Polyacetylenes from the Roots of Polyalthia debilis Natcha Panthama, Somdej Kanokmedhakul,* and Kwanjai Kanokmedhakul Natural Products Research Unit, Department of Chemistry and Center of Excellence for InnoVation in Chemistry, Faculty of Science, Khon Kaen UniVersity, Khon Kaen 40002, Thailand ReceiVed March 20, 2010 Six new linear polyacetylenic C25 and C27 acetogenins (1-6), named debilisones A-F, have been isolated from a methanol extract of roots of Polyalthia debilis. Structures of these compounds were determined by spectroscopic techniques. The absolute configuration at C-17 of 2 was assigned by the modified Mosher’s method. Compounds 2, 3, and 5 exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis with MIC values of 25.0, 12.5, and 25.0 μg/mL, respectively. Polyalthia debilis (Piere) Finet & ganep (Annonaceae) is a Thai herbal plant growing widely in the northeastern part of Thailand. It is known as “Kon Krok” in Thai, and water decoctions of its roots are used traditionally by the local people for treatment of abdominal pain. 1 Phytochemical investigations on Polyalthia species demonstrated the presence of clerodane diterpenes, 2-4 triterpenes, 5,6 benzopyran derivatives, 7 polyacetylene compounds, 8-11 and azaan- thracene, 12 aporphine, 4,13,14 bisaporphine, 11,15-18 indolesesquiter- pene, 19 seco-benzyltetrahydroisoquinoline, 20 and oxoprotoberberine alkaloids. 4,21 Compounds isolated from the genus Polyalthia have been reviewed. 22 In a previous paper we reported the isolation and characterization of bis-dehydroaporphine alkaloids, bidebilines A-D, from a dichloromethane extract of P. debilis roots. 18 As part of our search for bioactive compounds from Thai plants, a methanol extract of air-dried roots of P. debilis was shown to be active against Mycobacterium tuberculosis (MIC 12.5 μg/mL). This paper de- scribes the isolation, characterization, and bioactivities of six isolated linear C25 (1-5) and C27 (6) acetogenins from the MeOH extract of roots of P. debilis. Results and Discussion Compound 1 was obtained as a white, amorphous solid, and it was assigned the molecular formula C 25 H 40 O 3 from HRESITOFMS, m/z 411.2875 [M + Na] + . The IR spectrum indicated the presence of OH (3461 cm -1 ), conjugated acetylene (2230 cm -1 ), and lactone carbonyl (1769 cm -1 ) groups. The 1 H and 13 C NMR data of 1 (Table 1) were similar to those of linear acetogenins goniothalamusin (7) 23 and oropheolide, 24 except that the side chain of 1 contained a conjugated acetylene group, which was evidenced by signals at δ C 77.5, 66.3, 66.3, and 77.5. 10 The γ-hydroxymethyl-γ-lactone moeity displayed signals at δ H 4.55 (m, H-24), 3.82 (dd, J ) 3.6, 12.4 Hz, H-25a), 3.60 (dd, J ) 4.6, 12.4 Hz, H-25b), and 2.67 (m, H-2) and H 2 -23 protons at δ H 1.95, 2.28 (m). However, the chemical shifts for H-2 and H 2 -23 of 1 differed from those reported for oropheolide [δ H /δ C 2.25 m/32.1 (H-2/C-2) and 2.70 m/39.5 (H-23/C-23)]. 24 The complete interpretation of the NMR data of 1 was established as a result of conclusive DEPT, COSY, HMBC, and NOESY experiments. The specific rotation of 1 (+22.0) was the same sign as its analogue, 7 [+14.6 (c 0.206, CHCl 3 )]. 23 However, there are two closely related γ-lactone acetogenins, oropheolide and saccopetrin A(8), that have the opposite sign of specific rotation [-12 (c 1.0, CHCl 3 ) 24 and -10 (c 0.25, CHCl 3 ), 25 respectively]. Also, the absolute configuration of the γ-lactone ring of 8 was reported as 2R and 24S and proposed to be the enantiomer of 7. 25 The NOESY spectrum of 1 showed a correlation between H-2 and H-24 (Figure 1), suggesting that the two protons are located on the same side of the lactone ring. From the above evidence, the relative configuration * To whom correspondence should be addressed. Tel: +66-43-202222- 41, ext. 12243. Fax: +66-43-202373. E-mail: somdej@kku.ac.th. Figure 1. Selected NOESY correlations of 1. J. Nat. Prod. 2010, 73, 1366–1369 1366 10.1021/np1001913  2010 American Chemical Society and American Society of Pharmacognosy Published on Web 07/13/2010