Synthesis of Aculeatins A and B via Iterative Hydrolytic Kinetic Resolution

Abstract

A simple and concise approach for the synthesis of aculeatins­ A and B starting from (±)-epichlorohydrin is described. The synthetic strategy features Jacobsen’s hydrolytic kinetic resolution and a Linchpin coupling as key steps.

Key words

hydrolytic kinetic resolution - Linchpin coupling - epoxide­ - spirocyclization - aculeatins

References

• 1a Heilmann J. Mayr S. Brun R. Rali T. Sticher O. Helv. Chim. Acta  2000,  83:  2939 
• 1b Heilmann J. Brun R. Mayr S. Rali T. Sticher O. Phytochemistry  2001,  57:  1281 
• 2 Chin Y.-W. Salim AA. Su B.-N. Mi Q. Chai H.-B. Riswan S. Kardono LBS. Ruskandi A. Farnsworth NR. Swanson SM. Kinghorn AD. J. Nat. Prod.  2008,  71:  390 
• 3 Wong YS. Chem. Commun.  2002,  686 
• 4 Falomir E. Alvarez-Bercedo P. Carda M. Marco JA. Tetrahedron Lett.  2005,  46:  8407 
• 5a Malathong V. Rychnovsky SD. Org. Lett.  2007,  9:  4757 
• 5b Baldwin JE. Adlington RM. Sham VWW. Marquez R. Bulger PG. Tetrahedron  2005,  61:  2353 
• 5c Ramana CV. Pandey SK. Tetrahedron  2010,  66:  390 
• 5d Suresh V. Jon Paul Selvam J. Rajesh K. Venkateswarlu Y. Tetrahedron: Asymmetry  2008,  19:  1509 
• 5e Chandrasekhar S. Rambabu C. Shyamsunder T. Tetrahedron Lett.  2007,  48:  4683 
• 5f Peuchmaur M. Wong YS. J. Org. Chem.  2007,  72:  5374 
• 6a Tamura Y. Yakura T. Haruta JI. Kita Y. J. Org. Chem.  1987,  52:  3927 
• 6b Kaçan M. Koyuncu D. McKillop A. J. Chem. Soc., Perkin Trans. 1  1993,  1771 
• 6c McKillop A. McLaren L. Taylor RJK. J. Chem. Soc., Perkin Trans. 1  1994,  2047 
• 7a Kumar P. Gupta P. Naidu SV. Chem. Eur. J.  2006,  12:  1397 
• 7b Gupta P. Naidu SV. Kumar P. Tetrahedron Lett.  2004,  45:  849 
• 7c Gupta P. Naidu SV. Kumar P. Tetrahedron Lett.  2005,  46:  6571 
• 7d Pandey SK. Kumar P. Tetrahedron Lett.  2005,  46:  6625 
• 7e Kumar P. Naidu SV. J. Org. Chem.  2006,  71:  3935 
• 7f Pandey SK. Kumar P. Synlett  2007,  2894 
• 7g Naidu SV. Kumar P. Tetrahedron Lett.  2007,  48:  3793 
• 7h Gupta P. Kumar P. Eur. J. Org. Chem.  2008,  1195 
• 7i Pandey SK. Pandey M. Kumar P. Tetrahedron Lett.  2008,  49:  3297 
• 8a Tokunaga M. Larrow JF. Kakiuchi F. Jacobsen EN. Science  1997,  277:  936 
• 8b Schaus SE. Brandes BD. Larrow JF. Tokunaga M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc.  2002,  124:  1307 
• 9a Smith AB. Boldi AM. J. Am. Chem. Soc.  1997,  119:  6925 
• 9b Smith AB. Pitram SM. Boldi AM. Gaunt MJ. Sfouggatakis C. Moser WH. J. Am. Chem. Soc.  2003,  125:  14435 
• 9c Smith AB. Boldi AM.
  J. Am. Chem. Soc.  2006,  128:  66 
• For various applications of HKR in syntheses of bioactive compounds, see:
• 10a Kumar P. Naidu SV. Gupta P. Tetrahedron  2007,  63:  2745 
• 10b Kumar P. Gupta P. Synlett  2009,  1367 
• 12a Nicolaou KC. Webber SE. Synthesis  1986,  453 
• 12b Takao K. Ochiai H. Yoshida K. Hashizuka T. Koshimura H. Tadano K. Ogawa S. J. Org. Chem.  1995,  60:  8179 
• 13 Soderquist JA. Miranda EI. Tetrahedron Lett.  1986,  27:  6305 
• 14 McOmie JWF. West DE. Org. Synth. Coll. Vol. V  1973,  412 

11

The enantiomeric purity was determined by converting epoxide 8a into homoallylic alcohol 9 and measuring the optical rotation: [α] _d ^²5 +4.92 (c 1.0, CHCl₃). This value was in good agreement with the literature: [α] _d ^²5 +5 (c 1.0, CHCl₃).^5e