First Synthesis of the Naturally Occurring Diazocarbonyl Compound Cremeomycin

Abstract

The first synthesis of cremeomycin (3-diazo-4-methoxy-2-oxocyclohexa-4,6-dienecarboxylic acid), a naturally occurring diazocarbonyl compound, is described. Starting from methyl 2-hydroxy-4-methoxybenzoate, nitration, hydrolysis, and reduction gave 3-amino-2-hydroxy-4-methoxybenzoic acid as the key aminophenol precursor, diazotization of which gave the diazoquinone natural product.

natural products - total synthesis - diazo compounds - electrophilic aromatic substitution

References

1 Doyle MP. McKervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds   Wiley; New York: 1998. 

2 Bartz QR. Haskell TH. Elder CC. Johannessen DW. Frohardt RP. Ryder A. Fusari SA. Nature  1954,  173:  72 

3 Fusari SA. Frohardt RP. Ryder A. Haskell TH. Johannessen DW. Elder CC. Bartz QR. J. Am. Chem. Soc.  1954,  76:  2878 

4 Fusari SA. Haskell TH. Frohardt RP. Bartz QR. J. Am. Chem. Soc.  1954,  76:  2881 

5 Ehrlich J. Coffey GL. Fisher MW. Hillegas AB. Kohberger DL. Machamer HE. Rightsel WA. Roegner FR. Antibiot. Chemother.  1956,  6:  487 

6 Dion HW. Fusari SA. Jakubowski ZL. Zora JG. Bartz QR. J. Am. Chem. Soc.  1956,  78:  3075 

7 DeVoe SE. Rigler NE. Shay AJ. Martin JH. Boyd TC. Backus EJ. Mowat JH. Bohonos N. Antibiot. Ann.  1956-1957,  730 

8 Patterson EL. Johnson BL. DeVoe SE. Bohonos N. Antimicrob. Agents Chemother.  1965,  115 

9 Rao KV. Brooks SC. Kugelman M. Romano AA. Antibiot. Ann.  1959-1960,  943 

10 Rao KV. Antimicrob. Agents Chemother.  1961,  178. 

11 Rao KV. Antimicrob. Agents Chemother.  1962,  179 

12 Lee MD. Fantini AA. Kuck NA. Greenstein M. Testa RT. Borders DB. J. Antibiot.  1987,  40:  1657 

13 Kameyama T. Takahashi A. Matsumoto H. Kurasawa S. Hamada M. Okami Y. Ishizuka M. Takeuchi T. J. Antibiot.  1988,  41:  1561 

14 Takahashi A. Nakamura H. Ikeda D. Naganawa H. Kameyama T. Kurasawa S. Okami Y. Takeuchi T. Iitaka Y. J. Antibiot.  1988,  41:  1568 

15 Nishimura M. Nakada H. Nakajima H. Hori Y. Ezaki M. Goto T. Okuhara M. J. Antibiot.  1989,  42:  542 

16 Nishimura M. Nakada H. Takase S. Katayama A. Goto T. Tanaka H. Hashimoto M. J. Antibiot.  1989,  42:  549 

17 Singh PD. Johnson JH. Aklonis CA. O’Sullivan J. J. Antibiot.  1986,  39:  1054 

18 Nihei Y. Hasagawa M. Suzuki K. Yamamoto S. Hanada M. Furumai T. Fukagawa Y. Oki T. J. Antibiot.  1993,  46:  900 

19 Imae K. Nihei Y. Oka M. Yamasaki T. Konishi M. Oki T. J. Antibiot.  1993,  46:  1031 

20 Bergy ME, and Pyke TR. inventors; US Patent  3350269.  ; Chem. Abstr. 1968, 68, 20924

21 McGuire JN. Wilson SR. Rinehart KL. J. Antibiot.  1995,  48:  516 

22 Griesbeck AG. Zimmermann E. In Science of Synthesis   Vol. 28:  Griesbeck AG. Thieme; Stuttgart: 2006.  p.807-830  

23 Heretsch P. Giannis A. Synthesis  2007,  2614 

24 Jadhav GV. Deshpande VN. J. Indian Chem. Soc.  1952,  29:  773 

25 Cox PJ, Bower S, Aldous DJ, Astles PC, McGarry DG, Hulme C, Regan JR, Huang F.-C, Djuric SW, Moriarty KJ, Mathew RM, and Poli GB. inventors; Patent  WO9748697.  ; Chem. Abstr. 1998, 128, 102087