First Stereoselective Total Synthesis of Sporostatin and Determination of Absolute Configuration

Abstract

The first simple and efficient total synthesis of sporostatin has been accomplished in five steps starting from (S)-propylene oxide. The synthesis utilizes simple reactions such as esterification, cross-metathesis, and intramolecular Friedel-Crafts reaction as key steps.

Key words

homoallyl alcohol - cross-metathesis - intramolecular Friedel-Crafts reaction

References and Notes

• 1a Murakami Y. Ishii A. Mizuno S. Yaginuma S. Uehera Y. Anticancer Res.  1999,  19:  4145 
• 1b Kinoshita K. Sasaki T. Awata M. Takada M. Yaginuma S.
  J. Antibiot.  1997,  50:  961 
• 2a Edarada RA. Heubes M. Brauers G. Wary V. Berg A. Grafe G. Proksch P. J. Nat. Prod.  2002,  65:  1598 
• 2b Musgrave OC. J. Chem. Soc.  1956,  4301 
• 2c Lai S. Shozuri Y. Yamamura S. Kawai K. Terada Y. Furukuwa H. Tetrahedron Lett.  1989,  30:  2241 
• 2d Robeson DJ. Strobel GA. Strange RN. J. Nat. Prod.  1985,  48:  139 
• 2e Ghisalberti EL. Rowland CY. J. Nat. Prod.  1993,  56:  2175 
• 3a Bringmann G. Lang G. Michel M. Heubes M. Tetrahedron Lett.  2004,  45:  2829 
• 3b Yoshino T. Ng F. Danishefsky SJ. J. Am. Chem. Soc.  2006,  128:  14185 
• 3c Liang Q. Zhang J. Quan W. Sun Y. She X. Pan X. J. Org. Chem.  2007,  72:  2694 
• 4 Bonini C. Chiummiento L. Lopardo MT. Pullex M. Colobert F. Solladie G. Tetrahedron Lett.  2003,  44:  2695 
• 5 Furrow ME. Schaus SE. Jacobsen EN. J. Org. Chem.  1998,  68:  6776 
• 6 Kumar P. Gupta P. Naidu V. Chem. Eur. J.  2006,  12:  1397 
• 7a BouzBouz S. Cossy J. Tetrahedron Lett.  2006,  47:  901 
• 7b Garber S. Kingsbury JS. Gray BL. Hoveyda AH. J. Am. Chem. Soc.  2002,  122:  8168 
• 7c Gessler S. Randl S. Blechert S. Tetrahedron Lett.  2004,  41:  9973 
• 7d Wakematsu H. Blechert S. Angew. Chem. Int. Ed.  2002,  41:  2403 
• 7e Kitamura T. Sato Y. Mori M. Tetrahedron  2004,  60:  9649 
• 7f Cossy J. Bargiggia F. BouzBouz S. Org. Lett.  2003,  459 
• 7g Kingsbury JS. Harrity JPA. Bonitatebus PJ. Hoveyda AH. J. Am. Chem. Soc.  1999,  121:  791 
• 7h Hoffmann TJ. Rigby JH. Arseniyadis S. Cossy J. J. Org. Chem.  2008,  73:  2400 
• 8 Bracher F. Schulte B. Liebigs Ann./Recl.  1997,  1979 
• 9a Kreipl PT. Reid C. Steglich W. Org. Lett.  2002,  4:  3287 
• 9b Konwar D. Boruah RC. Sandhu JS. Tetrahedron Lett.  1990,  31:  1063 
• 10a Reddy MVR. Yucel AJ. Ramachandran PV.
  J. Org. Chem.  2001,  66:  2512 
• 10b Kumar P. Gupta P. Naidu SV. Chem. Eur. J.  2006,  12:  1397 
• 10c Yadav JS. Niranjan Kumar N. Reddy MS. Prasad AR. Tetrahedron  2007,  12:  2689 

11

( S )-1,3-Dihydroxy-8-methyl-8,9-dihydro-5 H -7-oxa-benzocyclodecene-6,12-dione (Sporostatin, 1)
Iodine (0.52 g, 2.06 mmol) was added to a mixture of aluminum (0.074 g, 2.76 mmol) in dry benzene. The mixture was refluxed for 1 h, cooled to r.t., and then n-Bu4N⁺I^- (0.0032 g, 0.0089 mmol) and compound 10 (0.020 g, 0.688 mmol) in dry benzene (8 mL) were added. The mixture was stirred for 45 min at 10 ˚C and quenched with H₂O. After acidification with 2 M HCl, the mixture was extracted with EtOAc (3 × 10 mL). The organic phase was washed with brine, dried over Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on SiO₂ (hexanes-EtOAc, 1:1) to afford the sporostatin (1, 0.017 mg, 95%) as white solid, mp 198-200 ˚C; [α]_D ^²5 -18.8 (c 0.5, MeOH). ^¹H NMR (300 MHz, DMSO): δ = 13.59 (s, 1 H), 10.75 (s, 1 H), 6.80 (d, 1 H, J = 15.8 Hz), 6.32 (s, 1 H), 6.22 (s, 1 H), 5.92-5.98 (m, 1 H), 5.01-5.11 (m, 1 H), 4.07 (d, 1 H, J = 16.8 Hz), 3.82-3.90 (m, 1 H), 2.54-2.58 (m, 1 H), 1.36 (d, 3 H, J = 6.5 Hz). ^¹³C NMR (75 MHz, DMSO):
δ = 198, 173.1, 167.4, 163.7, 140.0, 138.2, 136.3, 114.5, 111.7, 102.1, 74.9, 43.9, 41.6, 19.6. IR (neat): ν = 3424, 2255, 2128, 1739, 1650, 1376 cm^-¹. MS (LC-MS): m/z = 263 [M + 1]⁺. HRMS: m/z calcd for C₁₄H₁₅O₄: 263.0919; found: 263.0916.