WO2021249545A1

WO2021249545A1 - Method for one-step preparation of polyether having trans-fused polycyclic ether framework structure

Info

Publication number: WO2021249545A1
Application number: PCT/CN2021/099762
Authority: WO
Inventors: 渠瑾; 李风兴
Original assignee: 南开大学
Priority date: 2020-06-12
Filing date: 2021-06-11
Publication date: 2021-12-16
Also published as: CN113801128A

Abstract

The present invention provides a method for one-step preparation of polyether having a trans-fused polycyclic ether framework structure. In particular, the present invention provides a preparation method for a trans-fused polycyclic ether compound represented by formula (I), comprising the following steps: in the presence of a reaction medium and a salt containing a weakly coordinating anion, preparing a trans-fused polycyclic ether compound represented by formula (I) by subjecting a homochiral polyepoxy compound represented by formula (II) to a one-step cyclization reaction. The preparation method of the present invention has one or more advantages such as easy preparation of raw materials, short synthetic route, simple experimental operation, mild reaction conditions, rapid reaction and high yield.

Description

One-step method for preparing polyether with trans-fused polycyclic ether skeleton structure

Cross-references to related applications

This application claims the priority of the Chinese patent application 202010532858.8 whose filing date is 2020/06/12. This application quotes the full text of the aforementioned Chinese patent application.

Technical field

The invention relates to a one-step method for preparing a polyether with a trans-fused polycyclic ether skeleton structure.

Background technique

In 1981, the structure of the first marine polyether toxin brevetoxin B (brevetoxinB) was determined to be a polycyclic ether compound with 11 trans-fused cyclic ethers (J.Am.Chem.Soc.1981) , 103, pp 6773-6775). In the following years, scientists have discovered more than 50 marine polyether toxins from marine algae. The structural identification of these marine polyether toxins showed that these compounds all have similar trans-fused polycyclic ether skeleton structures in their molecules, that is, the molecules contain multiple trans-syn-trans relative three-dimensional configurations. The cyclic ether (the size of the cyclic ether is five-membered cyclic ether, six-membered cyclic ether, seven-membered cyclic ether, eight-membered cyclic ether, and nine-membered cyclic ether). Because it contains multiple fused cyclic ethers, marine polyether toxins The molecular skeleton of the product is in the shape of a ladder, so it is also known as a trapezoidal thick polyether toxin. The following figure lists the chemical structural formulas of typical marine polyether toxin brevetoxin B (brevetoxin B), hemibrevetoxin B, brevenal, brevetoxin A (brevetoxin A), and ciguatoxin 3C (ciguatoxin 3C) (Chem. Rev. 1993, 93, pp1897-1909).

Marine polyether toxins produced by marine algae generally have strong neurotoxicity. When marine algae multiply morbidly, the marine polyether toxins produced by them can cause a large number of deaths of marine organisms. Marine polyether toxins can also be concentrated in fish, shrimp or shellfish through the transmission of the food chain. If the contaminated fish, shrimp or shellfish is accidentally eaten by humans, it will cause a poisoning reaction, which can lead to death in severe cases (Toxicon 2001, 39). , Pp 97-106). But there are also some marine polyethers that have biological activity that can be developed as drugs (Chem. Res. Toxicol. 2004, 17, pp 1251-1257). Studies have shown that the marine polyether brevenal itself produced by the marine algae Karenia brevis It has no neurotoxicity, but has the biological activity of improving cystic fibrosis (Science 2007, 316, pp 1561-1562). Cystic fibrosis is a hereditary lung disease. The patient’s lungs Will be repeatedly infected by bacteria. There are more than 70,000 patients with cystic fibrosis in the world, and no effective treatment has yet been found. In 2018, brevenal was approved by the US FDA as an orphan drug to enter a phase I clinical trial for the treatment of cystic fibrosis. Recent studies on brevenal have shown that brevenal also has a potential therapeutic effect on other chronic lung diseases (Mar. Drugs 2019, 17, pp 184). Studies on brevenal also show that brevenal can also competitively bind to the protein receptors of breven pyridine toxin and ciguatoxin in the human body, thereby reducing the poisoning reaction caused by breven pyridine toxin and ciguatoxin (Cell.Mol .Neurobiol. 2004, 24, pp 553-563).

Although brevenal is a potential treatment option for chronic lung diseases such as cystic fibrosis, the daily use of brevenal or its derivatives will be very expensive for patients. The content of brevenal produced by Lusoflagellate is very low, and it is difficult to obtain large amounts of brevenal only by extraction. The brevenal containing the trans-fused 7/7/6/7/6 pentacyclic ether structure can also be obtained by artificial synthesis. At present, there are 6 total synthetic routes of brevenal that have been reported. In 2006, Sasaki, Tohoku University, Japan The professor’s group reported the total synthesis of brvenal for the first time. They used 2-deoxy-D-ribose as the starting material and used the Suzuki-Miyaura cross-coupling reaction to splice the AB and DE ring fragments of brvenal before constructing the C ring. , The subsequent introduction of the side chain through a series of transformations, the total number of steps in this route exceeds 50 steps (Figure a below, J.Am.Chem.Soc.2006, 128, pp 16989-16999); they reported the second-generation synthesis in 2008 The route requires 47 steps, with a total yield of 0.2% (Org.Lett.2008, 10, pp 2275-2278); in 2011, the team once again reported a more efficient third-generation with a total of 40 steps Synthetic route, the total yield is 2.26% (Chem.Eur.J.2011, 17, pp 13754-13761); in 2009, Professor Kadota's research group from Okayama University in Japan also reported the total synthesis of brevenal, their first generation The total synthesis route constructs the DE ring of brevenal through the intramolecular allylation reaction of α-chloroacetoxy ether and the subsequent ring-closure metathesis. The total yield of total synthesis of 57 steps is 0.84% (Figure b, Org. Lett. 2009, 11, pp 2531-2534); In 2010, the second-generation total synthesis route of Professor Kadota’s research group required 53 steps, with a total yield of 1.8% (Tetrahedron 2010, 66, pp 5329-5344) ; In 2011, Professor Rainier's research group from the University of Utah used the key enester cyclization reaction to achieve the construction of the two-ring CD of brevenal. Their total synthesis route of brevenal was 38 steps, and the total yield was 0.99% (Figure c below) , J. Am. Chem. Soc. 2011, 133, pp 3208-3216). Looking at the six total synthesis routes of brevenal, it can be found that if the trans-fused 7/7/6/7/6 pentacyclic ether skeleton structure in the brevenal molecule is constructed carbon by carbon and ring by ring, a very lengthy synthesis is required. Routes and expensive synthetic reagents.

In the 1980s, Japanese chemist Nakanishi noticed that every marine polyether toxin molecule contains a regular trans-fused polycyclic ether skeleton, although the number and size of the ring are different. The birth path of the student puts forward the famous Nakanishi conjecture (the figure below, Toxicon 1985, 23, pp 473-479). This conjecture speculates that a (R, R) selective cyclooxygenase catalyzes the asymmetric epoxidation reaction of long-chain polyene precursors, giving a long-chain polyepoxy with all (R, R) chirality The compound, and then the homochiral polyepoxy compound undergoes a one-step intramolecular endo, endo-selective series epoxy ring-opening and cyclization reaction, and a one-step reaction constructs 11 trans-fused cyclic ethers in brevetoxin B. If the backbone structure of the trans-fused polycyclic ether can be quickly constructed through the intra-molecular tandem reaction in the way Nakanishi conjectured, the synthesis of the marine polyether drug brevenal can be greatly simplified.

The precursor compound of the tandem reaction in Nakanishi's conjecture, long-chain polyepoxy compounds can be synthesized from long-chain polyene compounds by Shi asymmetric epoxidation in one step, and long-chain polyene compounds can be synthesized from commercially available small molecules. The raw materials are prepared by organic reactions such as Wittig reaction and transition metal-catalyzed coupling reaction, so the precursor compound of the tandem reaction is easy to prepare in organic synthesis, but it is a one-step series connection of long-chain homochiral polyepoxy precursors. The epoxy ring-opening and cyclization reaction to construct a marine polyether toxin with a trans-fused polycyclic ether skeleton, the Nakanishi conjecture, has still not been realized. This is because according to the empirical rules of Baldwin intramolecular cyclization reaction, when a single cyclic ether is generated from the intramolecular monoepoxy ring-opening and cyclization reaction, it tends to form a smaller five-membered cyclic ether in the exo mode, and the ring in the endo mode. The formation of six-membered cyclic ethers is energy unfavorable (Figure a below, J. Chem. Soc. Chem. Commun. 1976, pp734-736). The key tandem cyclization proposed in the Nakanishi conjecture is carried out by intramolecular endo, endo- tandem epoxy ring-opening cyclization. According to the Baldwin rule, endo-selective tandem epoxy ring-opening cyclization is relatively exo, exo -Tandem epoxy ring-opening and cyclization is unfavorable in terms of energy, and only polyepoxy compound endo, endo-selective tandem epoxy ring-opening and cyclization can generate trans-fused polycyclic ether structure, exo, The exo-series epoxy ring-opening cyclization produces a non-condensed polycyclic ether structure connected by a single carbon-carbon bond (Figure b below).

At present, in this extremely challenging research field, there are 3 cases reported that the trans-fused polycyclic ether can be constructed through the intramolecular endo, endo-selective series epoxy ring-opening and cyclization reaction of the polyepoxy precursor compound. structure. In 2000, the Murai research group in Japan developed the intramolecular endo, endo-selective tandem epoxy ring-opening and cyclization reaction of homochiral polyepoxy precursor compounds catalyzed by lanthanum salt. The introduction of a methoxymethyl group into the exo cyclization site of an epoxy can achieve better endo selectivity, but the yield of the polyether product containing three trans-fused six-membered rings is only 9% (Synlett 2000, pp 335-338).

In 2002, the McDonald research group in the United States found that when the homochiral polyepoxy precursor compound has a carbonyl group instead of a hydroxyl group as the terminating group, the polyepoxy precursor compound can undergo intramolecular endo, endo-selection under the catalysis of Lewis acid. The serial epoxy ring-opening and cyclization reaction realizes the construction of polyethers in which all the trans-fused cyclic ethers are seven-membered rings. The yield of polyethers containing four seven-membered rings is only 12% (J. Org. Chem. 2002, 67, pp 2515-2523).

In 2007, Jamison’s research group discovered that a tetrahydropyran ring was placed in advance at one end of a long-chain homochiral polyepoxy substrate as a guiding structure. In hot water, the polyepoxy substrate can undergo intramolecular endo, endo-selection. The serial epoxy ring-opening and cyclization reaction produces a trans-fused polyether whose all cyclic ethers are six-membered rings. The yield of polyethers containing four six-membered rings is 53% (Science 2007, 317, pp 1189-1192).

The yields of the first two cases of these 3 cases are low, and these 3 cases can only produce all six-membered ring polyethers or all seven-membered ring polyethers, while the biologically active marine polyether toxin brevenal molecule It has a 7/7/6/7/6 five-ring structure mixed with six-membered cyclic ether and seven-membered cyclic ether. In addition, many biologically active marine polyether toxins contain eight-membered cyclic ethers or nine-membered cyclic ethers. The existing endo, endo-selective tandem epoxy ring-opening and cyclization method cannot be used to synthesize molecules containing eight-membered cyclic ethers. Cyclic ethers or polyethers of nine-membered cyclic ethers.

Summary of the invention

The technical problem to be solved by the present invention is that the preparation method of polyether with trans-fused polycyclic ether skeleton structure in the prior art is relatively simple, thereby providing a new one-step method for preparing polyether with trans-fused polycyclic ether skeleton Structured polyether (trans-fused polycyclic polyether) method. This method uses easy-to-prepare long-chain homochiral polyepoxy compounds as raw materials, and can synthesize trans-fused polycyclic ether compounds through a one-step intramolecular endo, endo-selective serial epoxy ring-opening and cyclization reaction. The cyclic ether in the formed polycyclic ether compound may be a six-membered cyclic ether, a seven-membered cyclic ether, an eight-membered cyclic ether, a nine-membered cyclic ether, or a combination thereof.

The present invention provides a method for preparing a trans-fused polycyclic ether compound represented by formula (I), which comprises the following steps: in the presence of a reaction medium and a salt containing a weak coordination anion, the formula (II) The homochiral polyepoxy compound shown is prepared by a one-step cyclization reaction to obtain the trans-fused polycyclic ether compound represented by formula (I);

(The subscripts u, v, x and y are used to indicate the structure of the fragment, *, # and & are used to indicate the carbon atom and have no other meaning)

Among them, in the trans-fused polycyclic ether compound represented by formula (I) and the homochiral polyepoxy compound represented by formula (II):

Each R is the same or different, and is independently selected from H, C _1-3 alkyl- or halogenated C _1-3 alkyl-; particularly preferably H, methyl, ethyl, propyl or isopropyl; most preferably H Or methyl

Each R _{1 is the} same or different, and is independently selected from H, C _1-10 alkyl-, C _1-10 alkyl-OC _1-10 alkyl-, C _6-10 aryl-C _1-10 alkyl- OC _1-10 alkyl-, halogenated C _1-10 alkyl-; preferably H, C _1-6 alkyl-, C _1-6 alkyl-OC _1-6 alkyl-, C _6-10 aryl -C _1-6 alkyl-OC _1-6 alkyl-, halogenated C _1-6 alkyl-; more preferably H, C _1-3 alkyl-, C _1-3 alkyl-OC _1-3 alkane Group-, phenyl-C _1-3 alkyl-OC _1-3 alkyl-, halogenated C _1-3 alkyl-; particularly preferably H, methyl, ethyl, propyl, isopropyl; most preferably H. Methyl;

Each R _{2 is the} same or different, and is independently selected from H, C _1-10 alkyl-, C _1-10 alkyl-OC _1-10 alkyl-, C _6-10 aryl-C _1-10 alkyl- OC _1-10 alkyl-, halogenated C _1-10 alkyl-; preferably H, C _1-6 alkyl-, C _1-6 alkyl-OC _1-6 alkyl-, C _6-10 aryl -C _1-6 alkyl-OC _1-6 alkyl-, halogenated C _1-6 alkyl-; more preferably H, C _1-3 alkyl-, C _1-3 alkyl-OC _1-3 alkane Group-, phenyl-C _1-3 alkyl-OC _1-3 alkyl-, halogenated C _1-3 alkyl-; particularly preferably H, methyl, ethyl, propyl, isopropyl; most preferably H, methyl; or, when R ₂ is connected to a double-bonded carbon atom, R ₂ does not exist;

Each n is the same or different, and is independently selected from 1, 2, 3, 4;

The carbon atoms in the fragments can be optionally substituted by the following groups: H, OH, C _1-4 alkyl- or halogenated C _1-4 alkyl-;

When n=2 or 3 or 4, where appropriate, the polyether compound of formula (I) and the polyepoxy compound of formula (II) optionally form a C=C double between adjacent two carbon atoms The position of the C=C double bond in the polyepoxy compound of formula (II) corresponds to the position of the C=C double bond in the polyether compound of formula (I) as the product;

R ₃ is H or an acid-sensitive hydroxyl protecting group; the acid-sensitive hydroxyl protecting group is for example an ether protecting group (such as THP (2-tetrahydropyranyl)), a silyl ether protecting group (such as TMS (three Methylsilyl) or TES (triethylsilyl)), preferably THP, TMS, most preferably THP;

In the trans-fused polycyclic ether compound represented by formula (I),

The part represents the structure in which the x fragments and the y fragments appear alternately and repeatedly. The number of x fragments in the structure of formula (I) is Nx≥1, and Nx can specifically be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11; the number of y fragments Ny≥0, Ny can specifically be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; and 1≤Nx+Ny≤20, preferably 1≤Nx +Ny≤15, more preferably 1≤Nx+Ny≤10, particularly preferably 1≤Nx+Ny≤8 (for example, Nx+Ny=1, 2, 3, 4, 5, 6, 7 or 8), most preferably 1 ≤Nx+Ny≤4 (for example, Nx+Ny=1, 2, 3 or 4);

In the homochiral polyepoxy compound represented by formula (II),

The part represents the structure in which u fragments and v fragments appear alternately and repeatedly, the number of u fragments in the entire structure of formula (II) is Nu≥1, and Nu can specifically be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11; the number of v fragments Nv≥0, Nv can specifically be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; and 1≤Nu+Nv≤20, preferably 1≤Nu +Nv≤15, more preferably 1≤Nu+Nv≤10, particularly preferably 1≤Nu+Nv≤8 (for example, Nu+Nv=1, 2, 3, 4, 5, 6, 7 or 8), most preferably 1 ≤Nu+Nv≤4 (for example, Nu+Nv=1, 2, 3 or 4);

In the same reaction, Nx+Ny=Nu+Nv.

In order to facilitate the understanding of the present invention, further

The fragment description is as follows: In the trans-fused polycyclic ether compound represented by formula (I), when Nx+Ny=1, then the y fragment and

Part is not present; when Nx+Ny=2, then

Part is not present; when Nx+Ny=3, then

Part is x fragment; when Nx+Ny=4, then

Part of it is an xy segment; when Nx+Ny=5, then

Part is xyx fragment; when Nx+Ny=6, then

Part is xyxy fragment; and so on.

In order to facilitate the understanding of the present invention, further

The fragment description is as follows: in the homochiral polyepoxy compound of formula (II), when Nu+Nv=1, then the v fragment and

Part is not present; when Nu+Nv=2, then

Part is not present; when Nu+Nv=3, then

Part is u fragment; that is, when Nu+Nv=4, then

Part is uv fragment; when Nu+Nv=5, then

Part is uvu fragment; when Nu+Nv=6, then

Some are uvuv fragments; and so on.

Those skilled in the art can understand that in the structures of formula (I) and formula (II), the number of u fragments Nu=the number of x fragments Nx, and the number of v fragments Nv=the number of y fragments Ny.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound, the structures of the trans-fused polycyclic ether compound and the homochiral polyepoxy compound are defined as follows:

Wherein, in the polyether compound of formula (I) and the polyepoxy compound of formula (II), each R is the same or different, and is independently selected from H, C _1-3 alkyl-, halogenated C _1-3 alkane Group -; H, methyl, ethyl, propyl, isopropyl are particularly preferred; H, methyl is most preferred.

Each n is the same or different, and is independently selected from 1, 2, 3; or

When n=2 or 3, where appropriate, the polyether compound of formula (I) and the polyepoxy compound of formula (II) optionally form a C=C double bond between two adjacent carbon atoms, And the position of the C=C double bond in the polyepoxy compound of formula (II) corresponds to the position of the C=C double bond in the polyether compound of formula (I) as the product;

In the polyether compound of formula (I) and the polyepoxy compound of formula (II),

The carbon atoms in the fragment can be optionally substituted by the following groups: H, OH, C _1-4 alkyl-, halo C _1-4 alkyl-; or

In the polyether compound of formula (I),

The part represents the structure where x fragments and y fragments appear alternately and repeatedly, the number of x fragments in the molecule of formula (I) is Nx≥1, and Nx can specifically be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11; the number of y fragments Ny≥0, Ny can specifically be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; and 1≤Nx+Ny≤20, preferably 1≤Nx +Ny≤15, more preferably 1≤Nx+Ny≤10, particularly preferably 1≤Nx+Ny≤8 (for example, Nx+Ny=1, 2, 3, 4, 5, 6, 7 or 8), most preferably 1 ≤Nx+Ny≤4 (for example, Nx+Ny=1, 2, 3, or 4).

In the polyepoxy compound of formula (II),

The part represents the structure where u fragments and v fragments appear alternately and repeatedly, the number of u fragments in the entire formula (II) molecule is Nu≥1, and Nu can be specifically 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11; the number of v fragments Nv≥0, Nv can specifically be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; and 1≤Nu+Nv≤20, preferably 1≤Nu +Nv≤15, more preferably 1≤Nu+Nv≤10, particularly preferably 1≤Nu+Nv≤8 (for example, Nu+Nv=1, 2, 3, 4, 5, 6, 7 or 8), most preferably 1 ≤Nu+Nv≤4 (for example, Nu+Nv=1, 2, 3, or 4).

And in the same reaction, Nx+Ny=Nu+Nv.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound, the structure of the trans-fused polycyclic ether compound represented by formula (I) and the polyepoxy compound of formula (II) as follows:

The definition of each variable is as described in any of the aforementioned schemes.

In some embodiments, in some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any of the foregoing embodiments, the

Structure is

(I.e. form with the structure on the right

), where the a terminal is connected to the epoxy group, and the b terminal is connected to the carbon atom marked with &; others

The structure is the same or different, which are independently

The c terminal is connected to the left group, and the d terminal is connected to the right group;

Each hydrogen atom in the structure is independently optionally _{substituted by R 4} ; R _{4 is} independently OH, C _1-4 alkyl- or halogenated C _1-4 alkyl-, preferably methyl, ethyl, propyl , Isopropyl, most preferably methyl.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding embodiments, each n is the same or different, and is independently selected from 1, 2 or 3. .

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding embodiments, R ₃ is H.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding embodiments, R ₃ is an acid-sensitive hydroxyl protecting group, such as an ether protecting group The group (for example, THP (2-tetrahydropyranyl)) and the silyl ether protecting group (for example, TMS (trimethylsilyl) or TES (triethylsilyl)) are preferably THP, TMS, and most preferably THP.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any of the foregoing embodiments, the R connected to the carbon atom marked with * is a C _1-3 alkane Group-, preferably methyl, ethyl, propyl, isopropyl, most preferably methyl.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding embodiments, R ₁ connected to the carbon atom marked with * is C _1-10 Alkyl-, preferably C _1-6 alkyl-, more preferably C _1-3 alkyl-, particularly preferably methyl, ethyl, propyl, isopropyl, and most preferably methyl.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any of the foregoing embodiments, R and R ₁ connected to the carbon atom marked with * are the same .

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any of the foregoing embodiments, R and R ₁ connected to the carbon atom marked with * are both methyl base.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding embodiments, R in the u, v, x, and y fragments are independently H Or C _1-3 alkyl-, particularly preferably H, methyl, ethyl, propyl or isopropyl, most preferably H or methyl.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding embodiments, the

Structure is

The a terminal is connected to the epoxy group, and the b terminal is connected to the carbon atom marked with &; others

The structure is the same or different, which are independently

Above

Each hydrogen atom in the structure is independently optionally substituted _{by R 4.}

Structure is

The structure is the same or different, which are independently

Above

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding schemes, the leftmost compound of the general formula

structure

Above

Each hydrogen atom in the structure is independently optionally _{substituted by R 4} ; R _{4 is} independently OH, C _1-4 alkyl- or halogenated C _1-4 alkyl-, preferably C _1-3 alkyl-, Particularly preferred are methyl, ethyl, propyl, and isopropyl, and most preferred are OH and methyl.

Structure is

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding embodiments, in the adjacent x and y fragments

The n in the structure is different.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding embodiments, R ₂ is H or C _1-10 alkyl-, preferably H Or C _1-6 alkyl-, more preferably H or C _1-3 alkyl-, particularly preferably H, methyl, ethyl, propyl or isopropyl, most preferably H or methyl; or, & marked When a double bond is connected to the carbon atom, R ₂ connected to the carbon atom marked with & does not exist.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding embodiments, R ₂ connected to the carbon atom labeled & is H, or, When a double bond is connected to the carbon atom labeled &, R ₂ connected to the carbon atom labeled & does not exist.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding embodiments, the R connected to the carbon atom labeled & is H or C _{1- 3} Alkyl-, preferably H, methyl, ethyl, propyl or isopropyl, most preferably H or methyl, such as H.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any of the foregoing embodiments, R ₂ and R connected to the carbon atom labeled & are H, Alternatively, when a double bond is connected to the carbon atom labeled &, R ₂ connected to the carbon atom labeled & does not exist.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding schemes, the R connected to the carbon atom marked with # is H or C _{1- 3} Alkyl-, preferably H, methyl, ethyl, propyl or isopropyl, most preferably H or methyl.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any one of the preceding embodiments, R ₂ connected to the carbon atom marked with # is H or C _{1 -10} alkyl-, preferably H or C _1-6 alkyl-, more preferably H or C _1-3 alkyl-, particularly preferably H, methyl, ethyl, propyl or isopropyl, most preferably H or methyl.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any of the foregoing embodiments, R ₂ and R connected to the carbon atom labeled with # are the same .

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound represented by formula (I) as described in any of the foregoing embodiments, R ₂ and R connected to the carbon atom labeled with # are the same And is H or methyl.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound, the structures of the trans-fused polycyclic ether compound and the polyepoxy compound are as follows:

Wherein, R, R ₁ , R ₂ , R ₃ , and n are defined as described in any of the above schemes.

Among them, R, R ₁ , R ₂ , R ₃ , n,

The definition is as described in any of the above schemes.

Among them, R, R ₁ , R ₂ , R ₃ , n,

The definition is as described in any of the above schemes;

Preferably,

for

For example

Wherein, R, R ₁ , R ₂ , R ₃ , and n are as defined above.

Among them, R, R ₁ , R ₂ , R ₃ , n,

The definition is as described in any of the above schemes.

Among them, R, R ₁ , R ₂ , R ₃ , n,

The definition is as described in any of the above schemes;

Preferably,

The structure is independently

Further preferably, in the u and x fragments

Structure is

Further preferably, the leftmost of the general formula

Structure is

Wherein, the definitions of R, R ₁ , R ₂ , R ₃ , and n are as described in any of the above schemes.

Among them, R, R ₁ , R ₂ , R ₃ , n,

The definition is as described in any of the above schemes.

Among them, R, R ₁ , R ₂ , R ₃ , n,

The definition is as described in any of the above schemes;

Preferably,

The structure is independently

Further preferably, in the u and x fragments

Structure is

Further preferably, in the v and y fragments

Structure is

Further preferably, the leftmost of the general formula

Structure is

Among them, R, R ₁ , R ₂ , R ₃ , n,

The definition is as described in any of the above schemes;

Preferably,

The structure is independently

Further preferably, in the u and x fragments

Structure is

Further preferably, in the v and y fragments

Structure is

Further preferably, the leftmost of the general formula

Structure is

Among them, R, R ₁ , R ₂ , R ₃ , n,

The definition is as described in any of the above schemes.

Among them, R, R ₁ , R ₂ , R ₃ , n,

The definition is as described in any of the above schemes;

Preferably,

The structure is independently

Further preferably, in the u and x fragments

Structure is

Further preferably, in the v and y fragments

Structure is

Further preferably, the leftmost of the general formula

Structure is

R in the u, v, x and y fragments are independently H or methyl;

Connected to the & marked carbon atom

Structure is

The structure is the same or different, which are independently

_{R 2} and R connected to the carbon atom marked with # are the same and are H or methyl;

_{R 2} connected to the carbon atom labeled & is H, or when a double bond is connected to the carbon atom labeled &, R ₂ connected to the carbon atom labeled & does not exist.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound, the structure of the trans-fused polycyclic ether compound and the polyepoxy compound is any one of the following groups:

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound as described in any of the above embodiments, the reaction medium may be a C _1-10 alkyl alcohol substituted by one or more halogens or its Mixed solvent with other solvents. _{Among them, the C 1-10} alkyl alcohol substituted by one or more halogens _{is preferably C 1-8} alkyl alcohol substituted by one or more halogens _{, more preferably C 1} substituted by one or more halogens. _-6 alkyl alcohol, particularly preferably a C _1-4 alkyl alcohol substituted by one or more halogens; wherein the halogen is selected from fluorine, chlorine, bromine, and iodine. The other solvent may be selected from C _1-10 _{alkanes substituted with one or more halogens, C 1-10} ethers or cyclic ethers optionally substituted with one or more halogens, C 1-10 optionally substituted with one or more halogens _1-10 esters; preferably chloroform, dichloromethane, 1,2-dichloroethane, 1,1-dichloroethane ethyl ether, tetrahydrofuran, 1,4-dioxane.

In some embodiments, in the preparation method of the trans-fused polycyclic ether compound as described in any of the above embodiments, the reaction medium is most preferably trifluoromethanol, trifluoroethanol, perfluoroethanol, trifluoropropanol (Including n-propanol, isopropanol), hexafluoropropanol (including n-propanol, isopropanol), perfluoropropanol (including n-propanol, isopropanol), trifluorobutanol (including n-butanol) , Isobutanol, tert-butanol), hexafluorobutanol (including n-butanol, isobutanol, tert-butanol), perfluorobutanol (including n-butanol, isobutanol, tert-butanol), trifluorobutanol Pentanol (including n-pentanol, isoamyl alcohol, tert-amyl alcohol, neopentyl alcohol), hexafluoropentanol (including n-pentanol, isoamyl alcohol, tert-amyl alcohol, neopentyl alcohol), perfluoropentanol (including N-pentanol, isoamyl alcohol, tert-amyl alcohol, neopentyl alcohol), trifluorohexanol, hexafluorohexanol, perfluorohexanol. In some embodiments, the reaction medium may specifically be 2,2,2-trifluoroethanol (TFE), 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), perfluoro tertiary Butanol (PFTB), most preferably perfluoro-tert-butanol (PFTB).

The weakly coordinating anion-containing salt is soluble in the reaction medium.

In some embodiments, the anionic salt containing weakly coordinating anion is preferably a fluorine-containing weakly coordinating anion, it may be: tetrafluoroborate anion (BF ₄ ^-), hexafluorophosphate anion (PF ₆ ^-), six hexafluoro antimonate anion (SbF ₆ ^-), trifluoromethanesulfonic acid anion (trifluoromethansulfonate, TfO-), tetrakis [3,5-bis (trifluoromethyl) phenyl] borate anion (tetrakis [3,5-bis ( trifluoromethyl) phenyl] borate, (BARF )), tetrakis (pentafluorophenyl) borate anion (tetrakis (pentafluorophenyl) borate); preferably tetrafluoroborate anion (BF ₄ ^-), hexafluorophosphate anion (PF ₆ ^-); most tetrafluoroborate anion (BF ₄ ^-).

In some embodiments, the cation of the salt containing weak coordination anion can be selected from quaternary ammonium ion or quaternary phosphorus ion, for example, tetramethylammonium ion (Me ₄ N ⁺ ), tetraethylammonium ion (Et ₄ N ⁺ ), tetra-n-butylammonium ion ((n-Bu) ₄ N ⁺ ), tetraphenyl quaternary phosphonium ion (Ph ₄ P ⁺ ), 1-butyl-3-methylimidazole quaternary ammonium ion ([BMIM]) , 1-ethyl-3-methylimidazole quaternary ammonium ion ([EMIM]), 1-hexyl-3-methylimidazole quaternary ammonium ion ([HMIM]); preferably 1-butyl-3-methylimidazole quaternary Ammonium ion ([BMIM]), 1-ethyl-3-methylimidazole quaternary ammonium ion ([EMIM]); more preferably 1-ethyl-3-methylimidazole quaternary ammonium ion ([EMIM]).

In some embodiments, the salt containing weak coordination anions may specifically be [BMIM]BF ₄ , [BMIM]PF ₆ , [EMIM]BF ₄ , [EMIM]PF ₆ , [HMIM]BF ₄ , [HMIM ]PF ₆ ; preferably [BMIM]BF ₄ , [EMIM]BF ₄ , [HMIM]BF ₄ ; more preferably [EMIM]BF ₄ .

In some embodiments, the molar ratio of the salt containing the weakly coordinating anion to the homochiral polyepoxy compound represented by formula (II) may be 1:10-10:1, preferably 1:5-5:1, It is more preferably 1:2 to 2:1, most preferably 1:1.

In some embodiments, the concentration of the homochiral polyepoxy compound represented by formula (II) in the cyclization reaction solution may be 0.01-2.0 mol/L, preferably 0.01-1.0 mol/L, more preferably 0.05 -0.5mol/L, most preferably 0.1-0.3mol/L.

In some embodiments, the cyclization reaction can be carried out at 0-100°C (preferably 10-60°C; more preferably 20-45°C; most preferably 40°C).

In some embodiments, the cyclization reaction time may be 0.5-24 hours, preferably 1-18 hours, more preferably 5-18 hours, particularly preferably 12-18 hours, and most preferably 15 hours.

definition

Those skilled in the art can understand that in the structure of the compound of the present invention,

Indicates the relative three-dimensional configuration.

Can be

when

for

时, then

for

when

for

时, then

for

In the present invention, halogen means fluorine, chlorine, bromine or iodine.

Alkyl represents a straight or branched chain saturated hydrocarbon group containing 1-10 carbon atoms; preferably a straight or branched chain saturated hydrocarbon group containing 1-8 carbon atoms; more preferably a straight chain or branched chain containing 1 to 6 carbon atoms Chain saturated hydrocarbon groups; most preferably straight or branched chain saturated hydrocarbon groups having 1 to 4 carbon atoms. Examples of alkyl groups include methyl, ethyl, propyl (including n-propyl, isopropyl), butyl (including n-butyl, isobutyl, tert-butyl), pentyl (including n-pentyl, isopropyl), Pentyl, tert-pentyl, neopentyl) or hexyl, etc.

Alkyl alcohol means a compound in which one or more H atoms in the above-mentioned alkyl group is substituted by OH. Examples of alkyl alcohols include methanol, ethanol, propanol (including n-propanol, isopropanol), butanol (including n-butanol, isobutanol, tert-butanol), pentanol (including n-pentanol, isoamyl alcohol) Alcohol, tert-amyl alcohol, neopentyl alcohol) or hexanol, etc.

Halohydrin refers to a compound in which one or more H atoms in the above-mentioned alkyl alcohol is substituted by halogen; wherein polyhalo refers to 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 15 or more halogens are substituted. Polyhalogenation also means that all H on the alkyl group in the alkyl alcohol is substituted by halogen. Examples of halogenated alcohols include trifluoromethanol, trifluoroethanol, perfluoroethanol, trifluoropropanol (including n-propanol, isopropanol), hexafluoropropanol (including n-propanol, isopropanol), perfluoropropanol Propanol (including n-propanol, isopropanol), trifluorobutanol (including n-butanol, isobutanol, tert-butanol), hexafluorobutanol (including n-butanol, isobutanol, tert-butanol) , Perfluorobutanol (including n-butanol, isobutanol, tert-butanol), trifluoropentanol (including n-pentanol, isoamyl alcohol, tert-amyl alcohol, neopentanol), hexafluoropentanol (including n-pentanol, Amyl alcohol, isoamyl alcohol, tert-amyl alcohol, neopentyl alcohol), perfluoropentanol (including n-amyl alcohol, isoamyl alcohol, tert-amyl alcohol, neopentyl alcohol) and trifluorohexanol, hexafluorohexanol, all Fluorohexanol, etc.; preferably trifluoroethanol, hexafluoropropanol, perfluorobutanol; most preferably 2,2,2-trifluoroethanol (TFE), 1,1,1,3,3,3-hexafluoro- 2-Propanol (HFIP), perfluoro-tert-butanol (PFTB).

The weakly coordinating anions (weakly coordinating anions) refer to a type of anion that has a very weak interaction force with the cation. Formula fused with polycyclic ether backbone polyether.

On the basis of not violating common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain preferred examples of the present invention.

The reagents and raw materials used in the present invention are all commercially available.

Beneficial effect

The preparation method of the invention has one or more advantages such as easy preparation of raw materials, short synthetic route, simple experimental operation, mild reaction conditions, rapid reaction and high yield. For example. The preparation method of the present invention can obtain a polyether with 2 trans-fused cyclic ethers at a yield of up to 55%, and obtain a polyether with 3 trans-fused cyclic ethers at a yield of up to 57%, A polyether with 4 trans-fused cyclic ethers was obtained at a yield of up to 40%, and a polyether with an eight-membered ring and 4 trans-fused cyclic ethers was obtained at a yield of up to 19%. The yield is as high as 17% to obtain the polyether with the trans-fused 7/7/6/7/6 pentacyclic ether skeleton in the brevenal molecule, and all the above-mentioned synthesis reactions only have one step. Compared with the existing multi-step organic synthesis method, the present invention provides a simpler synthetic route for the industrial synthesis of polyethers with trans-fused polycyclic ether skeletons, which has significant social and economic effects, and can be industrialized. The potential is high.

Description of the drawings

FIG. 1 is a hydrogen nuclear magnetic resonance spectrum of a polyether with two trans-fused cyclic ethers obtained in Example 1. FIG.

2 is a carbon nuclear magnetic resonance spectrum of the polyether with two trans-fused cyclic ethers obtained in Example 1. FIG.

3 is a hydrogen nuclear magnetic resonance spectrum of the polyether with 3 trans-fused cyclic ethers obtained in Example 2. FIG.

4 is a carbon nuclear magnetic resonance spectrum of the polyether with 3 trans-fused cyclic ethers obtained in Example 2. FIG.

5 is a hydrogen nuclear magnetic resonance spectrum of the polyether with 4 trans-fused cyclic ethers obtained in Example 3. FIG.

6 is a carbon nuclear magnetic resonance spectrum of the polyether with 4 trans-fused cyclic ethers obtained in Example 3. FIG.

7 is a high-resolution mass spectrum of the polyether with 4 trans-fused cyclic ethers obtained in Example 3. FIG.

FIG. 8 is a hydrogen nuclear magnetic resonance spectrum of a polyether containing an eight-membered ring and having 4 trans-fused cyclic ethers obtained in Example 4. FIG.

9 is a carbon nuclear magnetic resonance spectrum of a polyether containing an eight-membered ring and having 4 trans-fused cyclic ethers obtained in Example 4. FIG.

10 is a high-resolution mass spectrum of a polyether containing an eight-membered ring and having 4 trans-fused cyclic ethers obtained in Example 4. FIG.

11 is a hydrogen nuclear magnetic resonance spectrum of the polyether having a trans-fused 7/7/6/7/6 pentacyclic ether skeleton in the brevenal molecule obtained in Example 5. FIG.

Fig. 12 is a carbon nuclear magnetic resonance spectrum of the polyether having a trans-fused 7/7/6/7/6 pentacyclic ether skeleton in the brevenal molecule obtained in Example 5.

13 is a high-resolution mass spectrum of the polyether having a trans-fused 7/7/6/7/6 pentacyclic ether skeleton in the brevenal molecule obtained in Example 5.

14 is a hydrogen nuclear magnetic resonance spectrum of the polyether with 3 trans-fused cyclic ethers obtained in Example 6. FIG.

15 is a carbon nuclear magnetic resonance spectrum of the polyether with 3 trans-fused cyclic ethers obtained in Example 6. FIG.

16 is a high-resolution mass spectrum of the polyether with 3 trans-fused cyclic ethers obtained in Example 6. FIG.

FIG. 17 is a hydrogen nuclear magnetic resonance spectrum of the polyether with 3 trans-fused cyclic ethers obtained in Example 7. FIG.

18 is a carbon nuclear magnetic resonance spectrum of the polyether with 3 trans-fused cyclic ethers obtained in Example 7. FIG.

19 is a high-resolution mass spectrum of the polyether with 3 trans-fused cyclic ethers obtained in Example 7. FIG.

20 is a hydrogen nuclear magnetic resonance spectrum of the polyether with 4 trans-fused cyclic ethers obtained in Example 8. FIG.

21 is a carbon nuclear magnetic resonance spectrum of the polyether with 4 trans-fused cyclic ethers obtained in Example 8. FIG.

22 is a high-resolution mass spectrum of the polyether with 4 trans-fused cyclic ethers obtained in Example 8. FIG.

FIG. 23 is a hydrogen nuclear magnetic resonance spectrum of the polyether with 4 trans-fused cyclic ethers obtained in Example 9. FIG.

24 is a carbon nuclear magnetic resonance spectrum of the polyether with 4 trans-fused cyclic ethers obtained in Example 9. FIG.

25 is a high-resolution mass spectrum of the polyether with 4 trans-fused cyclic ethers obtained in Example 9.

detailed description

The present invention will be further described below in conjunction with specific embodiments to help the understanding of the present invention, but the protection scope of the present invention is not limited to the following embodiments.

The epoxidized compounds used in the examples of this application are all prepared from the corresponding olefinic compounds through the Shi asymmetric epoxidation reaction known in the art (for details, please refer to the document Angew.Chem.Int.Ed.2020, 59, pp 18473 -18478.; Org. Lett. 2012, 14, pp 3932-3935; Science 2007, 317, pp 1189-1192; J. Am. Chem. Soc. 2005, 127, pp 4586-4587), in which Shi asymmetric ring The oxidation reaction conditions are all conventional reaction conditions in the art.

Example 1:

The diastereomer mixture of diepoxy alcohol obtained by Shi asymmetric epoxidation (48.4 mg, 0.2 mmol, according to the hydrogen nuclear magnetic spectrum analysis, the content of all diepoxy alcohols (R, R) is 89%, That is, 0.178mmol) was dissolved in perfluoro-tert-butanol (2mL), then 1-ethyl-3-methylimidazole tetrafluoroborate (40mg, 0.2mmol) was added to it, and the reaction was stirred at 40°C for 15 hours . After the reaction was completed, water (5mL) was added to quench the reaction. The reaction mixture was extracted three times with dichloromethane, 10mL each time. The organic phases from the three extractions were combined. The organic phase was washed once with water (10mL) and then with brine (10mL) once. , And then dried with anhydrous magnesium sulfate, filtered and concentrated, using 35-50% ethyl acetate/petroleum ether as the eluent for silica gel column chromatography, separated to obtain a white solid (23.7mg, yield 55%), which is A trans-fused polycyclic ether with 2 rings. After ¹ H NMR, ¹³ C NMR and mass spectrometry analysis, the obtained proton nuclear magnetic resonance spectrum is shown in Fig. 1, and the carbon nuclear magnetic resonance spectrum is shown in Fig. 2.

Analytical data of polyether with 2 trans-fused cyclic ethers:

¹ H NMR (400MHz, CDCl ₃ ) δ 3.81 (dd, J = 6.3, 4.1 Hz, 1H), 3.64 (dd, J = 11.7, 4.4 Hz, 1H), 1.93-1.78 (m, 3H), 1.71 1.65(m, 1H), 1.62-1.56(m, 2H), 1.56-1.45(m, 2H), 1.28(s, 3H), 1.25(s, 3H), 1.24(s, 3H), 1.18(s, 3H), 1.12(s, 3H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 78.1, 76.6, 76.5, 73.5, 71.0, 37.3, 36.2, 33.2, 28.8, 27.2, 25.5, 25.0, 22.1, 19.9;

HRMS(ESI): m/z C ₁₄ H ₂₇ O ₃ [M+H] ⁺ calculated value 243, 1955, measured value 243.1957.

Example 2:

The diastereomer mixture of triepoxy alcohol obtained by Shi asymmetric epoxidation (59.6mg, 0.2mmol, according to the hydrogen nuclear magnetic spectrum analysis, the content of the substrate of triepoxy alcohol which is all (R, R) is 83%, ie 0.166mmol) was dissolved in perfluoro-tert-butanol (2mL), then 1-ethyl-3-methylimidazole tetrafluoroborate (40mg, 0.2mmol) was added to it, and stirred at 40°C React for 15 hours. After the reaction was completed, water (5mL) was added to quench the reaction. The reaction mixture was extracted three times with dichloromethane, 10mL each time. The organic phases from the three extractions were combined. The organic phase was washed once with water (10mL) and then with brine (10mL) once. , And then dried with anhydrous magnesium sulfate, filtered and concentrated, using 35-50% ethyl acetate/petroleum ether as the eluent for silica gel column chromatography, separated to obtain a white solid (28.2mg, yield 57%), which is 3-ring trans-fused polycyclic ether. After ¹ H NMR, ¹³ C NMR and mass spectrometry analysis, the obtained proton nuclear magnetic resonance spectrum is shown in Fig. 3, and the carbon nuclear magnetic resonance spectrum is shown in Fig. 4.

Analytical data of polyether with 3 trans-fused cyclic ethers:

¹ H NMR (400MHz, CDCl ₃ ) δ 3.76 (s, 1H), 3.63-3.48 (m, 4H), 2.11-1.90 (m, 2H), 1.85-1.78 (m, 3H), 1.66-1.57 (m , 4H), 1.54-1.41(m, 3H), 1.25(s, 3H), 1.24(s, 3H), 1.23(s, 3H), 1.09(s, 3H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 78.9, 78.1, 77.7, 77.1, 76.6, 70.4, 60.7, 40.3, 35.8, 28.91, 28.87, 27.5, 26.3, 25.6, 21.5, 18.6, 16.3;

HRMS (ESI): m/z C ₁₇ H ₃₀ O ₄ Na[M+Na] ⁺ calculated value 321.2036, measured value 321.2036.

Example 3:

The diastereomer mixture of tetraepoxy alcohol obtained by Shi asymmetric epoxidation (73.6mg, 0.2mmol, according to the proton nuclear magnetic spectrum analysis, the content of the tetraepoxy alcohol substrate which is all (R, R) is 75 %, ie 0.15mmol) was dissolved in perfluoro-tert-butanol (2mL), then 1-ethyl-3-methylimidazole tetrafluoroborate (40mg, 0.2mmol) was added to it, and the reaction was stirred at 40°C 15 hours. After the reaction was completed, water (5mL) was added to quench the reaction. The reaction mixture was extracted three times with dichloromethane, 10mL each time. The organic phases from the three extractions were combined. The organic phase was washed once with water (10mL) and then with brine (10mL) once. , And then dried with anhydrous magnesium sulfate, filtered and concentrated, using 35-50% ethyl acetate/petroleum ether as the eluent for silica gel column chromatography, the white solid (22.1mg, yield 40%) is obtained 4-ring trans-fused polycyclic ether. After ¹ H NMR, ¹³ C NMR and mass spectrometry analysis, the obtained proton nuclear magnetic resonance spectrum is shown in FIG. 5, the carbon nuclear magnetic resonance spectrum is shown in FIG. 6, and the high-resolution mass spectrum spectrum is shown in FIG. 7.

Analytical data of polyether with 4 trans-fused cyclic ethers:

¹ H NMR (400MHz, CDCl ₃ ) δ 3.81 (t, J = 8.4 Hz, 1H), 3.75 (d, J = 5.9 Hz, 1H), 3.65 (dd, J = 11.7 Hz, 2.2 Hz, 2H), 3.61-3.56(m, 1H), 3.29(dd, J=11.7Hz, 3.9Hz, 1H), 2.02-1.93(m, 2H), 1.88-1.83(m, 2H), 1.82-1.80(m, 1H) , 1.79-1.75(m, 2H), 1.70-1.66(m, 2H), 1.65-1.62(m, 2H), 1.52-1.46(m, 4H), 1.30(s, 3H), 1.24(s, 3H) , 1.23(s, 6H), 1.09(s, 3H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 79.1, 78.5, 77.7, 76.6, 76.4, 73.4, 72.8, 68.5, 59.8, 42.6, 39.4, 35.8, 29.2, 28.9, 26.0, 25.6, 24.4, 21.4, 20.3, 16.1 , 14.6;

HRMS (ESI) m/z C ₂₁ H ₃₆ O ₅ Na[M+Na] ⁺ calculated value 391.2455, measured value 391.2460.

Example 4:

The diastereomeric mixture of tetraepoxy alcohol containing cis-disubstituted olefins obtained by Shi asymmetric epoxidation (78.9 mg, 0.2 mmol, according to the analysis of hydrogen nuclear magnetic spectrum, all of which are (R, R) tetraepoxy The content of the alcohol substrate is 75%, that is, 0.15mmol) is dissolved in perfluoro-tert-butanol (2mL), and then 1-ethyl-3-methylimidazole tetrafluoroborate (40mg, 0.2mmol) is added to it , The reaction was stirred at 40°C for 15 hours. After the reaction was completed, water (5mL) was added to quench the reaction. The reaction mixture was extracted three times with dichloromethane, 10mL each time. The organic phases from the three extractions were combined. The organic phase was washed once with water (10mL) and then with brine (10mL) once. , And then dried with anhydrous magnesium sulfate, filtered and concentrated, using 35-50% ethyl acetate/petroleum ether as the eluent for silica gel column chromatography, separated to obtain a white solid (11.2mg, yield 19%) is The 4-ring trans-fused polycyclic ether of eight-membered cyclic ether. After ¹ H NMR, ¹³ C NMR and mass spectrometry analysis, the obtained proton nuclear magnetic resonance spectrum is shown in FIG. 8, the carbon nuclear magnetic resonance spectrum is shown in FIG. 9, and the high-resolution mass spectrum spectrum is shown in FIG. 10.

Analytical data of a polyether containing an eight-membered ring and having 4 trans-fused cyclic ethers:

¹ H NMR (400MHz, CDCl ₃ ) δ 5.65-5.58 (m, 1H), 5.40-5.37 (m, 1H), 4.40-4.35 (m, 1H), 4.22-4.17 (m, 1H), 3.84 (t , J=8.0Hz, 1H), 3.76-3.72(m, 2H), 3.62(dd, J=11.5Hz, 2.5Hz, 1H), 2.15(t, J=12.1Hz, 1H), 2.01-1.93(m , 2H), 1.89-1.79(m, 4H), 1.64-1.58(m, 5H), 1.51-1.42(m, 3H), 1.32(s, 3H), 1.25(s, 9H), 1.09(s, 3H) );

¹³ C NMR (100MHz, CDCl ₃ ) δ 131.1, 125.9, 79.2, 77.7, 77.4, 77.2, 76.5, 69.2, 68.5, 63.0, 39.4, 37.0, 35.8, 30.0, 29.2, 28.9, 25.6, 21.8, 21.4, 21.0 , 19.6, 16.2;

HRMS (ESI) m/z C ₂₃ H ₃₈ O ₅ Na[M+Na] ⁺ calculated value 417.2611, measured value 417.2615.

Example 5:

The diastereomer mixture of pentaepoxy alcohol obtained by Shi asymmetric epoxidation (90.5mg, 0.2mmol, according to the proton nuclear magnetic spectrum analysis, the content of all (R, R) pentaepoxy alcohol substrate is 71 %, that is, 0.142mmol) was dissolved in perfluoro-tert-butanol (2mL), then 1-ethyl-3-methylimidazole tetrafluoroborate (40mg, 0.2mmol) was added to it, and the reaction was stirred at 40°C. 15 hours. After the reaction was completed, water (5mL) was added to quench the reaction. The reaction mixture was extracted three times with dichloromethane, 10mL each time. The organic phases from the three extractions were combined. The organic phase was washed once with water (10mL) and then with brine (10mL) once. , And then dried with anhydrous magnesium sulfate, filtered and concentrated, using 35-50% ethyl acetate/petroleum ether as the eluent for silica gel column chromatography, the white solid (10.9mg, yield 17%) is obtained. 5-ring trans-fused polycyclic ether. After ¹ H NMR, ¹³ C NMR and mass spectrometry analysis, the obtained proton nuclear magnetic resonance spectrum is shown in FIG. 11, the carbon nuclear magnetic resonance spectrum is shown in FIG. 12, and the high-resolution mass spectrum is shown in FIG. 13.

Analytical data of polyether with trans-fused 7/7/6/7/6 pentacyclic ether skeleton in brevenal molecule:

¹ H NMR (400MHz, CDCl ₃ ) δ 3.75-3.71 (m, 1H), 3.70-3.66 (m, 1H), 3.62 (dd, J=11.4Hz, 2.1Hz, 1H), 3.52 (d, J= 3.8Hz, 1H), 3.49(d, J=3.4Hz, 1H), 3.47(d, J=3.9Hz, 1H), 3.44-3.40(m, 1H), 2.01-1.89(m, 3H), 1.81- 1.75 (m, 5H), 1.73-1.66 (m, 3H), 1.65-1.55 (m, 6H), 1.48-1.42 (m, 2H), 1.26 (s, 3H), 1.234 (s, 3H), 1.227 ( s, 3H), 1.217 (s, 6H), 1.08 (s, 3H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 78.9, 77.7, 77.3, 77.1, 76.7, 76.5, 76.3, 74.0, 72.6, 68.3, 60.1, 43.6, 39.2, 39.0, 35.8, 29.2, 28.9, 27.4, 26.1, 25.73 , 25.65, 21.3, 19.8, 17.0, 16.2, 15.9;

HRMS (ESI) m/z C ₂₆ H ₄₄ O ₆ Na[M+Na] ⁺ Calculated value 475.3030, actual value 475.3035.

Example 6:

The diastereomeric mixture of triepoxy alcohol obtained by Shi asymmetric epoxidation (54.0 mg, 0.2 mmol, and the content of the substrate of triepoxy alcohol which is all (R, R) according to the proton nuclear magnetic spectrum analysis is 83%, ie 0.166mmol) was dissolved in perfluoro-tert-butanol (2mL), then 1-ethyl-3-methylimidazole tetrafluoroborate (40mg, 0.2mmol) was added to it, and stirred at 40°C React for 24 hours. After the reaction was completed, water (5mL) was added to quench the reaction. The reaction mixture was extracted three times with dichloromethane, 10mL each time. The organic phases from the three extractions were combined. The organic phase was washed once with water (10mL) and then with brine (10mL) once. , And then dried with anhydrous magnesium sulfate, filtered and concentrated, using 35-50% ethyl acetate/petroleum ether as the eluent for silica gel column chromatography, the white solid (20.2mg, yield 45%) is obtained. 3-ring trans-fused polycyclic ether. After ¹ H NMR, ¹³ C NMR and mass spectrometry analysis, the obtained proton nuclear magnetic resonance spectrum is shown in FIG. 14, the carbon nuclear magnetic resonance spectrum is shown in FIG. 15, and the high-resolution mass spectrum spectrum is shown in FIG. 16.

Analytical data of polyether with 3 trans-fused cyclic ethers:

¹ H NMR (400MHz, CDCl ₃ ) δ 3.86-3.72 (m, 2H), 3.69-3.55 (m, 2H), 3.25-3.15 (m, 1H), 3.11 (dd, J = 11.9 Hz, 3.8 Hz, 1H), 1.93-1.81 (m, 5H), 1.78-1.72 (m, 1H), 1.71-1.62 (m, 3H), 1.56-1.50 (m, 1H), 1.43 (t, J=11.6Hz, 1H) , 1.26(s, 3H), 1.20(s, 3H), 1.11(s, 3H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 82.5, 79.7, 77.7, 75.8, 72.6, 70.1, 59.8, 46.4, 28.7, 25.85, 25.82, 24.7, 24.3, 21.6, 14.9;

HRMS(ESI): m/z C ₁₅ H ₂₇ O ₄ [M+H] ⁺ calculated value 271.1909, measured value 271.1903.

Example 7:

The diastereomer mixture of triepoxy alcohol obtained by Shi asymmetric epoxidation (51.2 mg, 0.2 mmol, according to the proton nuclear magnetic spectrum analysis, the content of the substrate of triepoxy alcohol which is all (R, R) is 83%, ie 0.166mmol) was dissolved in perfluoro-tert-butanol (2mL), then 1-ethyl-3-methylimidazole tetrafluoroborate (40mg, 0.2mmol) was added to it, and stirred at 40°C React for 24 hours. After the reaction was completed, water (5mL) was added to quench the reaction. The reaction mixture was extracted three times with dichloromethane, 10mL each time. The organic phases from the three extractions were combined. The organic phase was washed once with water (10mL) and then with brine (10mL) once. , Then dried with anhydrous magnesium sulfate, filtered and concentrated, using 35-50% ethyl acetate/petroleum ether as the eluent for silica gel column chromatography, the white solid (11.5mg, yield 27%) was obtained 3-ring trans-fused polycyclic ether.

When the hydroxyl group of triepoxy alcohol is protected as a protective group sensitive to acidic conditions, the right-to-left cyclization initiated by the attack of the hydroxyl group on the epoxy will be further inhibited. Under the same reaction conditions, full endo cyclization The yield of the product will increase to 52%. The diastereomer mixture of THP-protected hydroxyl triepoxy obtained by Shi asymmetric epoxidation (68.0mg, 0.2mmol, according to the proton nuclear magnetic spectrum analysis, all of which are (R, R) triepoxy substrates The content is 83%, that is, 0.166mmol) is dissolved in perfluoro-tert-butanol (2mL), and then 1-ethyl-3-methylimidazole tetrafluoroborate (40mg, 0.2mmol) is added to it, at 40℃ The reaction was stirred for 24 hours. After the reaction was completed, water (5mL) was added to quench the reaction. The reaction mixture was extracted three times with dichloromethane, 10mL each time. The organic phases from the three extractions were combined. The organic phase was washed once with water (10mL) and then with brine (10mL) once. , And then dried with anhydrous magnesium sulfate, filtered and concentrated, using 35-50% ethyl acetate/petroleum ether as the eluent for silica gel column chromatography, separated to obtain a white solid (22.1mg, yield 52%), which is 3-ring trans-fused polycyclic ether.

The product was ^{analyzed by 1} H NMR, ¹³ C NMR and mass spectrometry. The obtained proton nuclear magnetic resonance spectrum is shown in FIG. 17, the carbon nuclear magnetic resonance spectrum is shown in FIG. 18, and the high-resolution mass spectrum spectrum is shown in FIG. 19.

Analytical data of polyether with 3 trans-fused cyclic ethers:

¹ H NMR (400MHz, CDCl ₃ ) δ3.92-3.86 (m, 1H), 3.82-3.77 (m, 1H), 3.71-3.63 (m, 1H), 3.41-3.31 (m, 1H), 3.22-3.10 (m, 1H), 3.02-2.89 (m, 2H), 2.16-2.08 (m, 1H), 2.07-2.00 (m, 1H), 1.90-1.81 (m, 4H), 1.72-1.64 (m, 3H) , 1.44-1.35(m, 2H), 1.27(s, 3H), 1.12(s, 3H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 81.0, 77.8, 76.89, 76.83, 75.8, 70.1, 67.7, 38.3, 29.3, 28.7, 25.8, 25.4, 24.7, 21.4;

HRMS(ESI)m/z C ₁₄ H ₂₅ O ₄ [M+H] ⁺ calculated value 257.1753, measured value 257.1749.

Example 8:

The diastereomer mixture of tetraepoxy alcohol obtained by Shi asymmetric epoxidation (70.8 mg, 0.2 mmol, according to the hydrogen nuclear magnetic spectrum analysis, the content of which is all (R, R) tetraepoxy alcohol substrate is 75 %, ie 0.15mmol) was dissolved in perfluoro-tert-butanol (2mL), then 1-ethyl-3-methylimidazole tetrafluoroborate (40mg, 0.2mmol) was added to it, and the reaction was stirred at 40°C 24 hours. After the reaction was completed, water (5mL) was added to quench the reaction. The reaction mixture was extracted three times with dichloromethane, 10mL each time. The organic phases from the three extractions were combined. The organic phase was washed once with water (10mL) and then with brine (10mL) once. , And then dried with anhydrous magnesium sulfate, filtered and concentrated, using 35-50% ethyl acetate/petroleum ether as the eluent for silica gel column chromatography, the white solid (11.2mg, yield 21%) was obtained. 4-ring trans-fused polycyclic ether. After ¹ H NMR, ¹³ C NMR and mass spectrometry were performed, the obtained proton nuclear magnetic resonance spectrum is shown in FIG. 20, the carbon nuclear magnetic resonance spectrum is shown in FIG. 21, and the high-resolution mass spectrum spectrum is shown in FIG. 22.

Analytical data of polyether with 4 trans-fused cyclic ethers:

¹ H NMR (400MHz, CDCl ₃ ) δ 3.90-3.87 (m, 1H), 3.75 (d, J = 5.0 Hz, 1H), 3.68 (dd, J = 11.9 Hz, 4.3 Hz, 1H), 3.61 (dd , J=11.4Hz, 2.4Hz, 1H), 3.40-3.32 (m, 1H), 3.20-3.14 (m, 1H), 2.96-2.90 (m, 1H), 2.00-1.93 (m, 3H), 1.91 1.84(m, 3H), 1.82-1.79(m, 3H), 1.70-1.64(m, 3H), 1.52-1.42(m, 3H), 1.27(s, 3H), 1.24(s, 6H), 1.09( s, 3H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 79.2, 78.4, 77.7, 77.6, 77.2, 76.5, 70.6, 69.2, 67.9, 39.5, 35.7, 34.1, 29.9, 29.0, 28.9, 25.73, 25.64, 21.5, 19.8, 16.2 ；

HRMS (ESI) m/z C ₂₀ H ₃₄ O ₅ Na[M+Na] ⁺ calculated value 377.2298, measured value 377.2302.

Example 9:

The diastereomer mixture of tetraepoxy alcohol obtained by Shi asymmetric epoxidation (68.0mg, 0.2mmol, according to the hydrogen nuclear magnetic spectrum analysis, the content of all tetraepoxy alcohol substrates of (R, R) is 75 %, ie 0.15mmol) was dissolved in perfluoro-tert-butanol (2mL), then 1-ethyl-3-methylimidazole tetrafluoroborate (40mg, 0.2mmol) was added to it, and the reaction was stirred at 40°C 20 hours. After the reaction was completed, water (5mL) was added to quench the reaction. The reaction mixture was extracted three times with dichloromethane, 10mL each time. The organic phases from the three extractions were combined. The organic phase was washed once with water (10mL) and then with brine (10mL) once. , Then dried with anhydrous magnesium sulfate, filtered and concentrated, used 35-50% ethyl acetate/petroleum ether as the eluent for silica gel column chromatography, separated to obtain a colorless oil (9.7mg, yield 19%) that is A trans-fused polycyclic ether with 4 rings.

When the hydroxyl group of tetraepoxy alcohol is protected as a protective group sensitive to acidic conditions, the right-to-left cyclization initiated by the attack of the hydroxyl group on the epoxy will be further inhibited. Under the same reaction conditions, full endo cyclization The yield of the product will increase to 32%. The diastereomer mixture of THP-protected hydroxyl tetraepoxy obtained by Shi asymmetric epoxidation (84.9mg, 0.2mmol, according to the hydrogen nuclear magnetic spectrum analysis of the content of all (R, R) tetraepoxy substrates 75%, ie 0.15mmol) was dissolved in perfluoro-tert-butanol (2mL), and then 1-ethyl-3-methylimidazole tetrafluoroborate (40mg, 0.2mmol) was added to it, at 40℃ The reaction was stirred for 20 hours. After the reaction was completed, water (5mL) was added to quench the reaction. The reaction mixture was extracted three times with dichloromethane, 10mL each time. The organic phases from the three extractions were combined. The organic phase was washed once with water (10mL) and then with brine (10mL) once. , Then dried with anhydrous magnesium sulfate, filtered and concentrated, using 35-50% ethyl acetate/petroleum ether as the eluent for silica gel column chromatography, separated to obtain a colorless oil (16.3mg, yield 32%) that is A trans-fused polycyclic ether with 4 rings.

The product was ^{analyzed by 1} H NMR, ¹³ C NMR and mass spectrometry, and the obtained proton nuclear magnetic resonance spectrum is shown in FIG. 23, the carbon nuclear magnetic resonance spectrum is shown in FIG. 24, and the high-resolution mass spectrum spectrum is shown in FIG. 25.

Analytical data of polyether with 4 trans-fused cyclic ethers:

¹ H NMR (400MHz, CDCl ₃ ) δ 3.90-3.81 (m, 3H), 3.78-3.75 (m, 1H), 3.74-3.68 (m, 2H), 3.67-3.62 (m, 1H), 3.12-3.01 (m, 1H), 2.50-2.39 (m, 1H), 1.99-1.94 (m, 1H), 1.90-1.85 (m, 3H), 1.84-1.79 (m, 5H), 1.78-1.70 (m, 3H) , 1.65-1.61 (m, 1H), 1.38-1.31 (m, 1H), 1.26 (s, 3H), 1.12 (s, 3H), 1.10 (s, 3H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 87.5, 86.8, 85.9, 81.3, 78.5, 77.2, 76.2, 75.1, 68.4, 37.4, 32.4, 30.8, 28.9, 27.85, 27.80, 25.8, 25.2, 23.7, 21.3;

HRMS(ESI)m/z C ₁₉ H ₃₃ O ₅ [M+H] ⁺ calculated value 341.2328, measured value 341.2321.

From Examples 1-9, it can be seen that the synthesis method of the present invention can obtain a polyether with 2 trans-fused cyclic ethers at a yield of up to 55%, and obtain a polyether with 3 trans-fused cyclic ethers at a yield of up to 57%. The polyether of the cyclic ether is obtained with a yield of up to 40%, and the polyether with 4 trans-fused cyclic ethers is obtained with a yield of up to 19%. It contains an eight-membered ring and has 4 trans-fused The polyether of the cyclic ether is as high as 17% to obtain the polyether with the trans-fused 7/7/6/7/6 pentacyclic ether skeleton in the brevenal molecule. It can be seen that the method for synthesizing a polyether with a trans-fused polycyclic ether skeleton structure from a long-chain homochiral polyepoxy compound through a one-step tandem reaction provided by the present invention has raw materials that can be conveniently prepared from cheap and readily available reagents. The experimental operation is simple, the reaction conditions are mild, and the reaction is fast.

The preferred embodiments of the present invention are described above, but they are not intended to limit the present invention. Those skilled in the art can make improvements and changes to the embodiments disclosed herein without departing from the scope and spirit of the present invention.

Claims

A preparation method of a trans-fused polycyclic ether compound represented by formula (I), which comprises the following steps: in the presence of a reaction medium and a salt containing a weak coordination anion, the same hand represented by formula (II) The polyepoxy compound is prepared by a one-step cyclization reaction to obtain the trans-fused polycyclic ether compound represented by formula (I);

Among them, in the trans-fused polycyclic ether compound represented by formula (I) and the homochiral polyepoxy compound represented by formula (II):

Each R is the same or different, and is independently selected from H, C 1-3 alkyl- or halogenated C 1-3 alkyl-;

Each R 1 is the same or different, and is independently selected from H, C 1-10 alkyl-, C 1-10 alkyl-OC 1-10 alkyl-, C 6-10 aryl-C 1-10 alkyl- OC 1-10 alkyl-, halogenated C 1-10 alkyl-;

Each R 2 is the same or different, and is independently selected from H, C 1-10 alkyl-, C 1-10 alkyl-OC 1-10 alkyl-, C 6-10 aryl-C 1-10 alkyl- OC 1-10 alkyl-, halo C 1-10 alkyl-; or when R 2 is connected to a double-bonded carbon atom, then R 2 does not exist;

Each n is the same or different, and is independently selected from 1, 2, 3, or 4;

When n=2 or 3 or 4, where appropriate, the polyether compound of formula (I) and the polyepoxy compound of formula (II) optionally form a C=C double between adjacent two carbon atoms The position of the C=C double bond in the polyepoxy compound of formula (II) corresponds to the position of the C=C double bond in the polyether compound of formula (I) as the product;

In the polyether compound of formula (I) and the polyepoxy compound of formula (II),
The carbon atoms in the fragments can be optionally substituted by the following groups: H, OH, C 1-4 alkyl- or halogenated C 1-4 alkyl-;

R 3 is H or an acid-sensitive hydroxyl protecting group;

In the trans-fused polycyclic ether compound represented by formula (I),
Part represents the structure of x fragments and y fragments appearing in sequence, the number of x fragments in the molecule of formula (I) is Nx≥1, the number of y fragments is Ny≥0, 1≤Nx+Ny≤20;

In the homochiral polyepoxy compound represented by formula (II),
The part represents the structure where u fragment and v fragment appear successively, the number of u fragments in the whole formula (II) molecule is Nu≥1, the number of v fragments is Nv≥0, and 1≤Nu+Nv≤20.
The preparation method according to claim 1, wherein the structures of the trans-fused polycyclic ether compound represented by formula (I) and the polyepoxy compound represented by formula (II) are as shown in the following schemes 1-11 As described in any plan,

plan 1:

Scenario 2:

Option 3:

Option 4:

Option 5:

Option 6:

Scheme 7:

Option 8:

Scheme 9:

Scheme 10

Option 11:
The preparation method according to claim 1 or 2, wherein the acid-sensitive hydroxyl protecting group is an ether protecting group or a silyl ether protecting group; the ether protecting group is, for example, 2-tetrahydropyranyl The silyl ether protecting group is for example trimethylsilyl or triethylsilyl; the acid-sensitive hydroxyl protecting group is preferably 2-tetrahydropyranyl or trimethylsilyl, more preferably 2-tetra Hydropyranyl;

And/or, attached to the & marked carbon atom
Structure is

The a terminal is connected to the epoxy group, and the b terminal is connected to the carbon atom marked with &; others
The structure is the same or different, which are independently

The c terminal is connected to the left group, and the d terminal is connected to the right group;
Each hydrogen atom in the structure is independently optionally substituted by R 4 ; R 4 is independently OH, C 1-4 alkyl- or halogenated C 1-4 alkyl-, preferably C 1-3 alkyl-, Particularly preferred is methyl;

And/or, each R is the same or different, and is independently selected from H, C 1-3 alkyl-; more preferably H, methyl, ethyl, propyl, isopropyl; most preferably H, methyl;

And/or, each R 1 is the same or different, and is independently selected from H, C 1-6 alkyl-, C 1-6 alkyl-OC 1-6 alkyl-, halo C 1-6 alkyl-; Preferably H, C 1-3 alkyl-, C 1-3 alkyl-OC 1-3 alkyl-, halogenated C 1-3 alkyl-; more preferably H, methyl, ethyl, propyl, iso Propyl; most preferably H, methyl; or, when R 1 is connected to a double-bonded carbon atom, then R 1 does not exist;

And/or, each R 2 is the same or different, and is independently selected from H, C 1-6 alkyl-, C 1-6 alkyl-OC 1-6 alkyl-, halo C 1-6 alkyl-; Preferably H, C 1-3 alkyl-, C 1-3 alkyl-OC 1-3 alkyl-, halogenated C 1-3 alkyl-; more preferably H, methyl, ethyl, propyl, iso Propyl; most preferably H, methyl; or, when R 2 is connected to a double-bonded carbon atom, then R 2 does not exist;

And/or, 1≤Nx+Ny≤15; preferably 1≤Nx+Ny≤10; more preferably 1≤Nx+Ny≤8, such as 1, 2, 3, 4, 5, 6, 7 or 8; most preferably 1≤Nx+Ny≤4; 1≤Nu+Nv≤15; preferably 1≤Nu+Nv≤10; more preferably 1≤Nu+Nv≤8, such as 1, 2, 3, 4, 5, 6, 7 or 8; most preferably 1≤Nu+Nv≤4.
The preparation method according to any one of claims 1 to 3, wherein each n is the same or different, and is independently selected from 1, 2 or 3;

And/or, both R and R 1 attached to the carbon atom marked with * are methyl groups;

And/or, R in the u, v, x and y fragments is independently H or methyl;

And/or, attached to the & marked carbon atom
Structure is

The a terminal is connected to the epoxy group, and the b terminal is connected to the carbon atom marked with &; others
The structure is the same or different, which are independently

And/or, R 2 and R connected to the carbon atom marked with & are H, or, when a double bond is connected to the carbon atom marked with &, R 2 connected to the carbon atom marked with & does not exist;

And/or, R 2 and R connected to the carbon atom marked with # are the same and are H or methyl.
The preparation method according to any one of claims 1 to 4, wherein the structure of the trans-fused polycyclic ether compound of formula (I) and the polyepoxy compound of formula (II) is as follows As described in any scheme in IV:

Scheme I:

R, R 1 , R 2 , R 3 , n,
The definition of is as described in any one of claims 1-4;

Scheme II:

R, R 1 , R 2 , R 3 , n,
The definition of is as described in any one of claims 1-4;

Scheme III:

R, R 1 , R 2 , R 3 , n,
The definition of is as described in any one of claims 1-4;

Scheme IV:

R, R 1 , R 2 , R 3 , n,
The definition of is as described in any one of claims 1-4;

Scheme V:

R, R 1 , R 2 , R 3 , n,
The definition of is as described in any one of claims 1-4.
The preparation method according to any one of claims 1 to 5, wherein the structures of the trans-fused polycyclic ether compound represented by formula (I) and the polyepoxy compound represented by formula (II) are as follows :

R in the u, v, x and y fragments is independently H or methyl;

Connected to the & marked carbon atom
Structure is

The a terminal is connected to the epoxy group, and the b terminal is connected to the carbon atom marked with &; others
The structure is the same or different, which are independently

R 2 and R connected to the carbon atom marked with # are the same and are H or methyl;

R 2 connected to the carbon atom labeled & is H, or when a double bond is connected to the carbon atom labeled &, R 2 connected to the carbon atom labeled & does not exist.
The preparation method according to any one of claims 1-6, wherein the structures of the trans-fused polycyclic ether compound represented by formula (I) and the polyepoxy compound represented by formula (II) are as follows Defined by any group:
The preparation method according to any one of claims 1-7, wherein the reaction medium is selected from a C 1-10 alkyl alcohol substituted by one or more halogens or a mixed solvent with other solvents, The other solvent is selected from C 1-10 alkanes substituted with one or more halogens, C 1-10 ethers or cyclic ethers optionally substituted with one or more halogens, and C 1- substituted optionally by one or more halogens. 10 esters;

And/or, the anion in the salt containing a weak coordination anion is selected from fluorine-containing weak coordination anions;

And/or, the cation in the salt containing weak coordination anion is selected from quaternary ammonium ion or quaternary phosphorus ion.
The production method according to claim 8, wherein said one or more halogen substituted C 1- 10 alkyl alcohol is selected from one or more halogen substituted C 1-8 alkyl alcohol, preferably C 1-6 alkyl alcohol substituted by one or more halogens , more preferably C 1-4 alkyl alcohol substituted by one or more halogens, the halogen being selected from fluorine, chlorine, bromine, and iodine; One or more halogen-substituted C 1-10 alkyl alcohols such as trifluoromethanol, trifluoroethanol, perfluoroethanol, trifluoropropanol, hexafluoropropanol, perfluoropropanol, trifluorobutanol, hexafluorobutanol Alcohol, perfluorobutanol, trifluoropentanol, hexafluoropentanol, perfluoropentanol, trifluorohexanol, hexafluorohexanol, perfluorohexanol;

And/or, the other solvent is selected from chloroform, dichloromethane, 1,2-dichloroethane, 1,1-dichloroethane ethyl ether, tetrahydrofuran, 1,4-dioxane;

And/or, the anion of the salt containing weak coordination anion is selected from the group consisting of tetrafluoroborate anion, hexafluorophosphate anion, hexafluoroantimonate anion, trifluoromethanesulfonic acid anion, tetra[3,5-bis(trifluoro (Methyl) phenyl] borate anion, tetrakis (pentafluorophenyl) borate anion; preferably tetrafluoroborate anion, hexafluorophosphate anion; most preferably tetrafluoroborate anion;

And/or, the cation of the salt containing weak coordination anion is selected from the group consisting of tetramethylammonium ion (Me 4 N + ), tetraethylammonium ion (Et 4 N + ), tetra-n-butylammonium ion ((n -Bu) 4 N + ), tetraphenyl quaternary phosphate ion (Ph 4 P + ), 1-butyl-3-methylimidazole quaternary ammonium ion ([BMIM]), 1-ethyl-3-methylimidazole Quaternary ammonium ion ([EMIM]), 1-hexyl-3-methylimidazole quaternary ammonium ion ([HMIM]); preferably 1-butyl-3-methylimidazole quaternary ammonium ion ([BMIM]), 1-ethyl 3-methylimidazole quaternary ammonium ion ([EMIM]); more preferably 1-ethyl-3-methylimidazole quaternary ammonium ion ([EMIM]).
The preparation method according to claim 9, wherein the reaction medium is trifluoromethanol, trifluoroethanol, perfluoroethanol, trifluoropropanol, hexafluoropropanol, perfluoropropanol, trifluorobutanol , Hexafluorobutanol, perfluorobutanol, trifluoropentanol, hexafluoropentanol, perfluoropentanol, trifluorohexanol, hexafluorohexanol, perfluorohexanol; preferably 2,2,2-tri Fluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, perfluoro-tert-butanol, more preferably perfluoro-tert-butanol;

And/or, the anion of the weakly coordinated anion-containing salt is selected from: [BMIM]BF 4 , [BMIM]PF 6 , [EMIM]BF 4 , [EMIM]PF 6 , [HMIM]BF 4 or [HMIM ]PF 6 ; preferably [BMIM]BF 4 , [EMIM]BF 4 , [HMIM]BF 4 ; more preferably [EMIM]BF 4 .