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

Marina Muscarella; Marc C. Kimber; Christopher J. Moody

doi:10.1055/s-2008-1078250

LETTER

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

Marina Muscarella^a,b, Marc C. Kimber^a, 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

Abstract

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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

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References

References and Notes

<A NAME="RD25208ST-1">1</A> Dean FM. Taylor DAH. J. Chem. Soc. C 1966, 114

<A NAME="RD25208ST-2">2</A> McCabe PH. McCrindle R. Murray RDH. J. Chem. Soc. C 1967, 145

<A NAME="RD25208ST-3">3</A> Dean FM. Parton B. Somvichien N. Taylor DAH. Tetrahedron Lett. 1967, 3459

<A NAME="RD25208ST-4">4</A> Brown RT. Blackstock WP. Chapple CL. J. Chem. Soc., Perkin Trans. 1 1975, 1776

<A NAME="RD25208ST-5">5</A> Rehder KS. Kepler JA. Synth. Commun. 1996, 26: 4005

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): ν_max = 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).

<A NAME="RD25208ST-7A">7a</A> Stefinovic M. Snieckus V. J. Org. Chem. 1998, 63: 2808

<A NAME="RD25208ST-7B">7b</A> Chattopadhyay SK. Dey R. Biswas S. Synthesis 2005, 403

<A NAME="RD25208ST-7C">7c</A> Rotzoll S. Görls H. Langer P. Synthesis 2008, 45

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) Table 1 Comparison of Data for Natural and Synthetic Ptaeroxylin

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