《有机化学》课程教学资源（参考书籍）Nature pruduct commucations，An International Journal for Communications and Reviews Covering all Aspects of Natural Products Research，Pawan K. Agrawal.pdf_P6-P10

Natural Product Communications 2006 Volume 1, NUMBER 12 Contents Original paper Page Triterpenes from Maytenus macrocarpa and Evaluation of Their Anti-HIV activity Sonia Piacente, Lourdes Campaner Dos Santos, Naheed Mahmood and Cosimo Pizza 1073 New Oxidized 4-Oxo Fatty Acids from Hygrophorus discoxanthus Gianluca Gilardoni, Marco Clericuzio, Alberto Marchetti, Paola Vita Finzi, Giuseppe Zanoni and Giovanni Vidari 1079 Kenyaloside, a Novel O,O,O-Triglycosylated Naphthalene Derivative from the Exudate of Kenyan Aloe Species Giovanna Speranza, Daniela Monti, Sergio Crippa, Paola Cairoli, Carlo F. Morelli and Paolo Manitto 1085 New Flavonoid Glycosides from Chrozophora senegalensis and Their Antioxidant Activity Antonio Vassallo, Giuseppina Cioffi, Francesco De Simone, Alessandra Braca, Rokia Sanogo, Angelo Vanella, Alessandra Russo and Nunziatina De Tommasi 1089 N1,N2,N3-Trisisopentenyl Guanidine and N1,N2-Diisopentenyl guanidine, Two Cytotoxic Alkaloids from Alchornea cordifolia (Schumach.& Thonn.) Müll. Arg. (Euphorbiaceae) Root Barks Hélène Mavar-Manga, David Chapon, Sara Hoet, Sébastien Block, Marie-Claire. De Pauw-Gillet and Joëlle Quetin-Leclercq 1097 Indole Monoterpenes with Antichemotactic Activity from Psychotria myriantha Cláudia A. Simões-Pires, Fabianne M. Farias, Andrew Marston, Emerson F. Queiroz, Célia G. Chaves, Amélia T. Henriques and Kurt Hostettmann 1101 HPLC Based Activity Profiling for Inhibitors of Human Neutrophil Elastase in Isatis tinctoria Leaf Extracts M. Hamburger, H. G. Rüster and M. F. Melzig 1107 Variation in Artemisinin and Flavonoids Content in Different extracts of Artemisia annua L. Anna Rita Bilia, Caterina Gabriele, Maria Camilla Bergonzi, Pedro Melillo de Malgalhaes and Franco Francesco Vincieri 1111 Antifungal Evaluation of Hypericum triquetrifolium Polar Extracts Against Fusarium spp Daniele Fraternale, Alessandra Bertoli, Laura Giamperi, Anahi Bucchini, Donata Ricci, Francesco Menichini, Elena Trinciarelli and Luisa Pistelli 1117 Antioxidant Activity Analysis for the Selection of Rosmarinus officinalis L. Juan Antonio Garbarino, Nicolás Troncoso, Pia Delpiano, Loreto Carvajal and Alessandra Russo 1123 Hypericum perforatum L., H. maculatum Crantz., H. calycinum L. and H. pulchrum L.: Phytochemical and Morphological Studies Gelsomina Fico, Sara Vitalini, Noemi Colombo and Franca Tomè 1129 Chemical Composition and Antimicrobial Activities of Essential Oil of Stachys glutinosa L. from Sardinia Pintore Giorgio, Chessa Mario, Manconi Paola, Zanetti Stefania, Deriu Antonella and Tirillini Bruno 1133 Molecular Identification of Panax ginseng C.A. Meyer in Ginseng Commercial Products Paola Del Serrone, Lucilla Attorri, Bruno Gallinella, Francesca Romana Gallo, Elena Federici and Giovanna Palazzino Continued overleaf

Lipoxygenase Inhibitory Activity of Boropinic Acid, Active Principle from Boronia pinnata Massimo Curini, Francesco Epifano, Salvatore Genovese, Luigi Menghini, Donata Ricci, Daniele Fraternale, Laura Giamperi, Anahi Bucchini and Emanuele Bellacchio 1141 A Convenient Synthesis of 5′-Iodoresiniferatoxin (I-RTX) Abdellah Ech-Chahad, Lahboub Bouyazza and Giovanni Appendino 1147 Review /Account Acaricides of Natural Origin. Part 2. Review of the Literature (2002-2006) Guido Flamini 1151 Chemistry and Biological Activity of Triterpene Saponins from Medicago Species Aldo Tava and Pinarosa Avato 1159 Non-nitrogenous Plant-derived Constituents with Antiplasmodial Activity Anna Rita Bilia 1181 LIST OF AUTHORS Antonella, D ............. 1133 Appendino, G ........... 1147 Attorri, L.................. 1137 Avato, P.................... 1159 Bellacchio, E ............ 1141 Bergonzi, MC.......... 1111 Bertoli, A ................. 1117 Bilia, AR ......... 1111,1181 Block, S ................... 1097 Bouyazza, L.............. 1147 Braca, A.................... 1089 Bruno, T ................... 1133 Bucchini, A............... 1117 Bucchini, A............... 1141 Cairoli, P................... 1085 Carvajal, L................ 1123 Chapon, D................. 1097 Chaves, CG .............. 1101 Cioffi, G ................... 1089 Claire, M................... 1097 Clericuzio, M............ 1079 Colombo, N ............. 1129 Crippa, S................... 1085 Curini, M .................. 1141 de Malgalhaes, PM....1111 Delpiano, P................1123 Dos Santos, LC .........1073 Ech-Chahad, A ..........1147 Epifano, F..................1141 Farias, FM ................1101 Federici, E .................1137 Fico, G......................1129 Finzi, PV ...................1079 Flamini, G .................1151 Fraternale, D..............1117 Fraternale, D..............1141 Gabriele, C ................1111 Gallinella, B .............1137 Gallo, FR ...................1137 Garbarino, JA ............1123 Genovese, S..............1141 Giamperi, L ..............1117 Giamperi, L ...............1141 Gilardoni, G...............1079 Giorgio, P ..................1133 Hamburger, M...........1107 Henriques, AT...........1101 Hoet, S.......................1097 Hostettmann, K .........1101 Mahmood, N .............1073 Manitto, P..................1085 Marchetti, A ..............1079 Mario, C ....................1133 Marston, A ...............1101 Mavar-Manga, H.......1097 Melzig, MF................1107 Menghini, L...............1141 Menichini, F..............1117 Monti, D ....................1085 Morelli, CF................1085 Palazzino, G .............1137 Paola, M ...................1133 Pauw-Gillet, MCD ...1097 Piacente, S.................1073 Pistelli, L ...................1117 Pizza, C .....................1073 Queiroz, EF ..............1101 Quetin-Leclercq, J.....1097 Ricci, D ...........1117,1141 Russo, A...........1089,1123 Rüster, GU ................1107 Sanogo, R..................1089 Serrone, PD ...............1137 Simões-Pires, C.........1101 Simone, FD ...............1089 Speranza, G...............1085 Stefania, Z.................1133 Tava, A......................1159 Tomè, F .....................1129 Tommasi, ND............1089 Trinciarelli, E............1117 Troncoso, N...............1123 Vanella, A .................1089 Vassallo, A................1089 Vidari, G....................1079 Vincieri, FF...............1111 Vitalini, S ..................1129 Zanoni, G ..................1079

Triterpenes from Maytenus macrocarpa and Evaluation of Their Anti-HIV Activity Sonia Piacentea , Lourdes Campaner Dos Santosb , Naheed Mahmoodc and Cosimo Pizzaa,* a Dipartimento di Scienze Farmaceutiche, University of Salerno, via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy b Instituto de Quimica, UNESP, CP335, CEP 14801-970 Araraquara, SP, Brazil c Retroscreen Ltd, Academic Virology, London Hospital, Whitechapel, 64 Turner Street, London E1 2AD, U.K. pizza@unisa.it Received: September 8th, 2006; Accepted: November 2nd, 2006 Dedicated to the memory of Professor Ivano Morelli. A set of pentacyclic triterpenes has been isolated from the bark of Maytenus macrocarpa (Celastraceae). It includes two new olean-12-ene derivatives, namely 3β, 22α-dihydroxy-olean-12-en-30-oic acid (1) and 22α-hydroxy-olean-12-en-3-oxo-30-oic acid (2), and the new urs-12-ene derivative 3-(E)-coumaroyluvaol (7), along with 10 known compounds possessing olean-12- ene, urs-12-ene, lupane and friedelane skeletons. The structures have been elucidated by extensive spectroscopic methods including 1D- and 2D-NMR experiments, as well as ESI-MS analysis. All isolated compounds were tested for anti-HIV activity in C8166 cells infected with HIV-1MN. The most active compound was 22α-hydroxy-12-en-3-oxo-29-oic acid (triterpenonic acid A, 4), with an EC50 value of 1 μg/mL and a selectivity index of 35. Keywords: Maytenus macrocarpa, Celastraceae, pentacyclic triterpenes, anti-HIV activity. Species belonging to the genus Maytenus (Celastraceae) have been used as a traditional medicine in the Amazonian region against cancer, rheumatism, and inflammation [1-2]. M. macrocarpa (R & P) Briquet is endemic to the Amazonian region of Peru and an alcoholic infusion of its bark is used, generally in “aguardiente”, for the treatment of rheumatism, influenza, gastrointestinal diseases, and as an antitumor agent for skin cancer [3]. In previous papers, dammarane [3] and friedelane triterpenes [4] from the stem bark exudates, sesquiterpene polyol esters from the leaves [5], and the nortriterpenes macrocarpins A-D from the roots [6] of M. macrocarpa have been reported. Furthermore a dihydro-β-agarofuran sesquiterpene isolated from the roots of M. macrocarpa has been reported to act as a modulator of daunomycin resistance in a multidrugresistant Leishmania tropica line. [7]. Here we report the isolation and characterization of three new triterpenes from the bark of M. macrocarpa, namely 3β, 22α-dihydroxy-12-en- 30-oic acid (1), 22α-hydroxy-12-en-3-oxo-30-oic acid (2) and 3-(E)-p-coumaroyluvaol (7), along with the known olean-12-ene derivatives maytenfolic acid (3), triptotriterpenonic acid A (4), 22-epi-maytenfolic acid (5), 22-epi-triptotriterpenonic acid A (6), the urs-12-ene derivative 3-(E)-caffeoyluvaol (8), the lupane-type triterpenes 3-(E)-p-coumaroylbetulin (9), 3-(Z)-p-coumaroylbetulin (10), 3-(E)-caffeoylbetulin (11), nepeticin (12), and friedelane orthosphenic acid (13). On the basis of the anti-HIV activity reported for triterpenes closely related to compounds 1-13 isolated from M. macrocarpa [8-10], the inhibitory activity of these compounds against HIV-1 replication in acutely infected C8166 cells has been evaluated. NPC Natural Product Communications 2006 Vol. 1 No. 12 1073 - 1078

Triterpenes from Maytems macrocarpo Natural Product Communications Vol.1(12)2006 1075 allowed us to clarify the difference between the two acyl moiety identified as(E)-p-coumaroyl.In the compounds hile.in the case of 3.the ROES HMBC spectrum,the proton at 84.58 (H-3) 1(Me-30) 0 correlated with the carbon resonance at 8 167.2 H-22 28 ted I hu tha 1 s126(Me-29 3-(E)-coumaroyluvac d latio d to the The known compounds maytenfolic that 1 3B.22a-dihvdr 2-cn-30-oic carpoic acid A. maytenfolic acid (5)[16].22-epi-trip totrit acid A (6)[16].3-(E)-caf 阁 Compound 2 showed,in the ESI-MS in positive ion mode,the quasi-molecular ion [M+H]at m/471, 6ncolceular coumais)-caffeoylbetulin (11) spec secopets .11x2 with those 1.33,onc one methine to an oxygen The co-occurrence in M.macrocarpa of triterpenes aring carbor belonging to different classes is an unusual finding 30 For maytenfolic acid (3).previously isolated from M at6123.4.1435.181.0 and 2190 inc 2 aierst antileukemic xoolean-12-eno acid 13 ity has been lin esters nounds 7.8 are esters of uvaol.fo hich antiproliferative and antileukemic activity at 83.19 in the 'H NMR spectrum and 79.7 in the have been reported [20]. C NMR spectrum,observed for 1.It was confirmed Table:Anti-HIVactivity of omounds 1-13 by the long range correlations observed in the HMBC the signals at 6 1.09 Compounds proton (C-3) Thus 2 was assigned 00 a 00 22a-hydroxy-olean -0X0-30-01c acid.and named mac ula 8 und which showed the molecular ion peak [M+H 00002050m 00006500 at m/589.The 'H NMR spectrum showed seven methyl groups at 0.88(d,J=6.5 Hz),0.96(s),0.97 (d,J=6.5Hz.1.01(s.1.08(s,1.09(s,and1.17 EC =CO (s).two signals ascribable to a primary 3.08 and 3.59 (each IH,d, 1.0Hz a me ne proton linked to On the basis of the anti-HIV activity reported for the derivative bet linic acid [8-91. nd to closely related to orthosphenic acid [10],the anti 683 HIV activity of compounds 1-13 in C8166 cells HZ) 02 80 infected with HIV-IMN was tested.The most active typical of a 1.4-disub ing The NMR spectros above (Tabl h the me anism the chemical shift of C-3 and the occurrence of an

Triterpenes from Maytenus macrocarpa Natural Product Communications Vol. 1 (12) 2006 1075 allowed us to clarify the difference between the two compounds. While, in the case of 3, the ROESY spectrum showed correlations between the signal at δ 1.22 (Me-30) and the signals at δ 2.36 (H-18), 3.52 (H-22), and 1.01 (Me-28), these effects were absent in the ROESY spectrum of 1, where the signal at δ 1.26 (Me-29) showed a correlation with that at δ 1.33 (Me-27). This evidence led to the conclusion that 1 was 3β,22α-dihydroxy-olean-12-en-30-oic acid, which was named macrocarpoic acid A. Compound 2 showed, in the ESI-MS in positive ion mode, the quasi-molecular ion [M+H]+ at m/z 471, corresponding to the molecular formula C30H46O4. The compound exhibited, in its 1 H NMR spectrum, seven singlet methyl groups (δ 0.95, 1.09, 1.11 x 2, 1.13, 1.26, 1.33), one olefinic proton (δ 5.25), and one methine proton (δ 3.63) linked to an oxygen bearing carbon. In the 13C NMR spectrum the occurrence of signals for 30 carbons, including peaks at δ 123.4, 143.5, 181.0 and 219.0, suggested that 2 was an oxoolean-12-enoic acid [13]. By comparison of NMR data of 2 with those of 1 it was speculated that the position of the carbonyl group (δ 219.0) was at C-3 on the basis of the absence in 2 of the signals at δ 3.19 in the 1 H NMR spectrum and 79.7 in the 13C NMR spectrum, observed for 1. It was confirmed by the long range correlations observed in the HMBC spectrum between the proton signals at δ 1.09 (Me-23) and 1.11 (Me-24) and the carbon resonance at δ 219.0 (C-3). Thus 2 was assigned as 22α-hydroxy-olean-12-en-3-oxo-30-oic acid, and named macrocarpoic acid B. The molecular formula C39H56O4 was assigned to compound 7 on the basis of the ESI-MS spectrum, which showed the quasi-molecular ion peak [M+H]+ at m/z 589. The 1 H NMR spectrum showed seven methyl groups at δ 0.88 (d, J = 6.5 Hz), 0.96 (s), 0.97 (d, J = 6.5 Hz), 1.01 (s), 1.08 (s), 1.09 (s), and 1.17 (s), two signals ascribable to a primary alcoholic function at δ 3.08 and 3.59 (each 1H, d, J = 11.0 Hz), and a signal for a methine proton linked to an oxygen-bearing carbon at δ 4.58 (dd, J = 3.5 and 11.0 Hz). Further features were signals due to three olefinic protons at δ 5.21 (t, J = 3.5), 6.32 (d, J = 15.9 Hz ), and 7.64 (d, J = 15.9 Hz ), and signals at δ 6.83 (2H, d, J = 8.0 Hz) and 7.50 (2H, d, J = 8.0 Hz), typical of a 1,4-disubstituted aromatic ring. The 13C NMR spectroscopic data of 7 were similar to those of urs-12-en-3β,28-diol, known as uvaol [14], except for the chemical shift of C-3 and the occurrence of an acyl moiety identified as (E)-p-coumaroyl. In the HMBC spectrum, the proton at δ 4.58 (H-3) correlated with the carbon resonance at δ 167.2 (C=O), indicating that the (E)-coumaroyl group was located at C-3. Thus compound 7 was identified as 3-(E)-coumaroyluvaol, and named macrocarpol A. The known compounds maytenfolic acid (3) [11], triptotriterpenonic acid A (4) [15], 22-epimaytenfolic acid (5) [16], 22-epi-triptotriterpenonic acid A (6) [16], 3-(E)-caffeoyluvaol (8) [14], 3-(E)-pcoumaroylbetulin (9) [17], 3-(Z)-p-coumaroylbetulin (10) [18], 3-(E)-caffeoylbetulin (11) [18], nepeticin (12) [12], and orthosphenic acid (13) [12] were identified by comparison of their spectroscopic data with those reported in the literature. The co-occurrence in M. macrocarpa of triterpenes belonging to different classes is an unusual finding. For maytenfolic acid (3), previously isolated from M. diversifolia [11], antileukemic activity has been reported [11], while compounds 9-11, betulin esters, have been reported to exert antitumor promoting activity [19]. Compounds 7-8 are esters of uvaol, for which antiproliferative and antileukemic activity have been reported [20]. Table 1: Anti-HIV activity of compounds 1-13. Compounds EC50a TC50b 1 10 50 2 10 50 3 10 80 4 1 35 5 100 200 6 50 100 7 10 50 8 10 100 9 12 62 10 10 25 11 5 50 12 10 50 13 10 80 EC50a = concentration (μg/mL) that reduced by 50% the production of gp120 in infected C8166 cells. TC50b = concentration (μg/mL) that caused 50% cytotoxicity to uninfected C8166 cells. On the basis of the anti-HIV activity reported for the lupane derivative betulinic acid [8-9], and, to a minor extent, for salaspermic acid, a friedelane derivative closely related to orthosphenic acid [10], the antiHIV activity of compounds 1-13 in C8166 cells infected with HIV-1MN was tested. The most active compound was 4, with an EC50 value of 1μg/mL and a selectivity index above 30 (Table 1). The investigation of the mechanism of action of 4 revealed that it was more effective when added either