WO2022142159A1 - 一种Icetexane型松香烷二萜的制备方法 - Google Patents

一种Icetexane型松香烷二萜的制备方法 Download PDF

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WO2022142159A1
WO2022142159A1 PCT/CN2021/099948 CN2021099948W WO2022142159A1 WO 2022142159 A1 WO2022142159 A1 WO 2022142159A1 CN 2021099948 W CN2021099948 W CN 2021099948W WO 2022142159 A1 WO2022142159 A1 WO 2022142159A1
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icetexane
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rosinane
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diterpene
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邓旭
周应军
曹伟
刘婷婷
杨舒婷
曾光尧
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Central South University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/001—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain
    • C07C37/002—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain by transformation of a functional group, e.g. oxo, carboxyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
    • C07C2603/26—Phenanthrenes; Hydrogenated phenanthrenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/30—Ortho- or ortho- and peri-condensed systems containing three rings containing seven-membered rings
    • C07C2603/32—Dibenzocycloheptenes; Hydrogenated dibenzocycloheptenes

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  • the invention relates to the technical field of drug synthesis, in particular to a preparation method of Icetexane-type rosinane diterpenes.
  • Icetexane-type rosinane diterpenes are a kind of B-ring-expanded rosinane diterpenoids. There are about 70 kinds of natural products of this type that have been reported, which are widely distributed and found in plants of many families.
  • (-)-Barbatusol was first isolated from Coleus barbatus Bentham, an Icetexane-type rosinane diterpene. Animal experiments show that it has a strong antihypertensive activity.
  • (-)-Barbatusol (CAS 88515-76-8) is also present in Salvia gravwalskii.
  • (-)-Barbatusol in plants is relatively low, and it is mainly prepared by synthetic methods.
  • the total synthesis of Icetexane-type rosinane diterpenes is based on a metal-mediated cycloisomerization strategy.
  • the technical problem to be solved by the present invention is: a preparation method of Icetexane-type rosinane diterpene, and the preparation method has good selectivity.
  • the technical solution provided by the present invention is: a preparation method of Icetexane-type rosinane diterpene, comprising the following steps:
  • the rearrangement system includes a rearrangement reagent and a rearrangement reaction solvent
  • the rearrangement reagents include organophosphine and azo reagents.
  • the preparation method further includes the process of separating and purifying the raw material carnosic acid (Carnosic Acid (1)) from the rosemary extract; wherein, the structural formula of the carnosic acid is as follows:
  • the process of separation and purification includes the following operations:
  • Carnosic acid was prepared from rosemary extract by dissolving, filtering and recrystallization.
  • the rosemary extract is a rosemary extract with a mass fraction of about 60% carnosic acid.
  • the solvent in the dissolving process is at least one of petroleum ether, ethyl acetate, tetrahydrofuran, diethyl ether, 1,2-dichloroethane, toluene, chlorobenzene, cyclohexane and n-heptane .
  • the solvent petroleum ether and ethyl acetate mixed solvent in the dissolving process are provided.
  • the volume ratio of the petroleum ether and ethyl acetate is about 1:3.
  • the recrystallization solvent is at least one of diethyl ether, tetrahydrofuran, acetone, methanol, ethanol, isopropanol, n-butanol and ethyl acetate.
  • the recrystallization solvent is ethanol.
  • the methylation system includes a methylation reagent, a base and a methylation reaction solvent.
  • the methylating agent is at least one of methyl iodide, diethyl sulfate, diazomethane and trimethylsilyldiazomethane.
  • the methylating reagent is diazomethane.
  • the base is at least one of carbonate, triethylamine and 4-dimethylaminopyridine.
  • the carbonate is at least one of potassium carbonate and cesium carbonate.
  • the methylation reaction solvent is at least one of acetone, dimethyl sulfoxide, dimethylformamide, methanol, tetrahydrofuran, toluene and chlorobenzene.
  • the methylation reaction solvent is methanol.
  • the reduction system includes a reduction reagent and a reduction reaction solvent.
  • the reducing agent is lithium aluminum hydride, sodium borohydride, diisobutylaluminum hydride, and sodium dihydrobis(2-methoxyethoxy)aluminate.
  • the reducing agent is lithium aluminum hydride.
  • the reduction reaction solvent is at least one of tetrahydrofuran, methyltetrahydrofuran, diethyl ether, methyl tert-butyl ether and toluene.
  • the reduction reaction solvent is tetrahydrofuran.
  • the azo reagent is at least one of diisopropyl azodicarboxylate (DIAD) and diethyl azodicarboxylate (DEAD).
  • DIAD diisopropyl azodicarboxylate
  • DEAD diethyl azodicarboxylate
  • the organic phosphine includes at least one of triphenylphosphine (PPh 3 ), tri-tert-butylphosphine, tricyclohexylphosphine, and binaphthyldiphenylphosphine (BINAP).
  • Ph 3 triphenylphosphine
  • BINAP binaphthyldiphenylphosphine
  • the substance ratio of the organic phosphine and the azo reagent is 0.5:1 to 5:1.
  • the concentration of the intermediate 3 in the rearrangement system ranges from 0.01 mol/L to 5.0 mol/L.
  • the rearrangement reagents are PPh 3 and DIAD.
  • the rearrangement reaction solvent is at least one of tetrahydrofuran, methyltetrahydrofuran, 1,4-dioxane, diethyl ether, methyl tert-butyl ether and toluene.
  • the rearrangement reaction solvent is tetrahydrofuran.
  • the preparation method of Icetexane-type rosinane diterpene according to the embodiment of the present invention has at least the following beneficial effects: using organic phosphine and azo reagent, the reduced carnosic acid derivative is prepared into Icetexane-type rosinane with high efficiency and high selectivity
  • the diterpene; the preparation method of the present invention has the characteristics of short reaction time, high selectivity, high yield, large-scale preparation, and no need for protection in key steps, and can be widely popularized and applied.
  • Fig. 1 is the synthetic route diagram of the embodiment of the present invention.
  • reaction yield of each step is calculated as the separation yield of column chromatography, and the reaction of each step is detected by Qingdao silica gel thin layer analysis plate under UV, and the ethanol solution of sulfuric acid and phosphomolybdic acid is soaked and heated for color development.
  • NMR spectra were obtained by Bruker Advance 500 (1H: 500MHz, 13C: 125MHz). The following abbreviations are used for the split situation at that time, s for singlet, d for doublet, t for triplet, q for quartet, m for multiplet, and b for broad.
  • the embodiment of the present invention is: a kind of preparation method of Icetexane type rosinane diterpene, as shown in Figure 1, comprises the following steps:
  • the amount of ethyl acetate each time was 30 mL. It was dried with anhydrous sodium sulfate, and subjected to silica gel column chromatography (volume ratio of PE (petroleum ether) to EA (ethyl acrylate) was 10:1) to obtain 945 mg of the intermediate (yellow solid, yield 91%).
  • Embodiments of the present invention also include the purification of rhamnosolic acid, including the following operations:
  • the rosemary extract (60%, 20 g) was dissolved in ethyl acetate (500 mL), and petroleum ether (150 mL) was slowly added thereto under stirring. After stirring at room temperature for half an hour, the insoluble solution was filtered off. The filtrate was collected and partially concentrated, and then recrystallized with ethanol to obtain high-purity carnosic acid (95%, 9 g).
  • the preparation method of Icetexane-type rosinane diterpenes utilizes triphenylphosphine and azo reagent to prepare Icetexane-type rosinane diterpenes with high efficiency and high selectivity from reduced carnosic acid derivatives.
  • the preparation method of the present invention has the characteristics of high selectivity, high yield, large-scale preparation, and no need for protection in key steps, and can be widely popularized and applied.

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  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Steroid Compounds (AREA)

Abstract

本发明公开了一种Icetexane型松香烷二萜的制备方法，包括以下步骤：S1：将鼠尾草酸添加至甲基化体系中，固液分离，收集固相得到中间体2；S2：将所述中间体2添加至还原体系中，固液分离，收集固相得到制备中间体3；S3、将所述中间体3添加至重排体系中，固液分离，收集固相得到制备所述Icetexane型松香烷二萜；本发明的合成方法具有反应时间短，选择性高，产率高，可规模化制备、关键步骤无需保护的特点，可广泛推广应用。

Description

一种Icetexane型松香烷二萜的制备方法 技术领域
本发明涉及药物合成技术领域，具体涉及一种Icetexane型松香烷二萜的制备方法。
背景技术
Icetexane型松香烷二萜是一种B环扩环型松香烷二萜类成分，目前已经报道的该类天然产物约有70余种，分布较为广泛，在多个科的植物中均有发现。(-)-Barbatusol最早从髯毛鞘蕊花(Coleus barbatus Bentham)中分离得到一种Icetexane型松香烷二萜，动物实验表明其具有较强的降血压活性。(-)-Barbatusol(CAS 88515-76-8)也存在于甘西鼠尾草(Salvia przewalskii)中。
(-)-Barbatusol在植物体中含量较低，主要通过合成方法制备。Icetexane型松香烷二萜的全合成基于金属介导的环异构化反应策略。相关技术中，利用路易斯酸催化的分子内傅克反应(Friedel-Crafts)环化全合成barbatusol消旋体；此外，也有基于丰产天然产物的半合成策略报道；以迷迭香中的丰产天然产物鼠尾草酸为原料，通过强酸催化的碳正离子重排反应得到Icetexane型二萜衍生物的混合物，再通过官能团转换得到其他Icetexane型松香烷二萜；以(+)-Pisiferic acid(花柏酸)为原料合成(-)-pisiferin(CAS 110659-76-2)、(-)-barbatusol等Icetexane型松香烷二萜，其关键步骤为利用还原的(+)-Pisiferic acid衍生物在质子酸条件下，发生碳正离子重排获得扩环型产物。然而上述方法化学选择性差，得到的是混合物。
因此，需要一种Icetexane型松香烷二萜的制备方法，该方法选择性好。
发明内容
本发明要解决的技术问题为：一种Icetexane型松香烷二萜的制备方法，该制备方法选择性好。
为解决上述技术问题，本发明提供的技术方案为：一种Icetexane型松香烷二萜的制备方法，包括如下步骤：
S1、甲基化：将鼠尾草酸(Carnosic Acid)添加至甲基化体系中，固液分离，收集固相得到中间体2；
Figure PCTCN2021099948-appb-000001
S2、还原：将所述中间体2添加至还原体系中，固液分离，收集固相得到中间体3；
Figure PCTCN2021099948-appb-000002
S3、重排：将所述中间体3添加至重排体系中，固液分离，收集固相得到所述Icetexane型松香烷二萜；
Figure PCTCN2021099948-appb-000003
其中，所述重排体系包括重排试剂和重排反应溶剂；
所述重排试剂包括有机膦和偶氮试剂。
根据本发明的一些实施方式，所述制备方法还包括将原料鼠尾草酸(Carnosic Acid(1))是从迷迭香提取物中分离纯化的过程；其中，所述鼠尾草酸的结构式如下：
Figure PCTCN2021099948-appb-000004
根据本发明的一些实施方式，所述分离纯化的过程包括以下操作：
以迷迭香提取物为原料，通过溶解、过滤和重结晶制备鼠尾草酸。
根据本发明的一些实施方式，所述迷迭香提取物为质量分数约为60％的鼠尾草酸的迷迭香提取物。
根据本发明的一些实施方式，所述溶解过程中的溶剂为石油醚、乙酸乙酯、四氢呋喃、乙醚、1，2-二氯乙烷、甲苯、氯苯、环己烷和正庚烷至少一种。
根据本发明的一些实施方式，所述溶解过程中的溶剂石油醚和乙酸乙酯混合溶剂。
根据本发明的一些优选实施方式，所述石油醚和乙酸乙酯的体积之比约为1：3。
根据本发明的一些实施方式，所述重结晶溶剂为乙醚、四氢呋喃、丙酮、甲醇、乙醇、异丙醇、正丁醇和乙酸乙酯中的至少一种。
根据本发明的一些优选实施方式，所述重结晶溶剂为乙醇。
根据本发明的一些实施方式，所述甲基化体系包括甲基化试剂、碱和甲基化反应溶剂。
根据本发明的一些实施方式，所述甲基化试剂为碘甲烷、硫酸二乙酯、重氮甲烷和三甲硅基重氮甲烷中的至少一种。
根据本发明的一些优选实施方式，所述甲基化试剂为重氮甲烷。
根据本发明的一些实施方式，所述碱为碳酸盐、三乙胺和4-二甲氨基吡啶中的至少一种。
根据本发明的一些实施方式，所述碳酸盐为碳酸钾和碳酸铯中的至少一种。
根据本发明的一些实施方式，所述甲基化反应溶剂为丙酮、二甲基亚砜、二甲基甲酰胺、甲醇、四氢呋喃、甲苯和氯苯中的至少一种。
根据本发明的一些优选实施方式，所述甲基化反应溶剂为甲醇。
根据本发明的一些实施方式，所述还原体系包括还原试剂和还原反应溶剂。
根据本发明的一些实施方式，所述还原试剂为氢化锂铝、硼氢化钠、二异丁基氢化铝和二氢双(2-甲氧乙氧基)铝酸钠。
根据本发明的一些实施方式，所述还原试剂为氢化锂铝。
根据本发明的一些实施方式，所述还原反应溶剂为四氢呋喃、甲基四氢呋喃、乙醚、 甲基叔丁基醚和甲苯中的至少一种。
根据本发明的一些优选实施方式，所述还原反应溶剂为四氢呋喃。
根据本发明的一些实施方式，所述偶氮试剂为偶氮二甲酸二异丙酯(DIAD)和偶氮二甲酸二乙酯(DEAD)中的至少一种。
根据本发明的一些实施方式，所述有机膦包括三苯基膦(PPh 3)、三叔丁基膦、三环己基膦和联萘二苯基膦(BINAP)中的至少一种。
根据本发明的一些实施方式，所述有机膦和偶氮试剂的物质的量之比为0.5：1～5：1。
根据本发明的一些实施方式，所述中间体3在重排体系中的浓度范围为0.01mol/L～5.0mol/L。
根据本发明的一些实施方式，所述重排试剂为PPh 3和DIAD。
根据本发明的一些实施方式，所述重排反应溶剂为四氢呋喃、甲基四氢呋喃、1，4-二氧六环、乙醚、甲基叔丁基醚和甲苯中的至少一种。
根据本发明的一些实施方式，所述重排反应溶剂为四氢呋喃。
根据本发明实施方式的Icetexane型松香烷二萜的制备方法，至少具备如下有益效果：利用有机膦和偶氮试剂，将还原的鼠尾草酸衍生物高效、高选择性的制备成Icetexane型松香烷二萜；本发明制备方法具有反应时间短，选择性高，产率高，可规模化制备、关键步骤无需保护的特点，可广泛推广应用。
附图说明
图1为本发明实施例的合成路线图。
具体实施方式
以下将结合实施例对本发明的构思及产生的技术效果进行清楚、完整地描述，以充分地理解本发明的目的、特征和效果。显然，所描述的实施例只是本发明的一部分实施例，而不是全部实施例，基于本发明的实施例，本领域的技术人员在不付出创造性劳动的前提下所获得的其他实施例，均属于本发明保护的范围。
以下各步反应所用的化学试剂都是商业可得的原料，无须进一步处理。各步反应产 率计算为柱层析分离收率，各步反应由青岛硅胶薄层分析板，在UV下检测，以及硫酸和磷钼酸的乙醇溶液浸润后加热显色。
核磁谱图由Bruker Advance 500(1H：500MHz，13C：125MHz)分析获得。以下缩写用于届时裂分情况，s代表singlet，d代表doublet，t代表triplet，q代表quartet，m代表multiplet，b代表broad。
本发明的实施例为：一种Icetexane型松香烷二萜的制备方法，如图1所示，包括以下步骤：
S1、甲基化：
Figure PCTCN2021099948-appb-000005
称取1.0g(3mmol)化合物1(鼠尾草酸)置于100mL圆底烧瓶中，加入12.5mL甲苯和2.5mL甲醇溶解，0℃下缓慢滴加3mL三甲基硅基重氮甲烷的正己烷溶液(2.0mol/L，6mmol)。TLC监测，反应完全后向反应液中滴加1mL冰醋酸，旋蒸除去反应溶剂，加入50mL饱和食盐水，用乙酸乙酯萃取3次，每次乙酸乙酯的用量为30ml，乙酸乙酯层用无水硫酸钠干燥，进行硅胶柱层析(PE(石油醚)与EA(丙烯酸乙酯)的体积比为10:1)，得到945mg中间体(黄色固体，产率91％)。
1H NMR(400MHz,CDCl 3)δ7.52(s,1H),6.59(s,1H),5.87(s,1H),3.71(s,3H),3.35(dd,J＝11.1,2.7Hz,1H),3.25(dt,J＝13.8,6.9Hz,1H),2.85(dd,J＝9.4,4.5Hz,2H),2.39–2.27(m,1H),1.94–1.87(m,1H),1.74(dt,J＝14.0,3.3Hz,1H),1.69–1.64(m,1H),1.61(dd,J＝12.7,1.9Hz,1H),1.54–1.47(m,1H),1.37(dd,J＝13.3,4.6Hz,1H),1.31(dd,J＝9.2,4.2Hz,1H),1.25(dd,J＝6.9,4.4Hz,6H),1.05(s,3H),0.84(s,3H).
S2、还原：
Figure PCTCN2021099948-appb-000006
称取228mg(6mmol)氢化铝锂置于干燥的两口瓶中，加入5mL无水四氢呋喃，0℃下滴加10mL溶解了692mg(2mmol)化合物2的无水四氢呋喃，N 2保护下回流。反应完全后，0℃下向反应液中缓慢加入十水合硫酸钠至没有气泡产生，反应液用硅藻土抽滤，滤液旋干后进行硅胶柱层析(PE与EA的体积比为10:1)，得到458mg中间体3(白色固体，产率72％)。
1H NMR(400MHz,DMSO)δ9.74(s,1H),7.52(s,1H),6.57(s,1H),6.35(s,1H),4.26(d,J＝10.0Hz,1H),3.72(d,J＝10.0Hz,1H),3.20(d,J＝13.7Hz,1H),3.09(dd,J＝13.8,6.9Hz,1H),2.74(dd,J＝8.7,3.7Hz,2H),1.74–1.60(m,2H),1.53–1.41(m,3H),1.24(d,J＝5.3Hz,2H),1.12(dd,J＝6.9,4.3Hz,6H),1.00(dd,J＝13.4,10.6Hz,1H),0.94(s,3H),0.88(s,3H).
S3、重排：
Figure PCTCN2021099948-appb-000007
称取636mg(2.0mmol)化合物3和786mg三苯基膦(3.0mmol)置于100mL干燥的圆底烧瓶中，加入20mL无水四氢呋喃溶解，0℃下滴加606mg DIAD(3.0mmol)。室温下反应10min左右。反应完全后，旋转蒸发蒸干反应液，进行硅胶柱层析(PE与EA的体积比为10:1)，得到552mg化合物4(棕色油状物，产率92％)。
1H NMR(400MHz,CDCl 3)δ6.54(s,1H),5.53(d,J＝3.1Hz,1H),5.17(d,J＝49.9Hz,2H),3.70(d,J＝15.0Hz,1H),3.16–3.04(m,2H),2.89–2.70(m,2H),2.09–1.91(m,3H),1.83(dd,J＝11.7,4.3Hz,1H),1.41–1.35(m,1H),1.27(dd,J＝6.9,4.3Hz,6H),1.23–1.16(m,1H),1.12(ddd,J＝12.9,6.1,2.4Hz,1H),0.94(s,3H),0.90(s,3H).
本发明的实施例还包括鼠李草酸的提纯，包括以下操作：
Figure PCTCN2021099948-appb-000008
室温条件下，将迷迭香提取物(60％，20g)溶于乙酸乙酯(500mL)中，搅拌下向其中慢慢加入石油醚(150mL)，室温条件下搅拌半小时后，滤除不溶物，收集滤液部分浓缩，再用乙醇重结晶即可得到高纯度鼠尾草酸(95％，9g)。
综上所述，本发明提供的Icetexane型松香烷二萜的制备方法，利用三苯基膦和偶氮试剂，将还原的鼠尾草酸衍生物高效、高选择性的制备了Icetexane型松香烷二萜；本发明制备方法具有选择性高，产率高，可规模化制备、关键步骤无需保护的特点，可广泛推广应用。
上面结合附图对本发明实施例作了详细说明，但是本发明不限于上述实施例，在所属技术领域普通技术人员所具备的知识范围内，还可以在不脱离本发明宗旨的前提下作出各种变化。此外，在不冲突的情况下，本发明的实施例及实施例中的特征可以相互组合。
以上所述仅为本发明的实施例，并非因此限制本发明的专利范围，凡是利用本发明说明书内容所作的等同变换，或直接或间接运用在相关的技术领域，均同理包括在本发明的专利保护范围内。

Claims (10)

  1. 一种Icetexane型松香烷二萜的制备方法，其特征在于：包括如下步骤：
    S1、甲基化：将鼠尾草酸添加至甲基化体系中，固液分离，收集固相得到中间体2；
    Figure PCTCN2021099948-appb-100001
    S2、还原：将所述中间体2添加至还原体系中，固液分离，收集固相得到中间体3；
    Figure PCTCN2021099948-appb-100002
    S3、重排：将所述中间体3添加至重排体系中，固液分离，收集固相得到所述Icetexane型松香烷二萜；
    Figure PCTCN2021099948-appb-100003
    其中，所述重排体系包括重排试剂和重排反应溶剂；
    所述重排试剂包括有机膦和偶氮试剂。
  2. 根据权利要求1所述的一种Icetexane型松香烷二萜的制备方法，其特征在于：所述制备方法还包括鼠尾草酸的分离纯化。
  3. 根据权利要求1所述的一种Icetexane型松香烷二萜的制备方法，其特征在于：所述甲基化体系包括甲基化试剂、碱和甲基化反应溶剂。
  4. 根据权利要求3所述的一种Icetexane型松香烷二萜的制备方法，其特征在于： 所述甲基化试剂为碘甲烷、硫酸二乙酯、重氮甲烷和三甲硅基重氮甲烷中的至少一种；优选地，所述碱为碳酸盐、三乙胺和4-二甲氨基吡啶中的至少一种；优选地，所述甲基化反应溶剂为丙酮、二甲基亚砜、二甲基甲酰胺、甲醇、四氢呋喃、甲苯和氯苯中的至少一种。
  5. 根据权利要求1所述的一种Icetexane型松香烷二萜的制备方法，其特征在于：所述还原体系包括还原试剂和还原反应溶剂。
  6. 根据权利要求5所述的一种Icetexane型松香烷二萜的制备方法，其特征在于：所述还原试剂为氢化锂铝、硼氢化钠、二异丁基氢化铝和二氢双(2-甲氧乙氧基)铝酸钠。
  7. 根据权利要求5所述的一种Icetexane型松香烷二萜的制备方法，其特征在于：所述还原反应溶剂为四氢呋喃、甲基四氢呋喃、乙醚、甲基叔丁基醚和甲苯中的至少一种。
  8. 根据权利要求1所述的一种Icetexane型松香烷二萜的制备方法，其特征在于：所述偶氮试剂为DIAD和DEAD中的至少一种；优选地，所述有机膦包括三苯基膦、三叔丁基膦、三环己基膦和联萘二苯基膦中的至少一种。
  9. 根据权利要求8所述的一种Icetexane型松香烷二萜的制备方法，其特征在于：有机膦和偶氮试剂的物质的量之比为0.5：1～5：1；优选地，所述中间体3在重排体系中浓度范围为0.01mol/L～5.0mol/L。
  10. 根据权利要求1所述的一种Icetexane型松香烷二萜的制备方法，其特征在于：所述重排反应溶剂为四氢呋喃、甲基四氢呋喃、1，4-二氧六环、乙醚、甲基叔丁基醚和甲苯中的至少一种。
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