1999, pp. 835-857. For further references on Frey's work see biosynthesis section.

3 J. J. Baker, T. C. Stadtman, Amino-mutases in Bi2 : Biochemistry and Medicine, Vol. 2, D. Dolphin, ed., Wiley, New York, 1982, pp. 203-232.

4 (a) P. E. Fleming, U. Mocek, H. G. Floss, J. Am. Chem. Soc. 1993, 115, 805-807; (b) K. D. Walker, H. G. Floss, J. Am. Chem. Soc. 1998, 120, 5333-5334.

5 P. Spiteller, M. Rüth, F. von Nussbaum, W. Steglich, Angew. Chem. Int. Ed. 2000, 39, 2754-2756.

6 J. Tamariz, Biological Activity of ß-Amino Acids and ß-Lactams in Enantioselective Synthesis ofß-Amino Acids, E. Juaristi, ed., Wiley-VCH, New York, 1997, 45-66.

7 A. D. Hanson, B. Rathinasabapathi, J. Rivoia, M. Burnet, M. O. Dillon, D. A. Gage, Proc. Natl. Acad. Sci. USA 1994, 91, 306-310.

8 Marine methanogenic archaebacteria respond to osmotic stress by accumulating Ne-acetyl-ß-lysine and ß-Glu as metabolism ''complatible solutes'': (a) K. R. Sowers, D. E. Robertson, D. Noll, R. P. Gunsalus, M. F. Roberts, Proc. Natl. Acad. Sci. USA 1990, 87, 9083-9087; (b) D. E. Robertson, D. Noll, M. F. Roberts, J. Biol. Chem. 1992, 267, 14893-14901.

9 ß-Glu is a major soluble component of Methanococcus thermolithotrophicus.

(a) E. E. Robertson, S. Lesage, M. F. Roberts, Biochim. Biophys. Acta 1989, 992, 320-326; (b) D. D. Martin, R. A. Ciulla, P. M. Robinson, M. F. Roberts, Biochim. Biophys. Acta 2000, 1524, 1-10.

10 (a) K. Ziegelbauer, P. Babczinski, W. Schönfeld, Antimicrob. Agents Chemother. 1998, 42, 2197-2205;

KuNiscH, M. Matzke, H.-C. Milit-zer, K.-M. Möhrs, A. Schmidt, W. Schönfeld, Poster, ICAAC, San Diego, 2002; (c) J. Mittendorf, J. Benet-Buchholz, P. Fey, K.-H. Möhrs, Synthesis 2003, 136-140.

11 (a) G. Cardillo, C. Tomasini, Chem. Soc. Rev. 1996, 117-128; (b) N. Fusetani, S. Matsunaga, Chem. Rev. 1993, 93, 1793-1806; (c) C. E. Baliard, B. Wang, Curr. Med. Chem. 2002, 9, 471-498.

12 (a) N. Sewald, Bioorganic Chemistry, U. Diedrichsen, T. K. Lindhorst, B. Westermann, L. A. Wessjohann, eds., Wiley-VCH, Weinheim, 1999; (b) M. North, J. Peptide Sci. 2000, 6, 3001-3313.

13 E. Abderhalden, R. Fleischmann, Fermentforschung 1928, 10, 173.

14 A selection of recent activity: (a) S. Reinelt, M. Marti, S. DEdier, T. Reitinger, G. Folkers, J. A. Lopez de Castros, D. Rognan, J. Biol. Chem. 2001, 276, 24525-24530;

(b) R. A. Lew, E. Boulos, K. M. Steward, P. Perlmutter, M. F. Harte, S. Bond, M.-I. Aguiiar, A. I. Smith, J. Peptide Sci. 2000, 6, 440-445.

15 Furthermore, the incorporation of d-amino acids or other unusual (often hydroxylated) amino acids, the N-methylation of amide functionalities or the usage of cyclic peptides and depsipeptides limits these problems to a certain extent.

16 (a) R. P. Cheng, S. H. Gellman, W. F. DeGrado, Chem. Rev. 2001, 101, 3219-3232; (b) K. Gademann, T. Hintermann, J. V. Schreiber, Curr. Med. Chem. 1999, 6, 905-925; (c) S. H. Gellman, Acc. Chem. Res. 1998, 31, 173-180; (d) D. Seebach, J. L. Matthews, Chem. Commun. 1997, 2015-2022.

S. R. Durell, S. H. Gellman, J. Am. Chem. Soc. 1999, 121, 2309-2310; (b) D. H. Appella, L. A. Christian-son, D. A. Klein, D. R. Powell, X. Huang, J. J. Barchi Jr, S. H. Gellman, Nature 1997, 387, 381-384.

18 (a) D. Seebach, K. Gademann, J. V. Schreiber, J. L. Matthews, T.

Hinteemann, B. Jaun, L. Oberer, U. Hümmel, H. Widmer, Hdv. Chim. Acta 1997, 80, 2033-2038; (b) M. Rueping, J. V. Schreiber, G. Lelais,

B. Jaun, D. Seebach, Helv. Chim. Acta 2002, 85, 2577-2593.

19 (a) J. M. FERNANDEZ-SANTiN, J. AYMAMi, A. RüDRiGUEZ-GAlAN, S. MuNüz-Gueeea, J. A. Subirana, Nature (London) 1984, 311, 53;

(b) A. M. De Ilarduya, C. AlemaN, M. GARCiA-AlVAREZ, F. Lüpez-Carrasquerü, S. MuNüz-Guerra, Macromolecules 1999, 32, 3257.

20 (a) M. Liu, M. P. Sibi, Tetrahedron, 2002, 58, 7991-8035; (b) S. Abele, D. Seebach, Eur.J. Org. Chem. 2000, 115; (c) Enantioselective Synthesis of ß-Amino Acids, E. Juaristi, ed., Wiley-VCH, New York, 1997; (d) D. C. Cüle, Tetrahedron 1994, 50, 9517-9582;

(e) E. Juaristi, D. Quintana, J. Escalante, Aldrichim. Acta 1994, 27, 3-11.

21 Recent examples: (a) I. Karle, H. N. Güpi, P. Balaram, Proc. Natl. Acad. Sci. USA 2002, 99, 5160-5164; (b) R. Günther, H.-J. Hüfmann, J. Am. Chem. Soc. 2001, 123, 247-255.

22 (a) E. Juaristi, H. Lopez-Ruiz, Curr. Med. Chem. 1999, 6, 983-1004; (b) A. F. Abdel-Magid, J. H. Cohen, C. A. Marynoff, Curr. Med. Chem. 1999, 6, 955-970.

23 (a) Dictionary of Natural Products, Chapman and Hall/CRC, CD-ROM, 1982-2003; (b) Rompp Encyclopedia -Natural Products, W. Steglich, B. Fugmann, S. Lang-Fugmann, eds., Georg Thieme, Stuttgart, 2000.

24 T. Hintermann, D. Seebach, Chimica 1997, 51, 244-247.

25 J. V. Schreiber, J. Frackenpohl, F. Müser, T. Fleischmann, H.-P. Kühler, D. Seebach, ChemBioChem. 2002, 3, 424-432.

D. Hoyer, D. Seebach, Angew. Chem. Int. Ed. 1999, 38, 1223-1226; (b) D. Seebach, M. Rueping, P. I. Arvids-son, T. Kimmerlin, P. Micuch,

28 (3S,4S,5E,7E)-3-Amino-4-hydroxy-6-methyl-8-(4-bromophenyl)-octa-5,7-dienoic acid [Aboa i Br-Ahmp, Br-Apoa]. (2S,3S,8S,9S)-3-Amino-9-methoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dienoic acid (Adda). 3-Amino-2,4-dimethylpentanoic acid (Admpa). (2S,3R,5S)-3-amino-2,5,9-trihydroxy-10-phenyldecanoic acid (Ahda). ß-Aminoisobutyric acid (ß-AiB). (3S,4S,5E,7E )-3-Amino-4-hydroxy-6-methyl-8-phenylocta-5,7-dienoic acid [Ahmp (Faulkner) or Apoa (Fusetani)]. (2S,3R,5R)-3-Amino-2,5-dihydroxy-8-phenyloctanoic acid (Ahoa). 3-Aminopentanoic acid (Apa 0 ß-Apa). (2R,3R)-3-Amino-2-methylbutanoic acid (Amba). 3-Amino-2-methylhexanoic acid (Amha). 3-Amino-2-methyl-7-octynoic acid (Amoa, Amoya). 3-Amino-7-octynoic acid (Aoya). (2S,3R)-3-Amino-2-methylpentanoic acid (Map).

29 http://www.ncbi.nlm.nih.gov/Taxonomy/ tax.html

30 T. P. Begley, C. Kinsiand, E. Strauss, Vitam. Horm., 2001, 61, 157-171.

31 A. A. Boldyrev, Int. J. Biochem. 1990, 22, 129-132.

32 (a) M. S. C. Pedras, L. Irina Zaharia, D. E. Ward, Phytochemistry 2002, 59, 579-596; (b) Y. Kodaira, Agr. Biol. Chem. 1961, 25, 261-262; (c) H. S. Kim, M. H. Jung, S. Ahn, C. W. Lee, S. N. kim, J. H. ok, J. Antibiot. 2002, 55, 598-601.

33 A. Farooq, S. Tahara, Curr. Top. Phytochem. 2000, 3, 95-111.

34 S. C. Pedras, K. C. Smith, Phytochemistry 1997, 46, 833-837.

35 J. C. Frisvad, U. Thrane, O. Fil-tenborg, Role and Use of Secondary Metabolites in Fungal Taxonomy, in Chemical Fungal Taxonomy, J. C. Frisvad, P. D. Bridge, D. K. Arora, eds., Marcel Dekker, New York, 1998, pp. 289-313.

36 R. E. Moore, G. Bartolini, J. Am. Chem. Soc. 1981, 103, 2491-2494.

37 N. Sitachitta, R. T. Williamson, W. H. Gerwick, J. Nat. Prod. 2000, 63, 197-200.

38 (a) R. G. Keil, E. Tsamakis, J. C. Giddings, J. I. Hedges, Geochim. Cosmochim. Acta 1998, 62, 1347-1364; (b) H. Kawahata, T. Ishizuka, Oceanol. Acta 1993, 16, 373-379.

39 Isolation: (a) K. Hamano, M. Kino-shita, K. Furuya, M. Miyamoto, Y. Takamutsu, A. Hemmi, K. Tanzawa, J. Antibiot. 1992, 45, 899905. Structure elucidiation: (b) K. Hamano, M. Konoshita, K. Tanzawa, K. Yoda, Y. Ohki, T. Nakamura, T. Kinoshita, J. Antibiot. 1992, 45, 906-913.

40 (a) C. Rossi, L. Tuttobello, M. Ricci, C. G. Casinovi, L. Radics, J. Antibiot. 1987, 40, 130-133; (b) G. A. Strobel, W. M. Hess, Chem. Biol. 1997, 4, 529536.

41 T. M. Soniat, M. L. Koenig, J. Shellfish Res. 1982, 2, 25-28.

42 Isolation of arenastatin A (crypto-phycin-24) from a marine sponge (Dysidea arenaria): (a) M. Kobayashi, S. Aoki, N. Ohyabu, M. Kurosu, W. Wang, I. Kitagawa, Tetrahedron Lett. 1994, 35, 7969-7972. Synthesis: (b) M. Kobayashi, M. Kurosu, W. Wang, I. Kitagawa, Chem. Pharm. Bull. 1994, 42, 2394-2396; (c) M.-J. Eggen, S. K. Nair, G. I. Georg, Org. Lett. 2001, 3, 1813-1815.

43 M. C. Roy, I. I. Ohtani, T. Ichiba, J. Tanaka, R. Satari, T. Higa, Tetrahedron 2000, 56, 9079-9092.

44 Compare cited literature: M. Doi, T. Ishida, M. Kobayashi, Y. Katasuya, Y. Mezaki, M. Sasaki, A. Terashima, T. Taniguchi, C. Tanaka, Biopolymers 2000, 54, 27-34.

45 (a) H. Rembold, Y. Umebachi, Progress in Tryptophan and Serotonin Research 1984, 743-746; Chem. Abstr. 1984, 101, 87654s; (b) P. B. Koch, B. Behnecke, M. Weigmann-Lenz, R. H. Ffrench-Constant, Pigment Cell Research, Suppl. 2000, 8, 54-58.

46 Y. Guillou, Y. Robin, J. Biol. Chem. 1973, 248, 5668-5672.

47 (a) R. E. Schwartz, C. F. Hirsch, D. F. Sesin, J. E. Flor, M. Chartrain, R. E. Fromtling, G. H. Harris, M. J. Salvatore, J. M. Liesch, K. J. Yudin, J. Ind. Microbiol. 1990, 5, 113-123; (b)

G. V. Subbaraju, T. Galakoti, G. M. L. Patterson, R. E. Moore, J. Nat. Prod. 1997, 60, 302-305. Structure: (c) T. Golakoti, J. Ogino, C. E. Heltzel, T. L. Husebo, C. M. Jensen, L. K. Larsen, G. M. L. Patterson, R. E. Moore, S. L. Mooberry, T. H. Corbett, F. A. Valeriote, J. Am. Chem. Soc. 1995, 117, 12030-12049. Synthesis: (d) J. D. White, J. Hong, L. A. Robarge, J. Org. Chem. 1999, 64, 6206-6216.

48 S. A. Currie, T. W. Miller, J. P. Springer, M. E. Valiant, S. B. Zimmerman, S. M. Del Vai (Merck and Co. Inc.), EP 332248, 1989.

49 N. Sato, M. Furuya, Phytochemistry 1984, 23, 1625-1627.

50 Isolation of DGTA [1,2-diacylglyceryl-O-2 '-(hydroxymethyl)-N, N, N,N-trimethyl-b-Ala] from marine algae, such as green algae and brown algae:

(a) V. E. Vaskovsky, S. V. Khotimchenko, B. Xia, L. Hefang, Phytochemistry 1996, 42, 1347-1356;

(b) M. Kato, M. Sakai, K. Adachi, H. Ikemoto, H. Sano, Phytochemistry 1996, 42, 1341-1345.

R. W. Andreotti, L. Lond, T. Hasselstrom, J. Agr. Food Chem. 1967, 15, 1040-1043.

52 T. Sugawara, A. Tanaka, K. Tanaka, K. Nagai, K. Suzuki, T. Suzuki, J. Antibiot. 1998, 51, 435-438.

53 Distribution of DGTA in non-vascular green plants, such as mosses (Bryop-sida) and green algae (Chlorophyceae): N. Sato, M. Furuya, Plant Sci. 1985, 38, 81-85.

54 J. M. Poston, J. Biol. Chem. 1980, 255, 10067-10072. For further references see biosynthesis section.

55 Sperabillin C has a <5-OH-b-D-Lys substructure: T. Hida, S. Tsubotani, Y. Funabashi, H. Ono, S. Harada, Setsuo, Bull. Chem. Soc. Jpn. 1993, 66, 863-869.

56 K. Ohba, H. Nakayama, K. Furihata, K. Furihata, A. Shimazu, H. Seto, N. (Stake, Y. Zhao-Zhong, X. Li-Sha, X. Wen-Si, J. Antibiot. 1986, 39, 872-875.

57 Lavendothricin is related to the strepthricins. Isolation: N. Dobreva,

B. Vasileva, Farmatsiya (Sofia) 1977, 27, 25-29.

58 (+)-Negamycin contains ¿-OH-jS-d-Lys. Isolation: (a) M. Hamada, T. Takeuchi, S. Kondo, Y. Ikeda, H. Naganawa, K. Maeda, Y. Okami, H. Umezawa, J. Antibiot. 1970, 23, 170171. Structure: (b) S. Kondo, S. Shibahara, S. Takahashi, K. Maeda, H. Umezawa, M. Ohno, J. Am. Chem. Soc. 1971, 93, 6305-6306. For a recent synthesis see: (c) R. P. Jain, R. M. Williams, J. Org. Chem. 2002, 67, 6361-6365.

59 Isolation: (a) R. L. Peck, A. Walti, R. P. Graber, E. Flynn, C. E. Hoffhine Jr, V. Allfrey, K. Folkers, J. Am. Chem. Soc. 1946, 68, 772-774. Biosynthesis: (b) K. J. Martinkus,

C.-H. Tann, S. J. Gould, Tetrahedron 1983, 39, 3493-3505. Review: (c) H. Thrum, Drugs Pharm. Sci. 1984, 22, 367-386.

60 (a) Isolation and structure elucidation: Y. Ikeda, S. Kondo, D. Ikeda, K. Yokose, H. Furutani, T. Ideka, M. Hamada, M. Ishizuka, T. Takeuchi, H. Umezawa, J. Antibiot. 1986, 39, 476-478. Biosynthesis via an i-Lys-2,3-aminomutase: (b) Y. Ikeda, H. Naganawa, S. Kondo, T. Takeuchi, J. Antibiot. 1992, 45, 1919-1924. Synthesis: (d) Y. Ikeda, D. Ikeda, S. Kondo, J. Antibiot. 1992, 45, 16771680.

61 T. Wakamiya, T. Shiba, J. Antibiot. 1974, 27, 900-902.

62 T. Kitagawa, Y. Sawada, T. Miura, T. Ozasa, H. Taniyama, Tetrahedron Lett. 1968, 1, 109-113.

63 J. H. MARTIN, J. P. KIRBY, D. B. Borders, A. A. Fantini, R. T. Testa (American Cyanamide), EP 58838 1983.

64 W. J. McGahren, B. A. Hardy, G. O. Morton, F. M. Lovell, N. A. Perkinson, R. T. Hargreaves, D. B. Borders, G. A. Ellestad, J. Org. Chem. 1981, 46, 792-799.

65 J. C. French, Q. R. Bartz, H. W. Dion, J. Antibiot. 1973, 26, 272-283.

66 M. W. Jackson, R. J. Theriault, A. C. Sinciair, E. E. Fager, J. P.

Karwowski (Abbot Laboratories), DE 3003497.

67 (a) N. Katayama, S. Fukusumi, Y. Funabashi, T. Iwahi, H. Ono, J. Antibiot. 1993, 46, 606-613. Structure:

(b) Y. Funabashi, S. Tsubotani, K. Koyama, N. Katayama, S. Harada, Setsuo Tetrahedron 1993, 49, 13-28;

(c) R. M. Williams, C. Yuan, V. J. Lee, S. Chamberland, J. Antibiot. 1998, 51, 189-201; (d) V. V. Sokolov, S. I. Kozhushkov, S. Nikolskaya, V. N. Belov, M. Es-Sayed, A. de Meijere, Eur. J. Org. Chem. 1998, 777-783. Mode of action: (e) W. S. Champney, J. Pelt, C. L. Tober, Curr. Microbiol. 2001, 43, 340-345. Biology: (f) M. Brands, M. Es-Sayed, D. HAbich, S. Raddatz, J. Krüger, R. Endermann, R. Gahlmann, H.-P. Kroll, F.-U. Geschke, A. de Meijere, V. N. Belov, V. Sokolov, S. Kozhushkov, M. Kordes, (Bayer A.G.), W0-0012484-A1, 2000.

68 Isolation: (a) S. Takeuchi, K. Hirayama, K. Ueda, H. Sakai, H. Yonehara, J. Antibiot. 1958, 11A, 1-5. Biosynthesis: (b) H. Seto, H. Yonehara, J. Antibiot. 1977, 30, 10191021; (c) H. Seto, H. Yonehara, ibid. 1977, 30, 1022-1024.

69 Stereochemistry of LL-BM 547b according to the structurally related viomycins. W. J. McGahren, G. O. Mortam, M. P. Kunstmann, A. G. Ellstad, J. Org. Chem. 1977, 42, 12821286.

70 S. M. Henrichs, R. Cuhel, Appl. Environ. Microbiol. 1985, 50, 543545.

71 jS-Glu is a major constituent of dissolved free amino acids (DFAA) in marine sediments. (a) S. M. Henrichs, J. W. Farrington, Nature 1979, 179, 319-322; (b) D. J. Burdige, C. S. Martens, Biogeochemistry 1989, 8, 1-23; (c) J. C. Colombo, N. Silver-berg, J. N. Gearing, Organic Geochemistry 1998, 29, 933-945.

72 E. Fattorusso, M. Piatelli, Amino Acids from Marine Algae in Marine Natural Products, P. J. Scheuer, eds., Academic Press, New York, 1980, pp. 95-140.

73 (a) F. Itagaki, H. Shigemori, M. ISHIBASHI, T. Nakamura, T. Sasaki, J.-i. Kobayashi, J. Org. Chem. 1992, 57, 5540-5542; (b) J.-i. Kobayashi, R. Itagaki, H. Shigemori, T. Takao, Y. Shimonishi, Tetrahedron 1995, 51, 2525-2532. Synthesis: (c) J. A. Sowinski, P. L. Toogood, Chem. Commun. 1999, 981-982.

74 C. A. Bewley, D. J. Faulkner, J. Org. Chem. 1994, 59, 4849-4852; ibid. 1995, 60, 2644.

75 Theonellamides A-F, isolation:

(a) S. Matsunaga, N. Fusetani, K. Hashimoto, M. Walchli, J. Am. Chem. Soc. 1989, 111, 2585-2588. Theonellamides B, C: (b) S. Matsunaga, N. Fusetani, J. Org. Chem. 1995, 60, 1177-1181. Biological activity: (c) S.-I. Wada, S. Matsunaga, N. Fusetani, S. Watabe, Mar. Biotechnol. 2000, 2, 285-292.

76 E. W. Schmidt, C. A. Bewley, D. J. Faulkner, J. Org. Chem. 1998, 63, 1254-1258.

77 Isolation from a bacterial symbiont (Enterobacter sp.) of a brown planthopper (Nilaparvata lugens): (a) A. Fredenhagen, S. Y. Tamura, P. T. M. Kenny, H. Komura, Y. Naya, K. Nakanishi, K. Nishiyama, M. Sugiura, H. Kita, J. Am. Chem. Soc. 1987, 109, 4409-4411; (b) M. P. Singh, M. J. Mroczenski-Wildey, D. A. Steinberg, R. J. Andersen, W. M. Maiese, M. Greenstein, J. Antibiot.

78 Isolation: (a) J. Needham, M. T. Kelly, M. Ishige, R. J. Andersen, J. Org. Chem. 1994, 59, 2058-2063. Synthesis: (b) S. G. Davies, D. J. Dixon, J. Chem. Soc. Perkin Trans. 1

1998, 17, 2635-2644.

79 (a) H. Yoshioka, K. Nakatsu, M. Sato, T. Tatsuno, Chem. Lett. 1973, 1319-1322; (b) T. Tatsuno, M. Tsukioka, Y. Sakai, Y. Suzuki, Y. Asami, Chem. Pharm. Bull. 1955, 3, 476-477.

80 J. L. Corbin, B. H. Marsh, G. A. Peters, Phytochemistry 1986, 25, 527528.

81 (a) M. Koyama, Y. Obata, Agr. Biol. Chem. 1966, 30, 472-477; (b) M.

Koyama, Y. Obata, Agr. Biol. Chem. 1967, 31, 738-742.

82 (a) S. Kosemura, T. Ogawa, K. Totsuka, Tetrahedron Lett. 1993, 34, 1291-1294; (b) K. K. Schumacher,

D. B. Hauze, J. Jiang, J. Szewczyk, R. E. Reddy, F. A. Davis, M. M. JoulliE, Tetrahedron Lett. 1999, 40, 455-458.

83 L. Ettouati, A. Ahond, O. Convert, C. Poupat, P. Potier, Pierre, Bull. Soc. Chim. Fr. 1989, 687-694.

84 (R)-N,N-dimethyl-jS-phenylalanine: (a)

E. Winterstein, A. Latrides, Hoppe-Seyler's Z. Physiol. Chem. 1921, 117, 240-283; (b) S. G. Davies, J. Dupont, R. J. E. Easton, Tetrahedron Asymmetry 1990, 1, 279-280.

85 G. Appendino, S. Tagliapietra, H. C. Ozen, P. Gariboldi, B. Gabetta,

86 (a) G. M. Cragg, Med. Chem. Rev. 1998, 18, 315-331; (b) K. C. Nico-laou, W. M. Dai, R. K. Guy, Angew. Chem. Int. Ed. 1994, 33, 15-44.

87 E. Graf, A. Kirfel, G.-J. Wolff, E. Breitmaier, Liebigs Ann. Chem. 1982, 376-381.

88 Free jS-Phe has only been detected in cell-free extracts of T. brevifolia (Floss et al.).

89 Structure: (a) T. P. Hettinger, L. C. Craig, J. Am. Chem. Soc. 1968, 7, 4147-4153; (b) T. P. Hettinger,

Z. Kurylo-Borowska, L. C. Craig, ibid. 1968, 7, 4153-4160. Biosynthesis: (c) Z. Kurylo-Borowska, T. Abramsky, Biochim. Biophys. Acta 1972, 264, 1-10. Edeine D, F: (d) H. Wojciechowska, W. Zgoda, E. Borowski, K. Dziegielewski, S. Ulikowski, J. Antibiot. 1983, 36, 793798.

90 The absolute and relative stereochemistry of the a-methoxy-jS-Tyr moiety was not described: R. Jansen, B. Kunze, H. Reichenbach, G. Hofle, Liebigs Ann. 1996, 285-290.

F. N. M. KUhnle, B. Martinoni, L. Oberer, U. Hommel, H. Widmer, Helv. Chim. Acta 1996, 79, 913-941; (b) D. Seebach, S. Abele, K.

Gademann, B. Jaun, Angew. Chem. Int. Ed. 1999, 111, 1595-1597; (c) T. Hinteemann, D. Seebach, Synlett, 1997, 437-438.

92 M. J. Eggen, G. I. Geüeg, Med. Res. Rev. 2002, 22, 85-101.

93 T. Li, C. Shih, Front. Biotechnol. Pharm. 2002, 3, 172-192.

94 T. C. Stadtman, Adv. Enzymol. Relat. Areas Mol. Biol. 1970, 38, 413-448.

95 Isolation: (a) E. B. Heee, Antimicrob. Agents Chemother. 1962, 201-212. Structure elucidation: (b) S. Nomoto, T. Teshima, T. Wakamiya, T. Shiba, J. Antibiot. 1977, 30, 955-959. Synthetic analogues: (c) R. G. Linde

11, N. C. Biesnee, R. Y. Chandease-kaean, J. Ciancy, R. J. Howe, J. P. Lyssikatos, C. P. MacLeiiand,

T. V. Magee, J. W. Peptitpas, J. P. Rainviiie, W. G. Su, C. B. Vu, D. A. Whippie, Bioorg. Med. Chem. Lett. 1997, 7, 1149-1152 and literature cited therein.

96 E. GEAF, A. KIEFEI, G.-J. WOIFF, E. Beeitmaiee, Liebigs Ann. Chem. 1982, 376-381.

97 (a) I. Ojima, R. Geney, I. M. Ungueeanu, D. Li, IUBMB Life 2002, 53, 269-274; (b) H. M. Deutsch, J. A. Giinski, M. Heenandez, R. D. Haugwitz, V. L. Naeayanan, M. Suffness, L. H. Zaikow, J. Med. Chem. 1989, 32, 788-792; (c) I. Ojima, X. Geng, S. Lin, P. Peea, R. J. Beenacki, Bioorg. Chem. Lett. 2002,

98 G. Taeaboietti, G. Micheietti, M. Rieppi, M. Poii, M. Tueatto, C. Rossi, P. Boesotti, P. Roccabianca, E. Scanziani, M. I. Nicoietti, E. Bombaedeiii, P. Moeazzoni, A. Riva, R. Giavazzi, Clin. Cancer Res. 2002, 8, 1182-1188.

99 M. A. Joedan, I. Ojima, F. Rosas, M. Distefano, L.Wiison, G. Scambia, C. Feeiini, Chem. Biol. 2002, 9, 93-101.

100 Structure: (a) R. Hocquemiiiee, A. CavE, H.-P. Husson, Tetrahedron, 1977, 33, 645-651. Synthesis: (b) R. Hocquemiiiee, A. CavE, H.-P. Husson, Tetrahedron, 1977, 33, 653656.

Helv. Chim. Acta 1982, 65, 2540-2547;

(b) H. H. Wasseeman, H. Matsu-yama, R. P. Robinson, Tetrahedron 2002, 58, 7177-7190. Synthesis or (+)-verbascenine: (c) H. H. Wasseeman, R. P. Robinson, Tetrahedron Lett. 1983, 24, 3669-3672.

102 (17R,18R)-aphelandrine i orantine; (a) A. Guggisbeeg, R. Peewo, M. Hesse, Helv. Chim. Acta 1986, 69, 1012-1016; (b) L. NezbodavA, M. Hesse, K. Deandaeov, C. Weenee, Tetrahedron Lett. 2001, 42, 4139-4141. Isolation: (c) P. DAtwyiee, H. Bossaedt, S. Johne, M. Hesse, Helv. Chim. Acta 1979, 62, 2712-2723.

103 (a) H. O. Beenhaed, I. Kompis, S. Johne, D. Geogee, M. Hesse, H. Schmid, Helv. Chim. Acta 1973, 56, 1266-1303; (b) H. H. Wasseeman, R. P. Robinson, C. G. Caetee, J. Am. Chem. Soc. 1983, 105, 1697-1698.

104 Isolation from Chaenorhinum minus: J.-p. Zhu, A. Guggisbeeg, M. Hesse, Helv. Chim. Acta, 1988, 71, 218-223.

105 (a) K. Deandaeov, A. Guggisbeeg, M. Hesse, Helv. Chim. Acta 2002, 85, 979-989; (b) V. Dimiteov, H. Geneste, A. Guggisbeeg, M. Hesse, Helv. Chim. Acta 2001, 84, 2108-2118;

(c) A. Guggisbeeg, K. Deandaeov, M. Hesse, Helv. Chim. Acta 2000, 83, 3035-3042; (d) L. NezbedovA, K. Deandaeov, C. Weenee, M. Hesse, Helv. Chim. Acta 2000, 83, 2953-2960.

106 (a) T. M. Zabeiskie, J. A. Kiocke, C. M. Ieeiand, A. H. Maecus, T. F. Moiinski, D. J. Fauiknee, C. Xu, J. C. Ciaedy, J. Am. Chem. Soc. 1986, 108, 3123-3124; (b) P. Ceews, L. V. Manes, M. Boehiee, Tetrahedron Lett. 1986, 27, 2797-2800; (c) J. P. Konopeiski, Asymmetric Synthesis of ß-Aryl- and ß-Alkyl-ß-Amino Acids via Enantiomerically Pure Dihydropyrimidi-nones, Enantioselektive Synthesis ofß-Amino Acids, E. Juaeisti, ed., Wiley-VCH, New York, 1997, pp. 249-259;

(d) A. Zampeiia, C. Giannini, C. Debitus, C. Roussakis, M. V. D'Aueia, J. Nat. Prod. 1999, 62, 332-334.

107 (a) J. E. Coieman, R. Van Soest, R. J. Andeesen, R. G. Keisey, J. Nat. Prod. 1999, 62, 1137-1141; (b) W. F. Tinto,

A. J. Lough, S. McLean, W. F. Reynolds, M. Yu, W. R. Chan, Tetrahedron 1998, 54, 4451-4458.

108 (a) Y.-s. Zhen, S.-y. Ming, Y. Bin, T. Otani, H. Saito, Y. Yamada, J. Antibiot. 1989, 42, 1294; (b) K.-i. Yoshida, Y. Minami, T. Otani, Tetrahedron Lett. 1994, 35, 5253-5256; (c) L. Yu, S. Mah, T. Otani, P. Dedon, J. Am. Chem. Soc. 1995, 117, 8877-8878; (d) T. Sasaki, M. Inoue, M. Hirata, Tetrahedron Lett. 2001, 42, 5299-5303.

109 The real reactive, DNA-cleaving, toxophore is a phenylene-1,4-diyl radical that is formed via a Bergman cyclization.

110 Biosynthesis: (a) W. Liu, S. D. Christenson, S. Standage, B. Shen, Science, 2002, 297, 1170-1173; (b) J. S. Thorson, B. Shen, R. E. Whitwam, W. Liu, Y. Li, J. Ahlert, Bioorg. Chem. 1999, 27, 172-188.

111 F. von Nussbaum, P. Spiteller, M. Rüth, W. Steglich, G. Wanner, B. Gamblin, L. Stievano, F. E. Wagner, Angew. Chem. Int. Ed. 1998, 37, 32923295.

112 For a review on Dap (1 Dpr) see: R. Andruszkiewicz, Pol. J. Chem. 1995, 69, 1615-1629.

113 C. J. Schofield, M. W. Walter, ß-Lactam Chemistry, in Amino Acids, Peptides, and Proteins 1999, 30, 335397.

114 (a) K. L. Rinehart, K. Harada, M. Namikoshi, C. Chen, C. A. Harvis, M. H. G. MUNRO, J. W. BLUNT, P. E. Mulligan, V. R. Beasley, A. M. Dahlem, W. W. Carmichael, J. Am. Chem. Soc. 1988, 110, 8557-8558. Synthesis of Adda: (b) C. Pearson, K. L. Rinehart, M. Sugano, J. R. Costerison, Org. Lett. 2000, 2, 29012903; (c) J. S. Panek, T. Hu, J. Org. Chem. 1997, 62, 4914-4915.

115 (a) W. H. Gerwick, L. Tong Tan, N. Sitachitta, The Alkaloids, 2001, 57, 75-184; (b) A. M. Burja, B. Banaigs, E. Abou-Mansour, J. G. Burgess, P. C. Wright, Tetrahedron 2001, 57, 9347-9377.

116 D. J. Faulkner, Nat. Prod. Rep. 2002, 19, 1-48.

Unson, C. A. Bewley, M. J. Garson, Gazz. Chim. Ital. 1993, 123, 301307.

118 H. Sone, T. Nemoto, H. Ishiwata, M. Ojika, K. Yamada, Tetrahedron Lett. 1993, 34, 8449-8452.

119 D. C. Carter, R. E. Moore, J. S. Mynderse, W. P. Niemczura, J. S. Todd, J. Org. Chem. 1984, 49, 236241.

120 R. B. Bates, K. G. Brusoe, J. Burns, S. Caldera, W. Cui, S. Gangwar, M. R. Gramme, K. J. McClure, G. P. Rouen, H. Schadow, C. C. Stessman, S. R. Taylor, V. H. Vu, G. V. Yarick, J. Zhang, G. R. Pettit, R. Bontems, J. Am. Chem. Soc. 1997, 119, 21112113.

121 F. D. Horgen, W. Y. Yoshida, P. J. Scheuer, J. Nat. Prod. 2000, 63, 461467.

122 H. Luesch, P. G. Williams, W. Y. Yoshida, R. E. Moore, V. J. Paul, J. Nat. Prod. 2002, 65, 996-1000.

123 Though kulokekahilide-1 has been isolated from the marine mollusk Philinopsis speciosa, this cytotoxic depsipeptide might originate from dietary cyanobacteria. J. Kimura, Y. Takada, T. Inayoshi, Y. Nakao, G. Goetz, W. Y. Yoshida, P. J. Scheuer, J. Org. Chem. 2002, 67, 1760-1767.

124 L. M. Nogle, W. H. Gerwick, J. Nat. Prod. 2002, 65, 21-24.

125 G. R. Pettit, J. Xu, F. Hogan, M. D. Williams, D. L. Doubek, J. M. Schmidt, R. L. Cerney, M. R. Boyd, J. Nat. Prod. 1997, 60, 752-754.

126 P. G. Williams, W. Y. Yoshida, R. E. Moore, V. J. Paul, J. Nat. Prod. 2002, 65, 29-31.

127 G. R. PETTIT, J.-P. XU, F. HOGAN, R. L. Cerny, Heterocycles 1998, 47, 491-496.

128 J. Rodriguez, R. Fernandez, E. QuiNoa, R. Riguera, C. Debitus, P. Bouchet, Tetrahedron Lett. 1994, 35, 9239-9242.

129 (a) K. Sivonen, W. W. Carmichael, M. Namikoshi, K. L. Rinehart, A. M. Dahlem, S. I. Niemeia, Appl. Envrion. Microbiol. 1990, 56, 2650-2657;

(b) D. P. Botes, A. A. Tuinman, P. L. Wessels, C. C. Viljoen, H. Kruger,

D. H. Williams, S. Santikarn, R. J. Smith, S. J. Hammond, J. Chem. Soc., Perkin Trans. 1 1984, 2311-2318; (c)

G.-B. Trogen, A. Annila, J. Eriksson, M. Kontteli, J. Meriluoto, I. Sethson, J. Zudnek, U. Edlund, Biochemistry 1996, 35, 3197-3205; (d) J. M. Humphrey, J. B. Aggen, A. R. Chamberlin, J. Am. Chem. Soc. 1996, 118, 11759-11770.

130 M. Saito, A. Konno, H. Ishii, H. Saito, F. Nishida, T. Abe, C. Chen, J. Nat. Prod. 2001, 64, 139-141.

131 Isolation: (a) E. Dilip de Silva, D. E. Williams, R. J. Andersen, H. Klix, C. F. B. Holmes, T. M. Allen, Tetrahedron Lett. 1992, 33, 1561-1564. For a recent synthesis see: (b) T. Hu, J. S. Panek, J. Am. Chem. Soc. 2002, 124, 11368-11378; (c) S. M. Bauer, R. W. Armstrong, J. Am. Chem. Soc. 1999, 121, 6355-6366; (d) R. Samy,

H. Y. Kim, M. Brady, P. L. Toogood, J. Org. Chem. 1999, 64, 2711-2728. First Synthesis: (e) R. L. Valenteko-vich, S. L. Schreiber, J. Am. Chem. Soc. 1995, 117, 9069-9070.

132 G. L. HELMS, R. E. MOORE, W. P. Niemczura, G. M. L. Patterson, K. B. Tomer, M. L. Gross, J. Org. Chem. 1988, 53, 1298-1307.

133 H. Luesch, G. G. Harrigan, G. Goetz, F. D. Horgen, Curr. Med. Chem. 2002, 9, 1791-1806.

E. Moore, D. G. Nagle, P. U. Park, J. Biggs, V. J. Paul, S. L. Mooberry,

T. H. Corbett, F. A. Valeriote, J. Nat. Prod. 1998, 61, 1221-1225.

135 Y. Unedo, S. Nagata, T. Tsutsumi, A. Hasegawa, M. F. Watanabe, H.-D. Park, G.-C. Chen, G. Chen, S.-Z. Yu, Carcinogenesis 1996, 17, 1317-1321.

136 C. A. Bewley, D. J. Faulkner, Angew. Chem. Int. Ed. 1998, 37, 2162-2178.

137 (a) M. Konishi, M. Nishino, K. Saitoh, T. Miyaki, T. Oki, K. Kawaguchi, J. Antibiot. 1989, 42, 1749-1755; (b) D. Jethwaney, M. Hofer, R. K. Khaware, R. Prasad, Microbiology 1997, 143, 397-404; (c) J. Capobianco, D. Z. Zakula, M. L. Coen, R. C. Goldman, Biochem. Biophys. Res. Commun. 1993, 190, 1037-1044.

138 (a) D. Jethwaney, M. Hofer, R. K. Khaware, R. Prasad, Microbiology 1997, 143, 397-404; (b) J. Capobianco, D. Z. Zakula, M. L. Coen, R. C. Goldman, Biochem. Biophys. Res. Commun. 1993, 190, 1037-1044.

139 In these cases the "formal" j-amino acid relationship often is a result of late stage condensation or cyclization reactions (e.g. Mannich-type, Pictet-Spengler) within the biosynthesis: Typical examples are cocaine and correlated tropane alkaloids, Catharanthus alkaloids or Iboga alkaloids like heyneanine.

140 T. Henkel, R. M. Brunne, H. MUller, F. Reichel, Angew. Chem. Int. Ed. 1999, 38, 643-647.

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