Synthesis of Acetomycin Bislactone Analogues

Abstract

Bislactones 5 and 6 have been designed as esterase-resistant acetomycin analogues and prepared in 10 steps from methyl 2-methylacetoacetate. Consecutive quaternary and tertiary carbon centers at the C-3 and C-4 positions on the γ-lactone ring are constructed by Pd-catalyzed allylic alkylation in one step. The relative stereochemistry for 6 has been determined by X-ray crystallographic analysis.

bioorganic chemistry - palladium - esterase - stereoselective synthesis - γ-lactone

References

1 Ettlinger L. Gaumann E. Hutter R. Schierlein WK. Kradolfer F. Neipp L. Prelog V. Zahner H. Helv. Chim. Acta  1958,  41:  216 

2 Uhr H. Zeeck A. J. Antibiot.  1985,  38:  1684 

3 Cano FH. Foces C. Acta Crystallogr.  1988,  C44:  919 

4a Alarcon B. Lacal JC. Sousa JMF. Carrasco L. Antiviral Res.  1984,  4:  231 

4b Chen Y. Zeeck A. Chen Z. Zahner H. Kangsnengsu  1984,  9:  16 

5 Mamber SW. Mitulski JD. Hamelehle KL. French JC. Hokanson GC. Shillis JL. Leopold WR. Von Hoff DD. Tunac JB. J. Antibiot.  1987,  40:  73 

6 Mamber SW. Mitulski JD. Borondy PE. Tunac JB. J. Antibiot.  1987,  40:  77 

7 Uenishi J. Kobayashi N. Komine S. Okadai T. Yonemitsu O. Sasaki T. Yamada Y. Chem. Pharm. Bull.  1999,  47:  517 

8 Uenishi J. Kobayashi N. Yonemitsu O. Sasaki T. Yamada Y. Heterocycles  1997,  44:  277 

9 Uenishi J. Adv. Pharm. Sci.  1999,  15:  1 

10 Uenishi J. Kawatsura M. Ikeda D. Muraoka N. Eur. J. Org. Chem.  2003,  20:  3909 

11 Qin D.-G. Zha H.-Y. Yao Z.-J. J. Org. Chem.  2002,  67:  1038 

12 Kozikowski AP. J. Org. Chem.  1984,  49:  2301 

13 Node M. Kumar K. Nishide K. Ohsugi S. Miyamoto T. Tetrahedron Lett.  2001,  42:  9207