Synthesis of Azido Analogues of Medermycin

Margaret A. Brimble; Roger M. Davey; Malcolm D. McLeod

doi:10.1055/s-2002-32955

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Synlett 2002(8): 1318-1322
DOI: 10.1055/s-2002-32955

LETTER

Synthesis of Azido Analogues of Medermycin

Margaret A. Brimble*^a, Roger M. Davey^b, Malcolm D. McLeod^b
^a Department of Chemistry, University of Auckland, 23 Symonds St., Auckland, New Zealand
Fax: +64(9)3737422; e-Mail: m.brimble@auckland.ac.nz;
^b School of Chemistry, F11, Science Rd., Camperdown, NSW 2006, Australia

Further Information

Publication History

Received 5 June 2002
Publication Date:
25 July 2002 (online)

Abstract
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Abstract

The synthesis of azido analogues 2a,2b of the pyranonaphthoquinone antibiotic medermycin 1 has been achieved in eight steps from naphthol 8 and azido glycosyl sugar 7 in 9.3% overall yield. Key steps include the direct BF₃·Et₂O promoted C-glycosylation of naphthol 8, introduction of an acetyl group onto a bromonaphthoquinone via Stille coupling with (α-ethoxy-vinyl)tributyltin, furofuran annulation of a naphthoquinone to a furonaphthofuran using 2-trimethylsilyloxyfuran 5 and oxidative rearrangement of a furonaphthofuran to a furonaphthopyran.

Key words

pyranonaphthoquinone antibiotics - C-glycoside - amino sugar - Stille coupling - naphthoquinone

References

1 Takano S. Hasuda K. Ito A. Koide Y. Ishii F. Haneda I. Chihara S. Koyami T. J. Antibiot. 1976, 28: 765

Google Scholar
2a Okabe T. Namoto K. Funabashi H. Okuda S. Suzuki H. Tanaka N. J. Antibiot. 1985, 38: 1333

Google Scholar
2b Tanaka N. Okabe T. Isono F. Kashiwagi M. Namoto K. Takahashi M. Shimazu A. Nishimura T. J. Antibiot. 1985, 38: 1327

Google Scholar
3 Tanaka N. inventors; Jpn. Kokai Tokkyo Koho JP 62010086. ; Chem. Abstr. 1987, 106, 212564u
4 Nakagawa A. Fukamachi N. Yamaki K. Hayashi M. Ohishi S. Kobayashi B. Omura S. J. Antibiot. 1987, 40: 1075

Crossref PubMed Google Scholar
5a Nomoto K. Okabe T. Suzuki H. Tanaka N. J. Antibiot. 1988, 41: 1124 ; Chem. Abstr. 1988, 109, 142155x

Google Scholar
5b Medentsev AG. Akimenko VK. Biokhimiya 1988, 53: 289 ; Chem. Abstr. 1988, 108, 201575p

Google Scholar
5c Medentsev AG. Maslov AN. Akimenko VK. Biokhimiya 1990, 55: 1766 ; Chem. Abstr. 1990, 114, 37482g

Google Scholar
6 Brimble MA. Duncalf LJ. Nairn MR. Nat. Prod. Rev. 1999, 16: 267

Google Scholar
7 Tatsuta K. Ozeki H. Yamaguchi M. Tanaka M. Okui T. Tetrahedron Lett. 1990, 31: 5495

Crossref Google Scholar
8 Moore HW. Czerniak R. Med. Res. Rev. 1981, 1: 249

Crossref PubMed Google Scholar
9 Brimble MA. Pure Appl. Chem. 2000, 72: 1635

Google Scholar
10 Brimble MA. Stuart SJ. J. Chem. Soc., Perkin Trans. 1 1990, 881

Crossref Google Scholar
11 Brimble MA. Lynds SM. J. Chem. Soc., Perkin Trans. 1 1994, 493

Crossref Google Scholar
For recent reviews on C-glycosylation see:
12a Postema MHD. Tetrahedron 1992, 40: 8545

Crossref Google Scholar
12b Jaramillo C. Knapp S. Synthesis 1994, 1

Crossref Google Scholar
12c Levy DE. Tang C. The Chemistry of C-Glycosides Pergamon Press; Oxford: 1995.

Crossref Google Scholar
12d Du Y. Lindhardt RJ. Tetrahedron 1998, 54: 9913

Crossref Google Scholar
13 Brimble MA. Brenstrum TJ. J. Chem. Soc., Perkin Trans. 1 2001, 1624

Crossref Google Scholar
14 Florent J.-C. Monneret C. J. Chem. Soc., Chem. Commun. 1987, 1171

Crossref Google Scholar
15 Abbaci B. Florent J.-C. Monneret C. Bull. Soc. Chim. Fr. 1989, 5

Google Scholar
16 Fraser-Reid B. Kelly DR. Tulshian DB. Ravi PS. J. Carbohydr. Chem. 1983, 2: 105

Crossref Google Scholar
18 Kosugi M. Sumiya T. Obara Y. Suzuki M. Sano H. Migita T. Bull. Chem. Soc. Jpn. 1987, 60: 767

Crossref Google Scholar
19 Staudinger H. Meyer J. Helv. Chim. Acta 1919, 2: 635

Crossref Google Scholar

17

Unambiguous confirmation of the regiochemical assignment for this bromination step was achieved by preparing 3-bromonaphthalene 14 independently via ortho-bromination of naphthol 17 (Figure).

20

3a,3b: yellow oil; [found (EI): M⁺, 511.1590. C₂₅H₂₅N₃O₉ requires M⁺, 511.1591]; IR(film) cm^-1 3502 (OH), 2936, 2100 (N₃), 1775 (γ-lactone C=O), 1743 (ester C=O); δ_H (400 MHz, CDCl₃): 7.80 (d, 1 H, J _2,1 = 8.6 Hz, H-2), 7.79 (d, 1 H, J _2,1 = 8.6 Hz, H-2*), 7.75 (d, 1 H, J _1,2 = 8.6 Hz, H-1*), 7.73 (d, 1 H, J _1,2 = 8.6 Hz , H-1), 6.46 (d, 1 H, J _6b,9a = 6.3 Hz, H-6b*), 6.45 (d, 1 H, J _6b,9a = 6.3 Hz, H-6b), 5.53-5.50 (m, 1 H, H-9a/H-9a*), 5.04 (dd, 1 H, J ₁ _′ _,2 _′ _ax = 12.3 Hz and J ₁ _′ _,2 _′ _eq = 2.0 Hz, H-1′*), 5.01 (dd, 1 H, J ₁ _′ _,2 _′ _ax = 11.4 Hz and J ₁ _′ _,2 _′ _eq = 1.9 Hz, H-1′), 4.79 (dd, 1 H, J ₄ _′ _,3 _′ = J ₄ _′ _,5 _′ = 9.6 Hz, H-4′*), 4.76 (dd, 1 H, J ₄ _′ _,3’ = J _4’,5’ = 9.6 Hz, H-4′), 3.93 (s, 3 H, OMe), 3.92 (s, 3 H, OMe), 3.81-3.64 (m, 2 H, H-3′/H-3′* and H-5′/H-5′*), 3.15-3.12 (m, 2 H, H-9/H-9*), 2.81 (s, 3 H, COMe/COMe*), 2.38 (ddd, 1 H, J ₂ _′ _eq,1 _′ = 1.9 Hz, J ₂ _′ _eq,3 _′ = 4.9 Hz and J ₂ _′ _eq,2 _′ _ax = 13.2 Hz, H-2′_eq), 2.34 (ddd, 1 H, J ₂ _′ _eq,1 _′ = 2.0 Hz, J ₂ _′ _eq,3 _′ = 5.2 Hz and J ₂ _′ _eq,2 _′ _ax = 13.2 Hz, H-2′_eq*), 2.16 (s, 3 H, OAc/OAc*), 1.78 (ddd, 1 H, J ₂ _′ _ax,1 _′ = J ₂ _′ _ax,3 _′ = 12.3 Hz and J ₂ _′ _ax,2 _′ _eq = 13.2 Hz, H-2′_ax*), 1.71 (ddd, 1 H, J ₂ _′ _ax,1 _′ = J ₁ _′ _ax,3 _′ = 11.4 Hz and J ₂ _′ _ax,2 _′ _eq = 13.2 Hz, H-2′_ax), 1.28 (d, 3 H_, J ₆ _′ _,5 _′ = 6.1 Hz, H-6′) and 1.26 (d, 3 H, J ₆ _′ _,5 _′ = 6.1 Hz, H-6′*); δ_C (100 MHz, CDCl₃): 203.2, 174.8/174.7*, 170.8, 160.6/160.5*, 156.4*/156.3, 151.0/150.9*, 134.4/134.3*, 129.9*/129.9, 126.8, 121.6, 119.9*/119.8, 113.3*/113.1, 111.8*/111.7, 86.5, 81.5/81.5*, 76.0, 75.7*/75.6, 72.6/72.4*. 64.3*/64.2, 62.2, 54.1, 38.5*/38.5, 36.2, 31.4, 21.6 and 18.6; m/z (EI): 511 (M⁺, 1%), 495(1), 493(1), 467(1), 368(1), 314(1), 256(1) and 149(100).

21

2a,2b: yellow oil; [found (EI): M⁺, 527.1526. C₂₅H₂₅N₃O₁₀ requires: M⁺, 527.1540]; IR(film) cm^-1 3417 (OH), 2982, 2939, 1774 (γ-lactone C=O), 1743 (ester C=O), 1668 (quinone C=O); δ_H (400 MHz, CDCl₃): 7.97 (d, 1 H, J _9,10 = 8.0 Hz, H-9), 7.96 (d, 1 H, J _9,10 = 8.0 Hz, H-9*), 7.93 (d, 1 H, J _10,9 = 8.0 Hz, H-10), 7.92 (d, 1 H, J _10,9 = 8.0 Hz, H-10*), 5.28 (d, 1 H, J _11b,3a = 2.8 Hz, H-11b*), 5.27 (d, 1 H, J _11b,3a = 2.8 Hz, H-11b), 5.13-5.07 (br. m, 1 H, H-1′/H-1′*), 4.91-4.85 (m, 1 H, H-3a/H-3a*), 4.77 (dd, 1 H, J ₄ _′ _,3 _′ = J ₄ _′ _,5 _′ = 9.6 Hz, H-4′), 4.76 (dd, 1 H, J ₄ _′ _,3 _′ = J ₄ _′ _,5 _′ = 9.6 Hz, H-4′*), 3.94 (s, 3 H, OMe), 3.88 (s, 3 H, OMe*), 3.79-3.61 (m, 2 H, H-3′/H-3′* and H-5′/H-5*), 2.95 (dd, 1 H, J _3A,3a = 4.7 Hz and J _3A,3B = 20.2 Hz, H-3A*), 2.95 (dd, 1 H, J _3A,3a = 5.2 Hz and J _3A,3B = 20.3 Hz, H-3A), 2.74 (apparent d, 1 H, J _3B,3A = 20.2 Hz, H-3B*), 2.74 (apparent d, 1 H, J _3B,3A = 20.3 Hz, H-3B), 2.43 (ddd, J ₂ _′ _eq,1 _′ = 2.0 Hz, J ₂ _′ _eq,3 _′ = 4.8 Hz and J ₂ _′ _eq,2 _′ _ax = 13.2 Hz, H-2′_eq*), 2.38 (ddd, J ₂ _′ _eq,1 _′ = 2.0 Hz, J ₂ _′ _eq,3 _′ = 4.9 Hz and J ₂ _′ _eq,2 _′ _ax = 13.2 Hz, H-2′_eq), 2.16 (s, 3 H, OAc/OAc*), 1.80 (s, 3 H, Me/Me*), 1.66-1.54 (m, 1 H, H-2′_ax/H-2′_ax*), 1.29 (d, 3 H, J ₆ _′ _,5 _′ = 6.2 Hz, H-6′) and 1.28 (d, 3 H, J ₆ _′ _,5 _′ = 6.2 Hz, H-6′*); δ_C (100 MHz, CDCl₃): 185.3*/184.6, 183.0/182.6*, 174.9, 170.3, 157.6*/157.5, 148.2, 143.5/143.3*, 133.7/133.5*, 131.1/130.2*, 127.6/127.0*, 124.1, 123.9, 93.9/93.8*, 75.8, 75.7, 72.6*/72.5, 69.3/69.2*, 67.8/67.8*, 63.7/63.5*, 61.9, 38.2/38.1*, 37.2, 28.2/28.1*, 21.5/21.3* and 18.6; m/z (EI): 527 (M⁺, 1%), 467 (M-CH₃CO₂H, 23), 439(8), 311(9), 295(9) and 44 (CH₃CHO⁺, 100).