4,5-Disubstituted 1-Methylimidazoles via Cyclization of Defined α-Aminoketones: Synthesis of Fungerin and Analogues I

Daniel Przybyla; Udo Nubbemeyer

doi:10.1055/s-0036-1588324

Synthesis, Table of Contents

Synthesis 2017; 49(04): 770-774
DOI: 10.1055/s-0036-1588324

paper

4,5-Disubstituted 1-Methylimidazoles via Cyclization of Defined α-Aminoketones: Synthesis of Fungerin and Analogues I

Daniel Przybyla

Institut für Organische Chemie/Johannes Gutenberg-Universität Mainz, Duesbergweg 10–14, 55128 Mainz, Germany Email: nubbemey@uni-mainz.de

,

Udo Nubbemeyer*

Institut für Organische Chemie/Johannes Gutenberg-Universität Mainz, Duesbergweg 10–14, 55128 Mainz, Germany Email: nubbemey@uni-mainz.de

› Author Affiliations

Abstract

All articles of this category

Abstract

A protocol for the chemoselective synthesis of the fungal metabolite fungerin has been developed. First the required N-methyl α-aminoketone was generated starting from sarcosine, propiolic acid, and prenyl bromide. Marckwald thioimidazole cyclization and subsequent sulfur removal delivered the target fungerin as well as an analogue, respectively, displaying defined substitution patterns.

Key words

imidazole - α-aminoketone - Marckwald synthesis - regioselective synthesis - natural product

Full Text

References

References

For selected examples, see:

1a Shangguan N, Joullié MM. Tetrahedron Lett. 2009; 50: 6755
1b Cho H.-W, Oh C.-H, Lee J.-S, Choi J.-Hu, Choi J.-Hy. Arch. Pharm. (Weinheim) 2003; 336: 495
1c Simpson MG, Pittelkow M, Watson SP, Sanders JK. M. Org. Biomol. Chem. 2010; 8: 1181
1d Sonegawa M, Yokota M, Tomiyama H, Tomiyama T. Chem. Pharm. Bull. 2006; 54: 706
1e Bridson PK, Huang H, Lin X. J. Chem. Soc., Perkin Trans 1 1996; 2257
1f Kanoh K, Kohno S, Katada J, Takahashi J, Uno I, Hayashi Y. Bioorg. Med. Chem. 1999; 7: 1451

For selected examples, see:

2a Subrayan RP, Thurber EL, Rasmussen PG. Tetrahedron 1994; 50: 2641
2b Smalley TL. Jr, Boggs S, Caravella JA, Chen L, Creech KL, Deaton DN, Kaldor I, Parks DJ. Bioorg. Med. Chem. Lett. 2015; 25: 280
2c Yasuda N, Nakamura A, Tsuboi M. J. Heterocycl. Chem. 1987; 24: 303
2d Lam BL, Wellman GR, Labaw CS. J. Org. Chem. 1982; 47: 144

3a Bredereck H, Theilig G. Chem. Ber. 1953; 86: 88
3b Kimura T, Watanabe N, Matsui M, Hayashi K, Tanaka H, Ohtsuka I, Saeki T, Kogushi M, Kabayashi H, Akasaka K, Yamagishi Y, Saitou I, Yamatsu I. J. Med. Chem. 1993; 36: 1641
3c Review: Bredereck H, Gompper R, Schuh G, Theilig G. Angew. Chem. 1959; 71: 753

4a Su Z, Peng L, Melander C. Tetrahedron Lett. 2012; 53: 1204
4b Aberle NS, Lessene G, Watson KG. Org. Lett. 2006; 8: 419
4c Itoh T, Matsuya Y, Nagata K, Ohsawa A. Chem. Pharm. Bull. 1997; 45: 1547
4d Boehm JC, Gleason JG, Pendrak I, Sarau HM, Schmidt DB, Foley JJ, Kingsbury WD. J. Med. Chem. 1993; 36: 3333

5a Marckwald W. Ber. Dtsch. Chem. Ges. 1892; 25: 2354
5b Gompper R. Chem. Ber. 1956; 89: 1762
5c Xi N, Xu S, Cheng Y, Tasker AS, Hungate RW, Reider PJ. Tetrahedron Lett. 2005; 46: 7315
5d Laufer SA, Hauser DR. J, Liedke AJ. Synthesis 2008; 253
5e Dhawas AK, Thakare T. Indian J. Heterocycl. Chem. 2012; 21: 217

6a Visconti A, Solfrizzo M. J. Agric. Food Chem. 1994; 42: 195
6b Solfrizzo M, Visconti A. Toxicol. in Vitro 1994; 8: 461
6c Visconti A. Solfrizzo, M. Food Addit. Contam. Part A 1995; 12: 515

7a Kato Y, Koshino H, Uzawa J, Anzai K. Biosci. Biotech. Biochem. 1996; 60: 2081
7b Höller U, Wright AD, Matthee GF, Konig GM, Dreager S, Aust H.-J, Schulz B. Mycol. Res. 2000; 104: 1354
7c Uchida R, Imasato R, Yamaguchi Y, Masuma R, Shiomi K, Tomoda H, Omura S. J. Antibiot. 2005; 58: 804
7d Putri SP, Ishido K, Kinoshita H, Kitani S, Ihara F, Sakihama Y, Igarashi Y, Nihira T. J. Biosci. Bioeng. 2014; 117: 557

8 Rieder JM, Lepschy J. Tetrahedron Lett. 2002; 43: 2375
9 Hydroxyfungerin B displays the original visoltricin backbone. However, until now, visoltricin had not been isolated from natural sources.
10 Koizumi Y, Arai M, Tomoda H, Omura S. J. Antibiot. 2004; 57: 415
11 Benhida R, Lezama R, Fourrey J.-L. Tetrahedron Lett. 1998; 39: 5963
12 Suh Y.-G, Seo S.-Y, Jung J.-K, Parka O.-H, Jeon R.-O. Tetrahedron Lett. 2001; 42: 1691

Sarcosine methyl ester hydrochloride:

13a O’Connell JF, Parquette J, Yelle WE, Wang W, Rapoport H. Synthesis 1988; 767
13b Otto N, Opatz T. Beilstein J. Org. Chem. 2012; 8: 1105
13c Croft AK, Foley MK. Org. Biomol. Chem. 2008; 6: 1594

N-Boc sarcosine methyl ester:

14a Maeda T, Makino K, Iwasaki M, Hamada Y. Chem. Eur. J. 2010; 16: 11954
14b Reichard GA, Alaimo CA, Shih N.-J, Ting PC, Carruthers NI, Lavey BJ. Patent EP 1032561, 2000

For glycine ester enolate alkylations, see:

15a Dellaria JF. Jr, Santarsiero BD. J. Org. Chem. 1989; 54: 3916
15b Dellaria JF. Jr, Santarsiero BD. Tetrahedron Lett. 1988; 29: 6079

16a Synthesis of N-Boc C-prenyl sarcosine methyl ester: Court JJ, Desai RC, Hlasta DJ. US Patent 5494925, 1996
16b Data of N-Boc N-methylphenylalanine methyl ester: Dinh TQ, Du X, Armstrong RW. J. Org. Chem. 1996; 61: 6606

Synthesis of N-Boc N-methylphenylalanine Weinreb amide:

17a Tae HS, Hines J, Schneekloth AR, Crews CM. Bioorg. Med. Chem. 2011; 19: 1708
17b Williams JM, Jobson RB, Yasuda N, Marchesini G, Dolling U.-H, Grabowski EJ. Tetrahedron Lett. 1995; 36: 5461

3-Iodoacrylic acid:

18a Abarbri M, Parrain JL, Cintrat J.-C, Duchêne A. Synthesis 1996; 82

For ester and ortho ester, see:

18b Suh Y.-G, Jung J.-K, Seo S.-Y, Min K.-H, Shin D.-Y, Lee Y.-S, Kim SH, Park H.-J. J. Org. Chem. 2002; 67: 4127
18c Zhdanko AG, Nenajdenko VG. J. Org. Chem. 2009; 74: 884

19 In analogy to ref. 12, maintenance of the orthoester moiety was achieved applying aqueous workup under basic (buffered) conditions (pH >7).
20 Nudelman A, Bechorl Y, Falb E, Fischerl B, Wexler BA, Nudelman A. Synth. Commun. 1998; 28: 471
21 Norris TO, McKee RL. J. Am. Chem. Soc. 1955; 77: 1056

22a Spero GP, McIntosh AV. Jr, Levin RH. J. Am. Chem. Soc. 1948; 70: 1907
22b Fraser MM, Raphael RA. J. Chem. Soc. 1952; 226

23a Grivas S, Ronne E. Acta Chem. Scand. 1995; 49: 225
23b Schantl JG, Lagoja IM. Heterocycles 1998; 48: 929

Supplementary Material

Supporting Information