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

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 
• 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 
• 5 Rehder KS. Kepler JA. Synth. Commun.  1996,  26:  4005 
• 7a Stefinovic M. Snieckus V. J. Org. Chem.  1998,  63:  2808 
• 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): 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).

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)