Phytochemistry, Vol. 20, No. 5, pp. 1159-1161, 1981 hinted in Great Britain. DITERPENOIDS MARDEN A. DE ALVARENGA,~ 0031-9422/81/051159~3 $02.00/O 0 1981 PergamonPress Ltd. FROM zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIH M ICRANDROPSIS SCLEROXYLON* J. JERONIMO DA zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONML SILvA,t HUGO E. GOTTLIEB~ and OTTO R. GoTTLIEBt t Instituto de Quimica, Universidade de S%o Paulo, 05508 S%o Paula, Brazil; $ Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot, Israel (Received 20 M ay 1980) Key zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Word Index--Micrandropis s&roxyLon; Euphorbiaceae; micrandrol-C; 2,6-dihydroxy-7-methyl-l-methylthiophenanthrene; micrandrol-D. Abstract-The structure of micrandrol-C from M icrandropsis scleroxy lon (Euphorbiaceae) is revised to 2,6-dihydroxy7-methyl-1-methylthiophenanthrene. This and other micrandrols are probably diterpenes in view of their co-occurrence with micrandrol-D, the hemiketal of 1,2,3,4,9,10-hexahydro-6-hydroxy-4a-hydroxymethyl-l,l,7-trimethyl-2oxophenanthrene. In previous reports we assigned structures la, lb, 2a, lc and Id respectively to micrandols-A, -B, -C (from M icrandropsis scleroxy lon [2]), -E and -F (from Sagotia racemosa [l]). According to these proposals, micrandrolC is anomalous with respect to the position of one of its hydroxyls at C-8, and indeed Prof. Charles Brown, University of Kent, U.K. has kindly advised us that there are some discrepancies between his ‘H NMR data for synthetic 2,8-dimethoxy-7-methyl-l-methyl-thiophenanthrene (2b ) and the analogous data which we reported for di-0-methylmicrandrol-C [2]. The re-examination of micrandrol-C and its derivatives [2], which thus became advisable, involved analysis of 270 MHz ‘H NMR spectra (Table 1). The low field region of all these spectra showed two pairs of doublets (J = 9 Hz for both) corresponding to two groups of o&o-related protons and two singlets corresponding to two para-related protons. The structure of micrandrolC thus had to be revised to le. Indeed, upon irradiation at the frequencies assigned to H-3, H-4, H-9 and H-10, the doublets of, respectively, H-4, H-3, H-10 and H-9 collapsed into singlets. Furthermore, irradiation at the frequencies of H-4 and of H-S produced NOE enhancements of the H-5 (14 f 2 %) and H-4 (17 f 2%) signals. Finally, irradiation at the frequencies of H-8 and Me-7 resulted in reduction of the widths of halfheight of, respectively, Me-7 (2 to 1 Hz) and H-8 (3 to 1.5 Hz) signals. From the biosynthetic point of view, the micrandrols were tentatively classified as diterpenoids [2]. This hypothesis was firmly established with the isolation, from M icrandropsis scleroxy lon, of micrandrol-D (3). Determination of the constitution of this compound Table H-3 H-4 H-5 H-8 H-9 H-10 Me SMe OAc OAc OMe OMe 1. ‘H NMR (270 MHz) chemical shifts of micrandrol-C (le) and derivatives (If, lg, lh)* le If lg lh 7.31 8.43 7.85 7.63 7.73 8.21 2.45 2.30 - 7.33 8.59 7.86 7.62 7.71 8.50 2.40 2.41 4.08 4.05 7.32 8.71 7.83 7.63 7.73 8.80 2.40 3.13 4.06 4.05 7.37 8.56 8.24 7.76 7.81 8.54 2.39 2.36t 2.41t 2.44t - * Values (6) in ppm from internal Multiplicity Wl/Z J (Hz) (Hz) d 9 d s s d d s s s s s s 9 1.5 2 2 3 2 1.5 2 0.5 0.5 0.5 0.5 0.5 9 9 - TMS for CDCls solutions. t Signals may be interchanged. *Part 3 in the series “The Chemistry of Brazilian Euphorbiaceae”. For Part 2 see ref. [l]. Based on part of the M. SC. thesis presented by J. J. da S., CAPES Fellow, on leave of absence from Universidade Federal de Goias to Universidade de SHo Paulo (1980). involved initially I-IRMS, indicating the molecular formula Cr8HZ403, and ‘H NMR spectroscopy, again pointing unmistakably to the micrandrol-type aromatic ring D. Double irradiation experiments corroborated the proximity of H-14 to both Me-13 and H-7. The presence of an oxy-function at C-3 being biosynthetically justified, nature and localization of the hemiketal bridge resulted from ‘H and i3C NMR evidence. The 0CH2 protons are represented by doublets (6 4.00 and 4.10, J = 9.5 Hz) and the methylene group is hence inserted in a fully substituted carbon; C-3 is represented by a singlet at 6 99.4 and this carbon must hence be fully substituted inclusively by two oxy-functions. Independent corroborative evidence was derived from the study of the ketonic diacetate (v,, 1715 cm- ‘) which resulted in quantitative yield upon treatment of micrandrol-D with AczO and C5H5N at room tempera- 1159 Short Reports 1160 R4 RO R’ R2 R’ R‘+ 9, 10 2a R=H Me la zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA OH H Me tb R=Me Me lb OH H Me dihydro lc Me Me H OMe Me Me Id H OMe dihydro SMe OH H le Me SMe If OMe Me Me SO(Me) OMe Me Me lg SMe lb OAc AC Me o#FoJ$?oJ 15 6 ture. The ‘H and 13C NMR spectra are fully consistent with the expected structure 4, including an unambiguous assignment of A/B tram stereochemistry (cf. models 5 and 6). Carbon chemical shifts were assigned correlating 13C to ‘H signals through residual couplings in sford-spectra. Especially illuminating are the /j- and y-effects exerted by the acetoxyl at C-17 respectively on C-10 (cf. models 5 and 6) and on C-l (cf. 5 and 6) and C-9 (cf. 5) (Table 2). A further instructive difference between the spectra of 4 and 5 refers to the chemical shift values of C-13 and C-14 which reveal respectively p- and y-effects emanating from the isopropyl group methyls of the latter compound (Table 2). An attempt to use analogous ketones [5] as models failed. In our opinion the reported chemical shift values will have to be reassigned. 7 8 The recognition of the 3R,3S,17S absolute stereochemistry of micrandrol-D (3) resulted from the fact that the derived diacetate (4, [ajn - lOSo) and the pair of model compounds hinokione (7, [z]~ + 112” [6]) and totarolone (8, [c(]~ + 102” [7]) give antipodal ORD curves. EXPERIM ENTAL Preparation of la, zyxwvutsrqponm lb and lc by separation of a CHQ extract of Micran- zyxwvu dropsis scleroxy lon has been described [2]. All previously unused fractions were re-chromatographed on a Si gel column, CHCI-Et20 (4:l) eluting a fraction purified by TLC (Si gel, CHCl-Et,O, 1: 1) to 3 (120 mg). Isolation of micrandrol-D. chromatographic Short Reports 1161 Table 2. NMR chemical shifts of micrandrol-D (3), its diacetate (4) and two model compounds (5, 6)* ‘H (270 MHz) 3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 1ZOAc 17-OAc 4 ’ 'C (22.6 MHz) 3 4 5 6 29.2 32.7 38.7 39.7 34.3 33.9 19.ot 34.8 215.4 99.6 41.6 218.3 47.0 35.8 33.3 47.1 48.3 49.9 50.0 54.8 1:; zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 1:; 20.8 19.7 19.l.t 19.6 ca 2.7 m 2.5-2.1 m 30.8 29.5 29.9 33.9 128.7 133.4 132.8 40.4 140.8 146.1 136.7 50.3 40.3 40.0 37.5 36.8 6.69 s 6.90 s 112.7 120.6 117.9 152.9 147.1 148.6 123.2 128.6 136.5 6.82 br. s 6.95 br. s 131.3 131.6 126.6 1.04 s 21.3 21.5 1.17 s 17.9 20.9 1.11 s 1.13 s 27.2 33.2 26.8 26.8 4.00 d (b) 4.24 d (b) 24.7 72.4 66.1 15.8 4.42 d (b) 4.10 dd (c) 2.17 br. s 2.11 br. s 15.5 15.8 27.2 23.0 22.9 2.29 s 20.9 169.5 1.97 s 20.9 171.0 (4 (4 2.2-2.5 m - 2.8-3.1 m - *, i See Table 1. (a)lncluded inafiveproton multiplet B 1.6-1.9 (3)and 1.8-2.1 (4). (b)J = 9.5 (3) and 11.5 (4) Hz. (c)J = 9.5 and 2.5 Hz; small coupling due to W-arrangement with H-l. Dr. Paul M. Baker, NPPN, Universidade Federal do Rio de Micrandrol-D (3), mp 110-120” (CC14-CHCls). [M found: Janeiro, for the HRMS. 288.1719; ClsHs403 requires: 288.1725). v:f; cm-‘: 3425,1621, 1504, 1465, 1269, 1100, 1037, 998, 890.1~~~” nm: 230 inf., 287; ~~:pH*NaoHnm: 242, 300. MS (m/z): 288 (49%) Mt, 258 (43), REFERENCES 232 (lOO),215 (41),201 (17), 187 (21), 185 (17), 174 (35), 173 (53), 172 (34), 171(39), 159 (81). [d]i5 (1.7mg/lOml MeOH) - 108”. 1. Alvarenga, M. A. de, Gottlieb, 0. R. and Magalhftes, M. T. (1976) Phytochemistry 15, 844. ORD (1.7mg/lOml MeOH): [$]sso - 1450, [~]:‘s,, - 4300, 2. Alvarenga, M. A. de and Gottheb, 0. R. (1974) Phytochemistry [#I&, - 3050. CD (1.7mg/lOml MeOH): [9]‘$ - 550. Acetylation of 3 (54mg) in Ac,O (lml) and CsHsN (lml) 13, 1283. 3. Wenkert, E., Buckwalter, B. L., Burfitt, I. R., GaSiC, M. J., (30min, room temp.) gave 4 (78mg), mp 121-123”. v!$.ticm-‘: 1764 (ArOAc), 1742 (ROAc), 1715 (RzCO), 1502, 1462, 1368, Gottlieb, H. E., Hagaman, E. W., Schell, F. M. and Wovkulich, P. M. (1976)in Topics in Carbon-13 NMR Spectroscopy (Levy , 1252, 1208, 1179, 1048,929. MS (m/z): 372 (1%) MC, 330 (lo), G. C., ed.) Vol. 2, p. 95. Wiley, New York. 312 (32), 299 (17), 270 (39), 257 (lOO), 215 (35), 171 (30). [a]:: 4. Majumder, P. L., Maiti, R. N., Panda, S. K., Mal, D., Rajy M. (1.5mg/lOml MeOH) -105”. ORD (l.Smg/lOml MeOH): S. and Wenkert, E. (1979) J. Org. Chem. 44, 2811. [41350- 1750, [4X00- 4050, [+]$r - 950. CD (lSmg/lOml 5. Bohlmann, F. and Czerson, H. (1979) Phytochemistry 18, 115. MeOH): [6]$o - 1200. ORD 7 and 8 respectively zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJ 6. Chow, Y.-L. and Erdtman, H. (1962) Acta Chem. Scand. 16, [+lp02 + 1430 and [4X2 + 1130[61. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 1296. 7. Chow, Y.-L. and Erdtman, H. (1960) Acta Chem. Stand. 14, Acknowledgements-We are indebted to FundacSo de Amparo a 1852. Pesquisa do Estado de S&o Paulo for financial support, and to