Concise Synthesis of (±)-Smenochromene D (= Likonide B)

Abstract

The total synthesis of smenochromene D, an unusual ansa-terpenoid is described. The synthesis features an unprecedented macrocyclization proceeding through a biomimetic electrocyclization. The enantiomeric relationship between smenochromene D and likonide B is established.

smenochromenes - likonides - chromenes - macrocycli­zation - ansa-compounds - ortho-quinone methides

References

1 Clardy J. Faulkner DJ. Venkateswarlu Y. Rios Steiner JL. Corcoran E. J. Org. Chem.  1991,  56:  6271 

2 Kashman Y. Rudi A. Benayahu Y. Org. Lett.  2004,  6:  4013 

3 For a comprehensive review on the chemistry of ortho-quinone methides, see: Van de Water RW. Pettus TRR. Tetrahedron  2002,  58:  5367 

4 Umbreit MA. Sharpless KB. J. Am. Chem. Soc.  1977,  99:  5526 

5 Banwell MG. Flynn BL. Stewart SG. J. Org. Chem.  1998,  63:  9139 

6 Parikh JR. von Doering WE. J. Am. Chem. Soc.  1967,  89:  5505 

7a Snieckus V. Chauder BA. Lopes CC. Lopes RSC. da Silva AJM. Synthesis  1998,  279 

7b Murphy WS. Tuladhar SM. Duffy B. J. Chem. Soc., Perkin Trans. 1  1992,  605 

7c Bissada S. Lau CK. Bernstein MA. Dufresne C. Can. J. Chem.  1994,  72:  1866 

8

Experimental Procedure. To a solution of 10 (20.0 mg, 0.0558 mmol) in toluene (4 mL) was added phenylboronic acid (14.0 mg, 0.0837 mmol) and HOAc 0.400 mL. The reaction mixture was then fitted with a Dean Stark apparatus and heated at reflux for 3 h. The mixture was cooled to r.t., diluted with CH₂Cl₂, washed with H₂O, sat. NaHCO₃, and brine, dried over MgSO₄, and concentrated in vacuo. The product was purified by column chromatography (10% EtOAc in hexane) to afford 4.9 mg (26%) of smenochromene D as a clear oil. R _f = 0.26 (10% EtOAc in hexane, CAM). IR: 3394, 2921, 2852, 1616, 1505 cm^-1. ¹H NMR: (500 MHz): δ = 6.52 (s, 1 H), 6.31 (d, J = 12.8 Hz, 1 H), 6.29 (s, 1 H), 5.31 (d, J = 12.8 Hz, 1 H), 4.93 (t, J = 7.2 Hz, 1 H), 4.82 (t, J = 8, 1 H), 4.52 (d, J = 15.2 Hz, 1 H), 4.14 (d, J = 15.2 Hz, 1 H), 3.76 (s, 3 H), 2.09 (m, 4 H), 1.77 (m, 2 H), 1.69 (s, 3 H), 1.58 (m, 2 H), 1.47, (s, 3 H), 1.36 (s, 3 H). ¹³C NMR (500 MHz): δ = 153.4, 150.3, 139.3, 132.0, 131.8, 129.8, 126.6, 125.8, 123.5, 119.1, 113.3, 99.9, 80.3, 79.0, 55.6, 41.4, 38.9, 30.2, 24.6, 23.1, 14.4, 14.1. HRMS: m/z calcd for C₂₂H₂₈0₃ [M⁺]: 340.2038; found: 340.2033.

9 Nagata W. Okada K. Synthesis  1979,  365