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Synlett 2008(14): 2101-2102  
DOI: 10.1055/s-2008-1078250
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Ptaeroxylin (Desoxykarenin): An Unusual Chromone from the Sneezewood Tree Ptaeroxylon obliquum

Marina Muscarellaa,b, Marc C. Kimbera, Christopher J. Moody*a
a School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
Fax: +44(115)9513564; e-Mail: c.j.moody@nottingham.ac.uk;
b Dipartimento Farmacochimico Tossicologico e Biologico, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy
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Publication History

Received 3 July 2008
Publication Date:
05 August 2008 (online)

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Abstract

The first synthesis of the oxepinochromone ptaeroxylin (also known as desoxykarenin) isolated from the sneezewood tree is described, in which the key steps are a Claisen rearrangement and a ring-closing metathesis to form the seven-membered oxygen heterocyclic ring.

Keywords

natural products - chromones - Claisen rearrangement - ring-closing metathesis reaction

    References and Notes

  • 1 Dean FM. Taylor DAH. J. Chem. Soc. C  1966,  114 
  • 2 McCabe PH. McCrindle R. Murray RDH. J. Chem. Soc. C  1967,  145 
    Crossref
  • 3 Dean FM. Parton B. Somvichien N. Taylor DAH. Tetrahedron Lett.  1967,  3459 
  • 4 Brown RT. Blackstock WP. Chapple CL. J. Chem. Soc., Perkin Trans. 1  1975,  1776 
    Crossref
  • 5 Rehder KS. Kepler JA. Synth. Commun.  1996,  26:  4005 
    CrossrefSearch in Google Scholar
  • 7a Stefinovic M. Snieckus V. J. Org. Chem.  1998,  63:  2808 
    Search in Google Scholar
  • 7b Chattopadhyay SK. Dey R. Biswas S. Synthesis  2005,  403 
  • 7c Rotzoll S. Görls H. Langer P. Synthesis  2008,  45 
6

Synthesis of 6-Allyl-5,7-dihydroxy-2-methyl-4 H -chromen-4-one ( 11)
5-Allyloxy-7-hydroxy-2-methyl-4H-chromen-4-one (8, 0.15 g, 0.65 mmol) was heated in N,N-dimethylaniline (1.5 mL) and Ac2O (1.5 mL) at 200 ˚C for 1.5 h in a microwave reactor (300 W). The mixture was poured into HCl (6 M, 40 mL) and then extracted with EtOAc (3 × 30 mL). Chromatography (CH2Cl2-EtOAc, 95:5) gave a mixture of 6-allyl-5-hydroxy-2-methyl-4-oxo-4H-chromen-7-yl acetate (9, 0.06 g, 34%) and 6-allyl-2-methyl-4-oxo-4H-chromene-5,7-yl diacetate (10, 0.12 g, 58%).
To the above mixture (0.13 g) was added a solution of K2CO3 (0.15 g) in MeOH (2.5 mL). The solution was heated under reflux for 30 min. The solvent was removed in vacuo and H2O (10 mL) was added. The solution was then acidified with HCl (6 M) and the resulting solid filtered to give the title compound 11 as a colourless solid (0.09 g, 87%); mp 232-234 ˚C. HRMS: m/z calcd for C13H13O4: 233.0808; found [MH+]: 233.0811. IR (CHCl3): νmax = 3007, 1657, 1634, 1587, 1456, 1152 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 13.08 (1 H, s, OH), 10.78 (1 H, s, OH), 6.40 (1 H, s, H-8), 6.15 (1 H, s, H-3), 5.91-5.81 (1 H, m, =CH), 4.96-4.90 (2 H, m, =CH2), 3.25 (2 H, d, J = 6.0 Hz, CH2), 2.33 (3 H, s, Me). ¹³C NMR (100 MHz; CDCl3): δ = 183.3 (C), 167.9 (C), 162.3 (C), 159.1 (C), 156.2 (C), 136.1 (CH), 115.1 (CH2), 109.3 (C), 108.3 (CH), 103.6 (C), 93.4 (CH), 26.4 (CH2), 20.3 (Me).

8

Synthesis of 5-Hydroxy-6,9-dihydro-2,8-dimethyl-4 H -oxepino[3,2- g ]chromen-4-one (Ptaeroxylin, 2) A solution of 6-allyl-5-hydroxy-2-methyl-7-[(2-methyl-prop-2-en-1-yl)oxy]-4H-chromen-4-one (12, 0.035 g, 0.135 mmol) in CH2Cl2 (65 mL, 0.002M) was treated with a single portion (0.021 g, 20 mol%) of bis(tricyclohexylphosphine)benzylidene ruthenium(IV) dichloride. The solution was heated under reflux for 18 h. The solvent was removed in vacuo and the brown residue filtered through a short pad of Celite using cyclohexane-EtOAc (9:1) as eluent. The solvent was then removed and the residue purified by chromatography (cyclohexane-EtOAc, 9:1) to give the title compound 2 as a colourless solid (0.020g, 64%); for analytical data, see ref. 9.

9
(9) Table 1 Comparison of Data for Natural and Synthetic Ptaeroxylin
Natural product
(ref. [¹] ) 		Natural product
(ref. [²] ) 		Synthetic ­sample
Mp 135-138 ˚C 133-135 ˚C 126-128 ˚C
¹H NMR CDCl3 CDCl3 CDCl3
OH 13.02 (1 H, s)
H-11 6.51 (1 H, s) 6.56 (1 H, s)
H-3 6.01 (1 H, s) 6.06 (1 H, s)
H-7 5.6 (1 H, t) 5.67 (1 H, t,
J = 6 Hz) 		5.73-5.70 (1 H, br t, J = 4.4 Hz)
H-9 4.4 (2 H, s) 4.53 (2 H, s) 4.53 (2 H, s)
H-6 3.4 (2 H, m) 3.48 (2 H, d,
J = 6 Hz) 		3.60 (2 H, d, J = 4.4 Hz)
2-Me 2.34 (3 H, s) 2.37 (3 H, s)
8-Me 1.54 (3 H, s) 1.60 (3 H, s) 1.62 (3 H, s)
IR Nujol (cm-¹) CHCl3 (cm-¹) CHCl3 (cm-¹)
ca. 2970 3011
1650 1656 1655
1610 1627 1626
1590 1595 1592
UV EtOH (nm) EtOH (nm) MeCN (nm)
206 (log ε 4.20) 209 (log ε 4.23)
230 (log ε 4.17) 232 (log ε 4.27) 232 (log ε 4.2)
241 (log ε 4.22)
255 (log ε 4.15) 255 (log ε 4.24) 254 (log ε 4.1)
284 (log ε 3.68)
320 (log ε 2.60) 321 (log ε 3.59) 322 (log ε 3.5)