Ansamitocin Libraries by Combining Mutasynthesis with Chemical Synthesis; A New Version of Total Synthesis

Florian Taft; Simone Eichner; Tobias Knobloch; Kirsten Harmrolfs; Jekaterina Hermane; Andreas Kirschning

doi:10.1055/s-0031-1290695

Synlett, Table of Contents

Synlett 2012; 23(10): 1416-1426
DOI: 10.1055/s-0031-1290695

account

Ansamitocin Libraries by Combining Mutasynthesis with Chemical Synthesis; A New Version of Total Synthesis

Florian Taft

Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011 Email: andreas.kirschning@oci.uni-hannover.de

,

Simone Eichner

Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011 Email: andreas.kirschning@oci.uni-hannover.de

,

Tobias Knobloch

Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011 Email: andreas.kirschning@oci.uni-hannover.de

,

Kirsten Harmrolfs

Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011 Email: andreas.kirschning@oci.uni-hannover.de

,

Jekaterina Hermane

Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011 Email: andreas.kirschning@oci.uni-hannover.de

,

Andreas Kirschning*

Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011 Email: andreas.kirschning@oci.uni-hannover.de

› Author Affiliations

Abstract

All articles of this category

Abstract

Blocked mutants of Actinosynnema pretiosum, the producer of the highly cytotoxic antitumor agent ansamitocin, serve as powerful tools that allow synthetic chemists to generate natural product libraries. The power of this approach can be dramatically expanded when mutasynthesis is combined with chemical synthesis. This report provides illustrative examples of the application of this strategy to produce libraries based on the ansamycin antibiotics.

1 Introduction

2 Mutasynthesis — A Powerful Strategy for Accessing New Ansamitocin Derivatives

3 Mutasynthesis Combined with Semisynthesis; Further Generalization of a Diversity Concept

4 Mutasynthesis with Advanced Synthetic Intermediates

5 Blocked Mutants as Tools for Biosynthetic Studies of Ansamitocins

6 Conclusions

Key words

ansamitocins - antitumor agents - biosynthesis - mutasynthesis - semisynthesis

Full Text

References

References
1 Kupchan SM, Komoda Y, Court WA, Thomas GJ, Smith RM, Karim A, Gilmore CJ, Haltiwanger RC, Bryan RF. J. Am. Chem. Soc. 1972; 94: 1354
2 Higashide E, Asai M, Ootsu K, Tanida S, Kozai Y, Hasegawa T, Kishi T, Sugino Y, Yoneda M. Nature 1977; 270: 721

For reviews, see:
3a Floss HG, Yu T.-w, Arakawa K. J. Antibiot. 2011; 64: 35
3b Kirschning A, Harmrolfs K, Knobloch T. C. R. Chim. 2008; 11: 1523
3c Cassady JM, Chan KK, Floss HG, Leistner E. Chem. Pharm. Bull. 2004; 52: 1
3d Komoda Y, Kishi T. Anticancer Agents Based on Natural Product Models . Douros J, Cassady JM. Academic Press; New York: 1980: 353-389

4 Annual Report to the FDA by DCT, NCI, on Maytansine, NSC 153858, IND 11857, February 1984

Disulfide-linked antibody–maytansinoid conjugates were reported by Chari and co-workers, see:
5a Chari RV. J, Martell BA, Gross JL, Cook SB, Shah SA, Blättler WA, McKenzie SJ, Goldmacher VS. Cancer Res. 1992; 52: 127
5b Widdison WC, Wilhelm SD, Cavanagh EE, Whiteman KR, Leece BA, Kovtun Y, Goldmacher VS, Xie H, Steeves RM, Lutz RJ, Zhao R, Wang L, Blättler WA, Chari RV. J. J. Med. Chem. 2006; 49: 4392
5c Erickson HK, Park PU, Widdison WC, Kovtun YV, Garrett LM, Hoffman K, Lutz RJ, Goldmacher VS, Blättler WA. Cancer Res. 2006; 66: 4426
5d Ladino CA, Chari RV. J, Bourret LA, Kedersha NL, Goldmacher VS. Int. J. Cancer 1997; 73: 859

6a Lambert JM. Curr. Opin. Pharmacol. 2005; 5: 543
6b Kratz F, Ajaj KA, Warnecke A. Expert Opin. Invest. Drugs 2007; 16: 1037

7a Wu AM, Senter PD. Nat. Biotechnol. 2005; 23: 1137
7b Chari RV. Acc. Chem. Res. 2008; 41: 98

8 Low PS, Henne WA, Doorneweerd DD. Acc. Chem. Res. 2008; 41: 120

9a Arap W, Pasqualini R, Ruoslahti E. Science 1998; 279: 377
9b Janssen ML, Oyen WJ, Dijkgraaf I, Massuger LF, Frielink C, Edwards DS, Rajopadhye M, Boonstra H, Corstens FH, Boerman OC. Cancer Res. 2002; 62: 6146
9c Haubner R, Wester HJ, Burkhart F, Senekowitsch-Schmidtke R, Weber W, Goodman SL, Kessler H, Schwaiger M. Bioconjugate Chem. 2001; 12: 84

10a Niculescu-Duvaz I. Curr. Opin. Mol. Ther. 2010; 12: 350
10b Junutula JR, Flagella KM, Graham RA, Parsons KL, Ha E, Raab H, Bhakta S, Nguyen T, Dugger DL, Li G, Mai E, Phillips GD, Hiraragi H, Fuji RN, Tibbitts J, Vandlen R, Spencer SD, Scheller RH, Polakis P, Sliwkowski MX. Clin. Cancer Res. 2010; 16: 4769

11 Asai M, Mizuta E, Izawa M, Haibara K, Kishi T. Tetrahedron 1979; 35: 1079
12 Kawai A, Akimoto H, Kozai Y, Ootsu K, Tanida S, Hashimoto N, Nomura H. Chem. Pharm. Bull. 1984; 32: 3441
13 Widdison WC, Chari RV. J. US. Patent 20,070,112,188, 2007
14 Widdison WC, Wilhelm SD, Cavanagh EE, Whiteman KR, Leece BA, Kovtun Y, Goldmacher VS, Xie H, Stevens RM, Lutz RJ, Zhao R, Wang L, Blättler WA, Chari RV. J. J. Med. Chem. 2006; 49: 4392
15 Miyashira O, Akimoto H. US. Patent 4,256,746, 1981
16 Kawai A, Akimoto H, Hashimoto N, Nomura H. Chem. Pharm. Bull. 1984; 32: 2194

17a Nakahama K, Izawa M, Asai M, Kida M, Kishi T. J. Antibiot. 1981; 34: 1581
17b Izawa M, Nakahama K, Kasahara F, Asai M, Kishi T. J. Antibiot. 1981; 34: 1587
17c Izawa M, Wada Y, Kasahara F, Asai M, Kishi T. J. Antibiot. 1981; 34: 1591

18a Tanida S, Izawa M, Hasegawa T. J. Antibiot. 1981; 34: 489
18b Izawa M, Tanida S, Asai M. J. Antibiot. 1981; 34: 496

19 Meyers AI, Reider PJ, Campell AL. J. Am. Chem. Soc. 1980; 102: 6597 ; and references cited therein
20 Corey EJ, Weigel LO, Chamberlin AR, Cho H, Hua DH. J. Am. Chem. Soc. 1980; 102: 6615 ; and references cited therein
21 Isobe M, Kitamura M, Goto T. J. Am. Chem. Soc. 1982; 104: 4997 ; and references cited therein
22 Benechie M, Khuong-Huu F. J. Org. Chem. 1996; 61: 7133 ; and references cited therein

For reviews, see:
23a Weist S, Süssmuth RD. Appl. Microbiol. Biotechnol. 2005; 68: 141
23b Kirschning A, Taft F, Knobloch T. Org. Biomol. Chem. 2007; 3245

24a Rinehart KL. Jr. Pure Appl. Chem. 1977; 49: 1361
24b Rinehart KL. Jr. Jpn. J. Antibiot. 1979; 32: suppl. S32-46

25a Gregory MA, Petkovic H, Lill RE, Moss SJ, Wilkinson B, Gaisser S, Leadlay PL, Sheridan RM. Angew. Chem. Int. Ed. 2005; 44: 4757 ; Angew. Chem. 2005, 117, 4835
25b Ziehl M, He J, Dahse H.-M, Hertweck C. Angew. Chem. Int. Ed. 2005; 44: 1202 ; Angew. Chem. 2005, 117, 1226

26 Spiteller P, Bai L, Shang G, Carroll BJ, Yu T.-W, Floss HG. J. Am. Chem. Soc. 2003; 125: 14236
27 Yu T.-W, Bai L, Clade D, Hoffmann D, Toelzer S, Trinh KQ, Xu J, Moss SJ, Leistner E, Floss HG. Proc. Natl. Acad. Sci. U.S.A. 2002; 99: 7968
28 Taft F, Brünjes M, Floss HG, Czempinski N, Grond S, Sasse F, Kirschning A. ChemBioChem 2008; 9: 1057
29 Meyer A, Brünjes M, Taft F, Frenzel T, Sasse F, Kirschning A. Org. Lett. 2007; 9: 1489
30 Knobloch T, Harmrolfs K, Taft F, Thomaszewski B, Sasse F, Kirschning A. ChemBioChem 2011; 12: 540

N-Glucosylated ansamitocin derivatives have been reported as byproducts during solid agar fermentations before, see:
31a Ma J, Zhao P.-J, Shen Y.-M. Arch. Pharmacal. Res. 2007; 30: 670
31b Lu C, Bai L, Shen Y. J. Antibiot. 2004; 57: 348
31c Snipes CE, Duebelbeis DO, Olson M, Hahn DR, Dent WH. III, Gilbert JR, Werk TL, Davis GE, Lee-Lu R, Graupner PR. J. Nat. Prod. 2007; 70: 1578

32 Taft F., Harmrolfs K., Nickeleit I., Heutling A., Kiene M., Malek N., Sasse F., Kirschning A. Chem. Eur. J. 2012, 18, 860
33 Eichner S., Knobloch T., Floss H. G., Fohrer J., Harmrolfs K., Hermane J., Schulz A., Sasse F., Spiteller P., Taft F., Kirschning A. Angew. Chem. Int. Ed. 2012, 51, 752; Angew. Chem. 2012, 124, 776

34a Kim C.-G, Yu TW, Fryhle CB, Handa S, Floss HG. J. Biol. Chem. 1998; 273: 6030
34b Arakawa K, Müller R, Mahmud T, Yu T.-W, Floss HG. J. Am. Chem. Soc. 2002; 124: 10644

35 Pompeo F, Mushtaq A, Sim E. Protein Expression Purif. 2002; 24: 138

36a August PR, Tang L, Yoon YJ, Ning S, Müller R, Yu TW, Taylor M, Hoffmann D, Kim CG, Zhang X, Hutchinson CR, Floss HG. Chem. Biol. 1998; 5: 69
36b Rascher A, Hu Z, Viswanathan N, Schirmer A, Reid R, Nierman WC, Lewis M, Hutchinson CR. FEMS Microbiol. Lett. 2003; 218: 223

37 Chemically, amide synthases perform analogous transformations to the thioesterases responsible for macrolactonization and macrolactamization of polyketides and nonribosomal peptides (NRP)
38 Harmrolfs K, Brünjes M, Dräger G, Floss HG, Sasse F, Taft F, Kirschning A. ChemBioChem 2010; 11: 2517
39 Fenzel T, Brünjes M, Quitschalle M, Kirschning A. Org. Lett. 2006; 8: 135
40 Kubota T, Brünjes M, Frenzel T, Xu J, Kirschning A, Floss HG. ChemBioChem 2006; 7: 1221
41 Taft F, Brünjes M, Knobloch T, Floss HG, Kirschning A. J. Am. Chem. Soc. 2009; 131: 3812
42 Trost BM, McEachern EJ, Toste FD. J. Am. Chem. Soc. 1998; 120: 12702