200536531 玖、發明說明： 【發明所屬之技術領域】 本發明係關於-種可抑制8型肝炎抗原之化合物及其醫藥 或食品組合物，特別為一種由棒芝菌絲體萃取出之可抑制=型 肝炎抗原之化合物及其醫藥組成物。 【先前技術】 樟芝又名牛樟益、樟疏、棒窟内藏，台灣有稱陰陽對口益。 樟芝子實體屬多年生，具有強烈沖鼻的樟樹香氣，此與—般靈 芝類有很大的差異，其外型呈板狀或鐘狀。板狀型態者，面為 橘紅(黃）色，整面全有菌孔，板底層有淺黃白色的木栓質，藉此 木栓質附著在牛樟樹中空叫内壁上生長。鐘㈣_ 層（鐘面）亦呈橘（黃）色，充滿菌孔(4〜5個菌孔/毫米），内有孢子 味極苦，新鮮時為橘紅色，之後會成為橘褐色或褐色，鐘體則 呈暗綠褐色的皮殻。以顯微鏡觀察其擔孢子，其型態為平滑益 色之透明微彎柱形。 野生的樟U生長在牛樟樹幹中空内壁上，因為這個特 性’造成很多牛樟樹倒伏。文獻記載，掉芝是在牛掉樹上目前 唯-發現的木材腐杉g，病徵為褐色腐朽，故為褐腐菌 掉芝的病原性衫強，因此牛樟樹很知此社。雖然樟芝對 牛樟樹而言是病原菌，但因樟芝價格昂貴，超過牛掉樹的經濟 價值’因此是不是牛樟樹的病原菌已經不重要了。 樟芝的培養，人I栽培技術方面，仍有待努力。所以，目 前仍是以深山採集的方式來獲得。但是採集樟芝不是件容易的 200536531 事，因為首先要尋找牛樟樹的產地。常有的困難是牛樟樹與冇 樟，兩者極為相似，不易分辨。目前最直接的方法已由藤田安 二提出，冇樟幹油是以黃樟油（safrole)與十五燒酸為主，因而有 沙士中黃樟素的味道。牛樟幹油則以松油醇（d_terpinenol)為 主，而有樟腦油的味道，藉此即可區別牛樟與冇樟。第二個困 難是要從大片樹林中找到有中空洞的樹幹才行，此相當不易。 空洞中若有樟芝，則可定期採集。 樟芝子實體（Antrodia camphorota Chang & Chou，sp· ηον·) 在台灣民俗療法，已經被使用於作為解毒劑，腹瀉，腹痛，高血壓， 皮膚癢和肝癌的治療。藻類化學的調查結果導致一系列的三萜 浠酸(triterpene acids)被分離出來。早期台灣原住民在採伐時， 無意間發現了牛樟樹上的樟芝，原住民因生活型態之故，體能 消耗量較大，肝的病變對原住民來說，是最大的威脅，民族性 使然，原住民較喜歡喝酒、宿醉在所難免，因喝酒過多導致肝 病變的比率亦是居高不下。但在喝過樟芝的烹煮液，竟可不藥 而癒、強身健體、解酒效力更是一流，至此原住民便將樟芝奉 為上品，成為原住民的傳統珍貴藥材。民間傳說對肝癌及子宮 癌特別有效，亦有用於治療急性腹痛者。 因此有鑑於： 1. 樟芝唯一寄生物種一牛樟樹，屬於保育類一級木樹種，且為 有空心的牛樟樹之不易取得； 2. 有需要對此台灣獨有的樟樹所具保肝功能予以科學性研究以 確定其臨床功效； 本案發明人乃經精深研究，發現樟芝子實體之成分中含有 200536531 本發明所述之化合物，並證明其具有抑制B型肝炎抗原之功效。 【發明内容】 本發明之目的之一在於提供一種對B型肝炎抗原具有抑制 效果的化合物。 本發明之目的之二在於提供一種對B型肝炎抗原具有抑制 效果的醫藥或食品組合物。 可達成上述目的之一種可抑制B型肝炎表面或e抗原之化 合物，其具有以下結構式： 〇200536531 发明 Description of the invention: [Technical field to which the invention belongs] The present invention relates to a compound capable of inhibiting hepatitis 8 antigen and a pharmaceutical or food composition thereof, particularly a kind of inhibitory substance extracted from mycelium of C. lucidum = Hepatitis antigen compounds and pharmaceutical compositions thereof. [Previous technology] Antrodia cinnamomea is also known as Niu Zhangyi, Zhangshu, and stick caves. Taiwan is known as Yin-Yang counterpart. Antrodia camphorata fruit body is perennial and has a strong nose-flavoring camphor tree aroma. This is very different from ordinary ganoderma lucidum, and its appearance is plate-shaped or bell-shaped. Those with a plate-like shape have an orange-red (yellow) color, and the entire surface is full of pores. The bottom of the plate is light yellow and white woody cortex, which is attached to the hollow wall of the camphor tree. The layer of bell ㈣ (bell face) is also orange (yellow), full of pores (4 ~ 5 pores / mm), and has a bitter spore flavor. It is orange-red when fresh, and then becomes orange or brown. The bell body has a dark green brown leather case. Observing its basidiospores with a microscope, its shape is a smooth and curved transparent micro-curved column. Wild Cinnamomum camphora grows on the hollow inner wall of the camphor tree trunk, because this feature ’causes many camphor trees to fall. It is documented that the loss of Zhizhi is the only wood rot cedar g found on cattle and trees. The disease is brown and rotten. Therefore, the pathogen of brown rot fungi is strong. Therefore, A. camphora knows this company very well. Although Antrodia camphorata is a pathogenic fungus to Antrodia camphorata, it is not important whether it is a pathogenic fungus of Antrodia camphorata because it is expensive and exceeds the economic value of the cow. The cultivation of Antrodia cinnamomea and human I cultivation techniques still need to be worked on. Therefore, it is still obtained by deep mountain collection. But collecting Antrodia camphorata is not an easy 200536531 thing, because first of all, it is necessary to find the source of Antrodia camphorata. Common difficulties are N. camphor tree and camphor tree, which are very similar and difficult to distinguish. At present, the most direct method has been proposed by Fujita Anji. The dried camphor oil is mainly safrole and fifteen burning acids, so it has the flavor of safrole in SARS. Dried camphor oil is mainly composed of terpinenol and has the taste of camphor oil, which can distinguish camphor and camphor. The second difficulty is to find a hollow trunk from a large forest, which is not easy. If there is Antrodia in the cavity, it can be collected regularly. Antrodia camphorota Chang & Chou, sp. Ηον · is a folk remedy in Taiwan that has been used as an antidote for diarrhea, abdominal pain, hypertension, itchy skin and liver cancer. Investigation of algae chemistry led to the isolation of a series of triterpene acids. In the early days, the indigenous people of Taiwan discovered the Antrodia camphorata tree inadvertently during harvesting. Due to their lifestyles, the indigenous people consumed a large amount of energy. The liver disease was the greatest threat to the indigenous people. Nationality As a result, Aboriginal people prefer to drink and hangovers are inevitable. The rate of liver disease caused by excessive drinking is also high. However, after drinking the cooking solution of Antrodia camphorata, it can be cured without medicine, strengthen the body, and the hangover effect is first-class. At this time, the Aboriginal people have regarded Antrodia camphorata as a top grade, and became the traditional precious medicinal materials of the Aboriginal people. Folklore is particularly effective for liver cancer and uterine cancer, and it is also used to treat acute abdominal pain. Therefore, it is considered that: 1. Antrodia camphora, the only parasitic species of Antrodia camphorata, is a first-class wood species of conservation type, and it is difficult to obtain the hollow Antrodia camphora; 2. It is necessary to scientifically study the liver protection function of the camphor tree unique to Taiwan. Sexual research to determine its clinical efficacy. The inventor of this case conducted intensive research and found that the components of Antrodia camphorata fruit body contained 200536531 the compound described in the present invention, and proved that it has the effect of inhibiting hepatitis B antigen. SUMMARY OF THE INVENTION An object of the present invention is to provide a compound having an inhibitory effect on a hepatitis B antigen. Another object of the present invention is to provide a pharmaceutical or food composition having an inhibitory effect on hepatitis B antigen. A compound capable of inhibiting the surface of Hepatitis B or e-antigen, which can achieve the above object, has the following structural formula: 〇
【實施方式】 (一） 有機體的來源 本實施例所使用之菌株i CCRC-35396是購買 自食品工業研究發展學會。 (二） 有機體的發酵 將CCRC-35396菌株接種到1L的媒介（1.0%葡萄糖， 0.5%黃豆粉狀物，0.5%消化蛋白質，0.01%MgS04，0.01%去 沫劑（KM-72 antifoam)，ρΗ4·0)於 2-L Hinton 燒瓶中，在 28° C 下旋轉振蘯十天。培養出之菌絲體於無菌室中轉移到一内含 120L上述媒介的200-L醱酵器，在28°C下發酵十二天。 200536531 (三） 化合物的萃取和分離· 發酵後所得物質在真空下濃縮成一殘留物。該殘留物（1公 斤）以丙酮萃取，其丙酮萃取物利用矽膠管柱進行層析，並由正 己烷至乙酸乙酯（EtOAc)作梯度沖提以獲得四種區分物。其第二 區分物（沖提液：正己烷/乙酸乙酯=5/1)在一矽膠管柱上再層析 (rechromatographed)，用正己烷/乙酸乙酯（1〇:1)沖提得到十區 分物。其中第三和第四區分物結合且在一管柱（Sephadex LH-20) 上利用甲醇（MeOH)進行層析以獲得本發明之化合物（15 mg)。 (四） 化合物性質及結構鑑定 該化合物之熔點係利用一微熔點儀器（Yanaco MP-I3)和一 未校正的溫度計來決定。 紅外線光譜是以 Nicolet Avatar 320 FT-IR spectrometer 記錄 之。 4 和 13C NMR 圖譜是利用 Varian Unity INOVA 500 spectrometer 湏丨J 得。 UV 光譜是利用 Hitachi U-3200 spectrometer 量測。 質譜是由 Finnigan GCQ spectrometer 獲得。 其紅外線光譜顯示之吸光值為N-H或O-H基在3230 cnT1 和C=0基在1764和1705 cm·1。此1H NMR光譜（表一）顯示二 個序列（doublets) ·· SH7.49(2H，d，J=8.5Hz)和 6.97(2H，d，J=8.5Hz) 200536531 屬於苯環的範圍，該化合物具有一 1，4-二取代苯環。信號在 δΗ5·48(1Η，ΐ，J=6.5Hz)，4.57(2H，d，J=6.5Hz)，1.79(3H，s)和 1.74(3H，s)時，暗示氧化的異戊烯不明確部分（oxygenated prenyl moiety)的存在。此外，經由 δΗ2·49(2Η，(Μ=7.5Ηζ)、2.03(lH，m) 和0.88 (6H，d，J=7.0Hz)的信號指出異丁基的存在。13C NMR和 DEPT光譜則顯示三個甲基、二個碳烯（methylene)、四個 methine信號及七個四級碳。在這些四級碳中，δ(： 171.80和 171.15的信號指出具有二個00基，δ〇：139·14和138.73(或 138.71)的信號是歸因於一雙鍵。HMBC光譜，H-12顯示之交 叉峰係為C-2、C-3、C-4及H-7、H-ll、C-4之相互關係。它指 出異丁基和芳香環皆與此雙鍵形成鍵結，該雙鍵係與至少一 00基結合。再者，在H-1’和C_9之間觀察到的交叉峰，顯示 prenyloxy是隸屬於該芳香環。因此，該化合物的結構係可推斷 為C=0基在SC 171.15共振。為決定該化合物的完全結構，執 行一單晶體X-射線散射分析（表二）。它指出一琥珀醯亞胺 (succinimide)之不確定部分的存在，其具有一異丁基和一芳香環 附於其上。 如圖一所示，該化合物的結構可碟定為3-isobutyl-4-{4-[(3-甲基-2-butenyl)oxy]phenyl}-2,5-dihydro-lH-2,5-pyrroledione，其 為一新穎的 pyrroledione，名為 antropyrroledione。其為一黃色 晶體，熔點為 90-91°C;UV(MeOH):Xmaxnm(logs)為 202 (4.57)、 200536531 230 (4·34)、355 (3·70) ; IR (KBr)為 3230、2928、2872、1764、 1705、1601、1509、1354、1248、1173、982 cm-1; 4 和 13C NMR， 在表一中，CIMS係使用氨作為試藥氣體，測得m/z 331 (M+CH4)+、263 、145 ，顯示[M+NH4]離子為 m/z (Cl9H23N〇3+NH4)。 (五）抗B型肝炎病毒分析 HBV的細胞株MS-G2是鋪設在一密度為3x 105 cells/ml-well的24格平底組織培養盤。隔夜後，每個細胞適當 地附著於其上；這細胞是經由檢測樣品測試過。將二甲亞石風 (DMSO)加到每個培養基作為溶媒控制，檢測樣品是分別溶解在 濃度為5、25和50 mM的DMSO中。媒介中DMSO的濃度係 維持在不大於2.5 ml/m卜以保證那個它不影響MS-G2細胞的成 長。其次’每個抗病毒試驗組在第3天收集培養基。抗病毒活 性的決定係經由HBsAg和HBeAg的改變，利用酵素-連結免 疫吸附試驗（ELISA)在檢測試劑存在或不存在的情況下進行分 析’結果於波長492nm ，使用一分光比色計DYNATECH MR7000型ELISA reader獲得，和DMSO溶媒控制組比較可計 算其抑制百分率（％)，抑制百分率（叫^一樣品的吸光值 (492nm) /DMSO 的吸光值（492nm)] xl 00。 该化合物的抗病毒活性是藉由MS-G2細胞抗b型肝炎病毒 之體外试驗來评估。該化合物在1 〇〇mM及5〇ηιΜ之無細胞毒性 200536531 抑制率分別為 濃度中’能有效地拍^岳丨口 仰制HBsAg和HBeAg表現 76.5 和 58.2% ; 35 4 ”·2 和 12.8% 〇 本發明所提出之可抑制B型肝炎抗原之化合物及其醫藥或 食品組合物’與其他習用物質或產品相互比較時，更具備提高 了 B型肝炎抗原的抑制率的優點。 ㊁ 上列评細說明乃針對本發明之-可行實施例進行具體說 明，惟該實施例並非用以限制本創作之專利範圍，凡未脫離本 創作技藝精神所為之等效實施或變更，均應包含於本案之專利 範圍中。 综上所述’本案不僅於技術思想上確屬創新，並具備習用 方法所不及之上述多項功效，已充分符合新穎性及進步性之法 定創作專料件，爰依法提μ請，料t局核准本件發明專 利申請案，以勵創作，至感德便。 【圖式簡單說明】 圖一為本發明之化合物結構圖。 200536531 表一、該化合物之13(：(1261^)及111(5001^)^111圖譜資料（於€〇<：1/) 位置 δ〇 DEPT 6h [mult., ^(Hz)] HMBC 2 171.80 C 3 139.14 c H-12，H-13 4 138.73^ c H-7，H-11，H_12 5 171.15 c 6 121.13 c H-8，H-10，H-12 7 130.92 CH 7.49 (d, 8.5) 8 114.82 CH 6.97(48.5) H-7，H-11 9 160.02 C Η-7，Η-8,Η-10，Η-11,Η-Γ 10114.82 CH 6.97(48.5) H-7，H-11 11130.92 CH 7.49 (d, 8.5) 1232.78 ch2 2.49(d,7.5) H-13，H-14，H-15 1328.07 CH 2.03 (m) H-12，H_14，H-15 1422.70 ch3 0.88 (d, 7.0) H-12，H-13 1522.70 ch3 0.88(47.0) H-12，H-13 Γ 64.86 ch2 4.57 (d, 6.5) 2, 119.19 CH 5.48 (t, 6.5) Η-Γ，Η4’,Η-5’ 3, 138·71办 C H-l’,H4’，H-5’ 4, 25.81 ch3 1.79 (s) H-2，，H-5， 5, 18.20 ch3 1.74 (s) H-2，，H4， a 係用於 DEPT，COSY，HMQC，及 HMBC 試驗. b係用於内部變化[Embodiments] (1) Source of organisms The strain i CCRC-35396 used in this example was purchased from the Food Industry Research and Development Institute. (II) Fermentation of organisms: CCRC-35396 strain was inoculated into 1 L of medium (1.0% glucose, 0.5% soybean powder, 0.5% digested protein, 0.01% MgS04, 0.01% defoamer (KM-72 antifoam), ρΗ4 0) In a 2-L Hinton flask, shake and shake at 28 ° C for ten days. The cultured mycelium was transferred to a 200-L fermenter containing 120L of the above-mentioned medium in a sterile room, and fermented at 28 ° C for 12 days. 200536531 (3) Extraction and separation of compounds · The material obtained after fermentation is concentrated under vacuum to a residue. The residue (1 kg) was extracted with acetone, and the acetone extract was chromatographed on a silica gel column and subjected to gradient elution from n-hexane to ethyl acetate (EtOAc) to obtain four kinds of fractions. The second fraction (eluent: n-hexane / ethyl acetate = 5/1) was rechromatographed on a silica gel column, and the solution was extracted with n-hexane / ethyl acetate (10: 1) to obtain Ten divisions. Wherein the third and fourth distinguishers were combined and chromatographed on a column (Sephadex LH-20) using methanol (MeOH) to obtain the compound of the present invention (15 mg). (IV) Identification of compound properties and structure The melting point of the compound was determined using a micro-melting point instrument (Yanaco MP-I3) and an uncalibrated thermometer. The infrared spectrum was recorded with a Nicolet Avatar 320 FT-IR spectrometer. 4 and 13C NMR spectra were obtained using Varian Unity INOVA 500 spectrometer meter 丨 J. The UV spectrum is measured using the Hitachi U-3200 spectrometer. Mass spectra were obtained from the Finnigan GCQ spectrometer. The infrared spectrum shows the absorption values of N-H or O-H groups at 3230 cnT1 and C = 0 groups at 1764 and 1705 cm · 1. This 1H NMR spectrum (Table 1) shows two sequences (doublets) · SH7.49 (2H, d, J = 8.5Hz) and 6.97 (2H, d, J = 8.5Hz) 200536531 belongs to the range of benzene rings, which The compound has a 1,4-disubstituted benzene ring. Signals at δΗ5 · 48 (1Η, ΐ, J = 6.5Hz), 4.57 (2H, d, J = 6.5Hz), 1.79 (3H, s), and 1.74 (3H, s), suggest that the oxidized isoprene does not The presence of an oxygenated prenyl moiety. In addition, the presence of isobutyl is indicated by signals of δΗ2.49 (2Η, (M = 7.5Ηζ), 2.03 (lH, m), and 0.88 (6H, d, J = 7.0Hz). 13C NMR and DEPT spectra show Three methyl, two ethylene, four methine signals, and seven quaternary carbons. Among these quaternary carbons, the signals of δ (: 171.80 and 171.15 indicate two 00 groups, δ0: 139 · The signals of 14 and 138.73 (or 138.71) are attributed to a double bond. HMBC spectrum, the cross-peaks shown by H-12 are C-2, C-3, C-4 and H-7, H-ll, The relationship between C-4. It indicates that both isobutyl and aromatic rings form a bond with this double bond, which is bonded to at least one 00 group. Furthermore, the observed between H-1 'and C_9 Crossed peaks, showing that prenyloxy belongs to the aromatic ring. Therefore, the structure of the compound can be inferred that the C = 0 group resonates at SC 171.15. To determine the complete structure of the compound, a single crystal X-ray scattering analysis is performed (Table 2 It indicates the existence of an indeterminate part of succinimide with an isobutyl group and an aromatic ring attached to it. As shown in Figure 1, the compound The structure can be determined as 3-isobutyl-4- {4-[(3-methyl-2-butenyl) oxy] phenyl} -2,5-dihydro-lH-2,5-pyrroledione, which is a novel pyrroledione , Named antropyrroledione. It is a yellow crystal with a melting point of 90-91 ° C; UV (MeOH): Xmaxnm (logs) is 202 (4.57), 200536531 230 (4 · 34), 355 (3 · 70); IR (KBr) is 3230, 2928, 2872, 1764, 1705, 1601, 1509, 1354, 1248, 1173, 982 cm-1; 4 and 13C NMR. In Table 1, the CIMS system uses ammonia as the reagent gas. m / z 331 (M + CH4) +, 263, 145, showing that [M + NH4] ion is m / z (Cl9H23N03 + NH4). (5) Hepatitis B virus-resistant HBV cell line MS-G2 It was laid on a 24-cell flat-bottomed tissue culture plate with a density of 3x 105 cells / ml-well. After overnight, each cell was properly attached to it; the cells were tested via a test sample. Dimethylite ( DMSO) was added to each medium as a vehicle control. The test samples were dissolved in DMSO at concentrations of 5, 25, and 50 mM. The concentration of DMSO in the medium was maintained at no more than 2.5 ml / m to ensure that it did not affect Growth of MS-G2 cells. Next ', the culture medium was collected on the third day for each antiviral test group. The determination of antiviral activity is based on the change of HBsAg and HBeAg, and the enzyme-linked immunosorbent assay (ELISA) is used to analyze in the presence or absence of detection reagents. The result is at a wavelength of 492nm and a spectrophotometer DYNATECH MR7000 is used. Obtained by ELISA reader, and compared with the DMSO vehicle control group, the percentage inhibition (%), the percentage inhibition (called the absorbance of a sample (492nm) / the absorbance of DMSO (492nm)] x 100 are calculated. The antiviral activity of the compound It was evaluated by an in vitro test of MS-G2 cells against hepatitis B virus. The compound has no cytotoxicity at 100 mM and 50 μM. 200536531 Inhibition rates are in concentrations, respectively, and can effectively shoot The performance of HBsAg and HBeAg is 76.5 and 58.2%; 35 4 ”· 2 and 12.8% 〇 When the compound and the medicine or food composition of the present invention which can inhibit hepatitis B antigen are compared with other conventional substances or products, It also has the advantage of increasing the inhibition rate of hepatitis B antigen. 细 The detailed description of the above review is specifically for the feasible embodiment of the present invention, but this embodiment is not It is not intended to limit the scope of the patent for this creation, and any equivalent implementation or change that does not depart from the spirit of this creative technique should be included in the scope of the patent for this case. In summary, 'This case is not only innovative in terms of technical ideas, And has many of the above-mentioned effects that are not used by conventional methods, and has been fully in line with the novelty and progress of the statutory creative special materials. According to the law, we request that the Bureau of Approval of this invention patent application to encourage creativity, [Brief description of the figure] Figure 1 shows the structure of the compound of the invention. 200536531 Table 1. 13 (:( 1261 ^) and 111 (5001 ^) ^ 111 of the compound ) Position δ〇DEPT 6h [mult., ^ (Hz)] HMBC 2 171.80 C 3 139.14 c H-12, H-13 4 138.73 ^ c H-7, H-11, H_12 5 171.15 c 6 121.13 c H- 8, H-10, H-12 7 130.92 CH 7.49 (d, 8.5) 8 114.82 CH 6.97 (48.5) H-7, H-11 9 160.02 C Η-7, Η-8, Η-10, Η-11 , Η-Γ 10114.82 CH 6.97 (48.5) H-7, H-11 11130.92 CH 7.49 (d, 8.5) 1232.78 ch2 2.49 (d, 7.5) H-13, H-14, H-15 1328.07 CH 2.03 (m) H-12, H_14 H-15 1422.70 ch3 0.88 (d, 7.0) H-12, H-13 1522.70 ch3 0.88 (47.0) H-12, H-13 Γ 64.86 ch2 4.57 (d, 6.5) 2, 119.19 CH 5.48 (t, 6.5) Η-Γ, Η4 ', Η-5' 3, 138 · 71 Office C H-1 ', H4', H-5 '4, 25.81 ch3 1.79 (s) H-2, H-5, 5, 18.20 ch3 1.74 (s) H-2 ,, H4, a are used for DEPT, COSY, HMQC, and HMBC tests. b is used for internal changes
12 200536531 表二、該化合物之層析數據 化學式 分子量 space group 4) ΜΑ) c(A) α〇 β(°) γ(°) F(A3)12 200536531 Table 2. Chromatographic data of this compound Chemical formula Molecular weight space group 4) ΜΑ) c (A) α〇 β (°) γ (°) F (A3)
Aaic(Mg/m3) Ζ μ(ΜοΚα)(ιηιη4) F(000) λ(Α) 溫度（Κ) 晶體大小（mm) θ範圍（°) reflections collected i ndependent reflections 精製法Aaic (Mg / m3) Z μ (ΜοΚα) (ιηιη4) F (000) λ (Α) Temperature (K) Crystal size (mm) θ range (°) reflections collected i ndependent reflections
goodness-of-fit on F2 Rgoodness-of-fit on F2 R
Rw largest diff· peak and hole (e人”) c19h23no3 313.38 tridmic PI 6.4185(3) 12.4449(5) 12.5861(5) 111.873(1) 103.993(1) 96.333(1) 882.59(6) 1.179 2 0.079 336 0.71073 295 0.40x0.20x0.20 1.97-27.50 9132 4059 full-matrix least squares on F2 1.004 0.0490 0.0918 0.414 and-0.244Rw largest diff · peak and hole (e person)) c19h23no3 313.38 tridmic PI 6.4185 (3) 12.4449 (5) 12.5861 (5) 111.873 (1) 103.993 (1) 96.333 (1) 882.59 (6) 1.179 2 0.079 336 0.71073 295 0.40x0.20x0.20 1.97-27.50 9132 4059 full-matrix least squares on F2 1.004 0.0490 0.0918 0.414 and-0.244
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