Total Synthesis of (+)-Aspicilin from d-Mannitol

Abstract

The total synthesis of the 18-membered lichen macrolide, (+)-aspicilin, has been accomplished utilizing the Swern oxidation, Masamune-Roush olefination, and ring-closing metathesis of a trienic ester as key steps. d-Mannitol has been utilized as the chiral pool material for the construction of the olefinic aldehyde and the Jacobsen hydrolytic kinetic resolution has been employed for the construction of the olefinic phosphonate ester.

Key words

(+)-aspicilin - Swern - Masamune-Roush olefination - ring-closing metathesis - d-mannitol - kinetic resolution

References and Notes

• 1a Hesse O. J. Prakt. Chem.  1900,  62:  430 
• 1b Hesse O. J. Prakt. Chem.  1904,  70:  449 
• 2 Huneck S. Schreiber K. Steglich W. Tetrahedron  1973,  29:  3687 
• 3 Quinkert G. Heim N. Bats JW. Oshkinat H. Kessler H. Angew. Chem., Int. Ed. Engl.  1985,  24:  987 
• 4a Banwell MG. Mcrae K. J. Org. Lett.  2000,  2:  3583 
• 4b Maezaki N. Li Y.-X. Ohkubo K. Goda S. Iwata C. Tanaka T. Tetrahedron  2000,  56:  4405 
• 4c Dixon DJ. Foster AC. Ley SV. Org. Lett.  2000,  2:  123 
• 4d Kobayashi Y. Nakano M. Kumar GB. Kishihara K. J. Org. Chem.  1998,  63:  7505 
• 4e Nishioka T. Iwabuchi Y. Irie H. Hatakeyama S. Tetrahedron Lett.  1998,  39:  5597 
• 4f Chenevert R. Lavoie M. Dasser M. Can. J. Chem.  1997,  75:  68 
• 4g Sinha SC. Keinan E. J. Org. Chem.  1997,  62:  377 
• 4h Enders D. Prokopenko OF. Liebigs Ann.  1995,  1185 
• 4i Oppolzer W. Radinov RN. de Brabander J. Tetrahedron Lett.  1995,  36:  2607 
• 4j Solladie G. Fernandez I. Maestro C. Tetrahedron: Asymmetry  1991,  2:  801 
• 4k Quinkert G. Becker H. Durner G. Tetrahedron Lett.  1991,  32:  7397 
• 4l Quinkert G. Fernholz E. Eckes P. Durner G. Helv. Chim. Acta  1989,  72:  1753 
• 4m Quinkert G. Heim N. Glenneberg J. Doller U. Eichhorn M. Billhardt U.-M. Schwarz C. Zimmerman G. Bats JW. Durner G. Helv. Chim. Acta  1988,  71:  1719 
• 4n Waanders PP. Thijs L. Zwanenburg B. Tetrahedron Lett.  1987,  28:  2409 
• 4o Raghavan S. Sreekanth T. Tetrahedron Lett.  2006,  47:  5595 
• 5 Chakraborty TK. Ghosh S. Rao MHVR. Kunwar AC. Cho H. Ghosh AK. Tetrahedron Lett.  2000,  41:  10121 
• 6 Garegg PG. Samuclson B. Synthesis  1979,  813 
• 7 Tolstikov GA. Miftakhov MS. Vostrikov NS. Komissarova NG. Adler ME. Kuznetsov OM. Zh. Org. Khim.  1988,  24:  224 ; Chem. Abstr. 1989, 110, 7162
• 8 Tolstikov GA. Miiftakhov MS. Alder ME. Komissarova NG. Kuznetsov OM. Vostrikov NS. Synthesis  1989,  940 
• 9a Tokunaga M. Larrow JF. Kakiuchi F. Jacobsen EN. Science  1997,  277:  936 
• 9b Schaus SE. Brandes BD. Larrow JF. Tokunaga M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc.  2002,  124:  1307 
• 9c

  The epoxide 12 was analysed by chiral HPLC using Chiralcel IC column with a flow rate of 1.0 mL/min and solvent system of 3% i-PrOH-hexane. The ee was determined to be >98%.

• 10 Banwell MG. McRae KJ. Org. Lett.  2000,  2:  3583 
• 11 Blanchette MA. Choy W. Davis JT. Essenfeld AP. Masamune S. Roush WR. Sakai T. Tetrahedron Lett.  1984,  25:  2183 
• 12 Trnka TM. Grubbs RH. Acc. Chem. Res.  2001,  34:  18 
• 13 Nishioka T. Iwabuchi Y. Irie H. Hatakeyama S. Tetrahedron Lett.  1998,  39:  5597 

14

Experimental procedures and spectral data for selected compounds are given in the Supporting Information.