Glaziovianol, a New Terpenoid Hydroquinone from Auxemma glazioviana Galberto M. da Costa, † Telma L. G. de Lemos,* ,† Otı ´lia D. L. Pessoa, † Francisco J. Q. Monte, † and Raimundo Braz-Filho ‡ Departamento de Quı ´mica Orga ˆ nica e Inorga ˆ nica, Universidade Federal do Ceara ´ , CP 12200 60451-970 Fortaleza, Ceara ´ , Brazil, and Setor de Quı ´mica de Produtos Naturais-LCQUI-CCT, Universidade Estadual do Norte Fluminense, 28015-620 Campos, Rio de Janeiro, Brazil Received December 23, 1998 A novel terpenoid hydroquinone named glaziovianol (1) and three known compounds 6-formyl-2-methoxy- 9-methyl-7,8-dihydro-1,4-phenanthrenedione, ent-19-oxo-16H-kauran-17-oic acid, and rel-8R-hydroxy- 5-hydroxymethyl-2-methoxy-8a-methyl-7,8,8a,9-tetrahydro-1,4-anthracenedione were isolated from the EtOH extract of Auxemma glazioviana wood. The structures were established using spectroscopic analysis (1D and 2D NMR, MS, IR). Previous work with Auxemma oncocalyx allowed the identification of several terpenoid quinones, classified as cordiachromes. 1,2 In continuation of our phytochemical investigation of Auxemma species, a specimen of A. glazio- viana Taub., popularly known as “pau branco louro”, which inhabits mainly the Ceara ´ State, of northeastern Brazil was collected. The wood of this plant, used largely in civil constructions, is resistant to fungi and termite attack. The trunk bark is used in folk medicine for the treatment of cuts and wounds. 3 In this paper we describe the isolation and structure determination of three known compounds: ent-19-oxo- 16H-kauran-17-oic acid, 4 6-formyl-2-methoxy-9-methyl- 7,8-dihydroxy-1,4-phenanthrenedione, and rel-8R-hydroxy- 5-hydroxymethyl-2-methoxy-8a-methyl-7,8,8a,9-tetrahydro- 1,4-anthracendione, 1,2 and a novel terpenoid hydroquinone, glaziovianol (1). Their structures were elucidated based on spectral analysis, including 2D NMR experiments and NOE difference NMR measurements of 1. The diterpene ent-19- oxo-16H-kauran-17-oic acid is reported for the first time in the Boraginaceae family. An ethanol extract of A. glazioviana trunk heartwood was chromatographed over Si gel to yield (1), 6-formyl-2- methoxy-9-methyl-7,8-dihydroxy-1,4-phenanthrenedione, ent- 19-oxo-16H-kauran-17-oic acid, and rel-8R-hydroxy-5- hydroxymethyl-2-methoxy-8a-methyl-7,8,8a,9-tetrahydro- 1,4-anthracenedione. The HBBD- 13 C NMR spectrum of 1 revealed signals corresponding to 16 carbon atoms. Chemi- cal shifts and comparative analysis of HBBD- and DEPT- 13 C NMR spectra were used to recognize the carbon signals as corresponding to one carbonyl, six aromatics, and nine sp 3 : two quaternaries, two methines, four methylenes, and one methyl. The presence of a carbonyl ketone group was also revealed by an absorption at ν max 1699 cm -1 observed in the FT-IR spectrum. The 1 H NMR, HBBD- 13 C NMR and DEPT- 13 C NMR spectra of 1 are consistent with the molecular formula C 16 H 18 O 5 , confirmed by an [M] •+ at m/z 289.9822, in the HREIMS. These data suggest that 1 is a hydroquinone similar to other compounds isolated from Auxemma oncocalyx, 1,2 Cordia elaegnoids, 5 and Cordia alliodora. 6 The presence of two phenolic hydroxyl groups was confirmed by conversion of 1 to the diacetate 2. Hydrogen- carbon direct connectivities of 1 and 2 were determined from a HMQC spectrum. The HMBC spectrum of 1 and 2 revealed coupling between hydrogen and carbon atoms via two ( 2 J CH ) and three ( 3 J CH ) bonds. The p-hydroquinone system was recognized by chemical shifts observed in the 13 C and 1 H NMR spectra of 1. This deduction was confirmed by the HMBC spectrum, indicating interaction of the hydroxyl hydrogen HO-1 with quaternary carbons C-1 and C-9a, and HO-4 with C-4 and C-4a. Subtraction of the p-hydroquinone moiety (C 6 H 4 O 2 ) from the molecular for- mula C 16 H 18 O 5 gives a partial molecular formula C 10 H 14 O 3 for the remaining terpenoid system, containing one car- bonyl, two quaternary, two methine, four methylene, and one methyl carbon atoms, along with a tertiary hydroxyl group observed in the 1 H NMR of 1. The presence of only three oxygen atoms in this moiety and four signals assigned to oxygenated carbons observed in the 13 C NMR spectra of 1 indicated the existence of one ether function. The location of the tetrahydrofuran ring involving the carbon atoms CH- 10, CH-10a, and C-5 was defined from the HMBC spectrum of 2. The heteronuclear long-range interaction between the tertiary methyl carbon CH 3 -12 [1/2: δ C 19.53/18.80 and δ H 0.94 (s)/1.02 (s)] and hydrogens 2H-9 [1/2: δ H , 2.97 (d, J ) 16.5 Hz) and 2.07 (d, J ) 16.5 Hz)/2.96 (d, J ) 16.5 Hz) and 2.27 (d, J ) 16.5 Hz), 3 J CH ] and H-10a [1/2: δ H 2.13 (d, J ) 3.3 Hz)/2.22 (d, J ) 5.4 Hz), 3 J CH ] revealed by HMBC spectra of 1 and 2 were also used to locate the methyl at carbon C-8a (1/2 δ C 41.62/41.68), which also showed coupling with 3H-12 ( 2 J CH , 1 and 2), 2H-9 ( 2 J CH , 2), H-10a ( 2 J CH , 2), 2H-7 ( 3 J CH , 1), and H-10 ( 3 J CH , 1 and 2). The coupling constant values corresponding to vicinal spin-spin interaction [ 3 J H,H ) 3.3 (1) and 5.4 Hz (2)] between hydrogens H-10 [δ H 5.05 (1) and 5.13 (2)] and H-10a [δ H 2.13 (1) and 2.22 (2)] observed in the 1 H NMR spectra of 1 and 2 are consistent with the syn relationship of these hydrogens. The trans B/C ring junction was suggested by the singlet at δ H 0.94 corresponding to a tertiary methyl group (3H-12), whereas the cis-isomer signal appears at δ H 1.05. 7,8 Relative configurations at C-5, C-8a, C-10, and C-10a were assigned based on results obtained by NOE difference spectra: (a) irradiation at δ H 0.94 (3H-12) resulted in 0.7% NOE at δ H 3.86 (H-11R) and 1.0% NOE at δ H 2.97 (H-9); (b) irradiation at δ H 5.05 (H- 10R) showed 4.9% NOE at δ H 2.13 (H-10aR) and 3.5% NOE at δ H 3.86 (H-11R); (c) irradiation at δ H 2.07 (H-9R) revealed 6.6% NOE at δ H 2.97 (H-9) and 2.9% NOE at δ H 2.13 (H- 10aR); (d) irradiation at δ H 3.86 (H-11) resulted in 3.0% * To whom correspondence should be addressed. Tel.: 55-85-2889954. Fax: 55-85-2889782. E-mail: tlemos@dqoi.ufc.br. † Universidade Federal do Ceara ´. ‡ Universidade Estadual do Norte Fluminense. 1044 J. Nat. Prod. 1999, 62, 1044-1045 10.1021/np980575y CCC: $18.00 © 1999 American Chemical Society and American Society of Pharmacognosy Published on Web 06/08/1999