Pergamon 0031-9422(94)00583-4 Phytochemistry, Vol. 38, No. 1, pp. 189 194, 1995 Copyright © 1995 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0031-9422/95 $9.50 + 0.00 CLERODANE AND ENT-HALIMANE DITERPENES FROM POLYALTHIA LONGIFOLIA NORIYUKI HARA, HITOMI ASAKI, YOSHINORI FUJIMOTO,* YOGESH KUMAR GUPTA,~ ASHISH KUMAR SINGH~ and MAHENDRASAHAI~ Department of Chemistry, Tokyo Institute of Technology, Meguro, Tokyo 152,Japan; 1"Department of Medicinal Chemistry, I.M.S., Banaras Hindu University, Varanasi 221005, India (Received 6 June 1994) Key Word lndex--Polyalthia longifolia; Annonaceae; clerodane; ent-halimane; bicyclic diterpene. Abstract--A hexane extract of the stem bark of Polyalthia longifolia furnished nine new clerodane and ent-halimane diterpenes, i.e. 16-hydroxycleroda-4(18),13-dien-16,15-olide, 16-oxocleroda-4(18),13E-dien-15-oic acid, cleroda-4(18),- 13-dien-16,15-olide, 16-hydro xy-ent-halima- 5( l O),13-dien-16,15-olide, 16-o x o-ent-halima- 5( l O),13 E-dien-15-oic acid, ent-halima- l ( l O),13 E-dien-16,15-olide, 16-o x o-ent-halima- 5(l O),13 E-dien-15-oic acid, ent-halima- 5( l O),13-dien-16,15- olide and ent-halima-5(lO),13E-dien-16,15-olide, along with five known clerodane diterpenes. The structures of these compounds were elucidated by Sl~Ctrosc~pic methods. The 13E configuration of two of the new ent-halimanes and one of the known clerodanes was firmly established by NOE experiments. INTRODUCTION Annonaceae plants are a rich source of bioactive sub- stances [ 1 ] and certain genera of this family have recently attracted much interest, since they contain a group of antitumour active tetrahydrofuranic acetogenins [2]. In a continuation of our studies on annonaceous plants, we examined a hexane extract of the stem bark of Polyalthia longifolia Thw. Polyalthia longifolia is widely distributed in India and commonly known as Asoka in Hindi. Aporphine and azafluorene alkaloids [3, 4,l, proantho- cyanidines [5,l, and clerodane diterpenes [6-8] have been isolated from the plant. In this paper, we describe the isolation and the structure elucidation of three new clerodanes (2, 9 and 12) and six new ent-halimanes [(10 ~ 9)-friedolabdanes,l (3, 6, 7, 10, 13 and 14), along with five known clerodane diterpenes (1, 4, 5, 8 and 11). RESULTSAND DISCUSSION The stem bark of P. longifolia was extracted with hexane. Separation of the extract by silica gel chromato- graphy with hexane-ethyl acetate and ethyl acetate- methanol as eluents afforded three major fractions, A (0.49% based on bark), B (2.3%) and C (0.96%), and one minor fraction, D (0.07%). Further reversed-phase HPLC separation of these fractions furnished I-3 from fraction A, 4-7 from fraction B, 8-10 from fraction C, and 11-14 from fraction D. Compounds 1-7 and 11-14 were isol- ated in a pure state, while 8-10 were obtained in ca 90% *Author to whom correspondence should be addressed. purity due to the failure to obtain base line separation of these compounds in HPLC. Compound 1, C2oH3oO3, (ELMS m/z 318 [Ml+), was identified as 16-hydroxycleroda-3,13-dien-16,15-olide by comparing the NMR data (Tables 1 and 2) with those reported in the literature [6, 7, 9]. The NMR data further indicated that 1 is a 1 : 1 epimeric mixture at C-16. This compound was previously isolated from the same species [6, 7,l, P. viridis [9, 10,l and Acritopappus longifolius [11,l. It is interesting to note that the 16S configuration was assigned to the compound isolated from the leaves [6,l and the stem bark [7] of P. longifolia, whereas the 16R configuration was assigned to the compound isolated from P. viridis [9]. Recently, the compound isolated from Premna oligotricha was reported to be a 17: 3 mixture of the C-16 epimers [12,l. We found that the (R)-MTPA esters of the 16R- and 16S-epimers were readily separable on silica gel TLC, although the C-16 configuration of the separated epimers has not yet been assigned (~H NMR R R R R 3 18 18 18 19 18 19 1 : R=A 2 : R=A 3 : R=A 7 : R=B 4 : R=B 5 : R=B 6 : R=B 14 : R=D 8:R=C 9:R=C 10: R--C 11 :R=D 12 : R=D 13 : R=D ~s ~ 0 , :' ,: OH ~ 189