RSS-Feed abonnieren
Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.
https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000083.xml
Synlett 2013; 24(9): 1097-1100
DOI: 10.1055/s-0033-1338414
DOI: 10.1055/s-0033-1338414
letter
Asymmetric Synthesis of 1-Aza-4-deoxypicropodophyllotoxin
Weitere Informationen
Publikationsverlauf
Received: 10. Februar 2013
Accepted after revision: 25. März 2013
Publikationsdatum:
12. April 2013 (online)
Abstract
In our search for new easily accessible analogues based on the natural product podophyllotoxin, we synthesized 1-aza-4-deoxypicropodophyllotoxin in good overall yield and excellent enantioselectivity. The synthesis was centered around a direct asymmetric Mannich reaction using d-proline as the key step for introduction of the chiral centres. Our synthesis of 1-aza-4-deoxypodophyllotoxin was hindered through the increased instability towards epimerization of the C2 position. We did, however, synthesized a new scaffold based on the opened lactone analogue.
Key words
Mannich bases - asymmetric catalysis - amino aldehydes - enantioselectivity - total synthesisSupporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
-
References and Notes
- 1 Noguchi T, Kawanami M. Yakugaku Zasshi 1940; 60: 629
- 2 Keller-Juslen C, Kuhn M, Von Wartburg A, Stähelin H. J. Med. Chem. 1971; 14: 936
- 3a Ikeda R, Nagao T, Okabe H, Nakano Y, Matsunaga H, Katano M, Mori M. Chem. Pharm. Bull. 1998; 46: 871
- 3b Subrahmanyam D, Renuka B, Kumar GS, Vandana V, Deevi DS. Bioorg. Med. Chem. Lett. 1999; 9: 2131
- 3c Kim Y, Kim SB, You YJ, Ahn BZ. Planta Med. 2002; 68: 271
- 3d Masuda T, Oyama Y, Yonemori S, Takeda Y, Yamazaki Y, Mizuguchi S, Nakata M, Tanaka T, Chikahisa L, Inabak Y, Okada Y. Phytother. Res. 2002; 16: 353
- 3e Muto N, Tomokuni T, Haramoto M, Tatemoto H, Nakanishi T, Inatomi Y, Murata H, Inada A. Biosci., Biotechnol., Biochem. 2008; 72: 477
- 4a Gupta RS. Cancer Res. 1983; 43: 505
- 4b Loike JD. Cancer Res. 1978; 38: 2688
- 4c Suh SJ, Kim JR, Jin UH, Choi HS, Chang YC, Lee YC, Kim SH, Lee IS, Moon TS, Chang HW, Kim CH. Vasc. Pharmacol. 2009; 51: 13
- 4d Yong YJ, Shin SY, Lee YH, Lim YH. Bioorg. Med. Chem. Lett. 2009; 19: 4367
- 4e Shin SY, Yong Y, Kim CG, Lee YH, Lim Y. Cancer Lett. 2010; 287: 231
- 5a Sudo K, Konno K, Shigeta S, Yokota T. Antiviral Chem. Chemother. 1998; 9: 263
- 5b Ikeda R, Nagao T, Okabe H, Nakano Y, Matsunaga H, Katano M, Mori M. Chem. Pharm. Bull. 1998; 46: 871
- 5c Chen JJ, Chang YL, Teng CM, Chen IS. Planta Med. 2000; 66: 251
- 5d Lin CX, Lee E, Jin MH, Yook J, Quan Z, Ha K, Moon TC, Kim MJ, Kim KJ, Lee SH, Chang HW. Planta. Med. 2006; 72: 786
- 5e Lee SH, Son MJ, Ju HK, Lin CX, Moon TC, Choi HG, Son JK, Chang HW. Biol. Pharm. Bull. 2004; 27: 786
- 5f Lin CX, Son MJ, Ju HK, Moon TC, Lee E, Kim SH, Kim MJ, Son JK, Lee SH, Chang HW. Planta. Med. 2004; 70: 474
- 5g Inamori Y, Kato Y, Kubo M, Baba K, Ishida T, Nomoto K, Kozawa M. Chem. Pharm. Bull. 1985; 33: 704
- 6 Axelson M, Larsson O. WO 2009/157858 A1, 2009
- 7 Kumar A, Kumar V, Alegria AE, Malhotra SV. Curr. Med. Chem. 2011; 18: 3853
- 8a Hitotsuyanagi Y, Kobayashi M, Fukuyo M, Takeya K, Itokawa H. Tetrahedron Lett. 1997; 39: 8295
- 8b Hitotsuyanagi Y, Fukuyo M, Tsuda K, Kobayashi M, Ozeki A, Itokawa H, Takeya K. Bioorg. Med. Chem. Lett. 2000; 10: 315
- 9 Tratat C, Giorgi-Renault S, Husson HP. Org. Lett. 2002; 4: 3187
- 10a Notz W, Tanaka F, Watanabe SI. Chowdari N. S, Turner JM, Thayumanavan R, Barbas CF. III. J. Org. Chem. 2003; 68: 9624
-
10b Uchida T, Rodriquez M, Schreiber SL. Org. Lett. 2009; 11: 1559
- 10c Zhao G.-L, Córdova A. Tetrahedron Lett. 2006; 42: 7417
- 10d Watanabe S.-I, Córdova A, Tanaka F, Barbas CF. III. Org. Lett. 2002; 4: 4519
- 10e Martin-Rapún R, Fan X, Sayalero S, Bahramnejad M, Cuevas F, Pericàs MA. Chem. Eur. J. 2011; 17: 8780
- 10f Chowdari NS, Suri JT, Barbas CF. III. Org. Lett. 2004; 6: 2507
- 11 Ferreira WS, Freire-de-Lima L, Saraiva VB, Alisson-Silva F, Mendonca-Previato L, Previato JO, Echevarria A, Freire de Lima ME. Bioorg. Med. Chem. 2008; 16: 2984
- 12 Omura K, Swern D. Tetrahedron 1978; 34: 1651
- 13 Borrione E, Prato M, Scorrano G, Stivanello M, Lucchini V. J. Heterocycl. Chem. 1988; 25: 1831
- 14 Lower catalyst loading led to a lower enantioselectivity, 10% catalyst loading gave 72% ee, 20% catalyst loading gave 88% ee.
- 15 This lower temperature is necessary to avoid epimerization of the α-carbon next to the aldehyde during the reduction.
- 16 List B, Pojarliev P, Biller WT, Martin HJ. J. Am. Chem. Soc. 2002; 124: 827
- 17 Yields obtained for other ligands; Xphos: 39%, Ruphos: 42%, Brettphos: 21%, t-BuXphos: 14%.
- 18 Yields for copper reactions using CuI with ligand: TMEDA: 9%, 4-hydroxyproline: 12%.
- 19 Gensler WJ, Gatsonis CD. J. Org. Chem. 1966; 31: 4004
- 20 Triphenylmethylsodium is an unstable reagent and is therefore not commercially available. We were unable to prepare the reagent due to safety regulations of our department concerning the use of mercury. For the synthesis of triphenylmethylsodium, see: Renfrow WB. Jr, Hauser CR. Org. Synth. 1943; 2: 607
- 21 Kende AS, King ML, Curran DP. J. Org. Chem. 1981; 46: 2826
- 22 Zeynizadeh B, Faraji F. Bull. Korean Chem. Soc. 2008; 29: 76
- 23 DiLauro M, Seo W, Phillips ST. J. Org. Chem. 2011; 76: 7352
- 24 Bush EJ, Jones DW. J. Chem. Soc., Chem. Commun. 1993; 1200
- 25 Subrahmanyam D, Renuka B, Rao CV. L, Sagar PS, Deevi DS, Babu JM, Vyas K. Bioorg. Med. Chem. Lett. 1998; 8: 1391
For more recent examples concerning this reaction, see: