CN112110951B - A class of bryozoin C-ring skeleton compounds, synthesis method and use thereof - Google Patents

Abstract

The invention discloses a class of bryozoin C-ring skeleton compounds, a synthesis method and uses thereof, and belongs to the technical field of chemical synthesis of natural products. In the present invention, an alkenone compound and an iodo hydrocarbon compound are subjected to an aqueous free radical coupling reaction to obtain a C-ring precursor compound, that is, a bryophytin C-ring skeleton compound; Epoxidation to open epoxy, oxidation, and Aldol reaction to obtain known compounds of bryozoin C-ring precursors, combined with existing technologies (such as: Luche reductive butyrylation, TABF desiliconization, DMP oxidation and Sharpless asymmetric bishydroxylation) chemical reaction, etc.) to obtain the analogs of bryostatin C compounds, which can be used as an important synthon compound library for drug screening to promote the drug development and clinical research of the Bryostatins family. The synthesis process involves high synthesis efficiency, and compared with the existing synthesis route, the operation steps are reduced, and the entire synthesis cycle is shortened.

Description

A class of bryozoin C-ring skeleton compounds, synthesis method and use thereof

technical field

The invention relates to a class of bryozoin C-ring skeleton compounds, a synthesis method and uses thereof, and belongs to the technical field of chemical synthesis of natural products.

Background technique

Bryostatins (Bryostatins, 1968) is a compound extracted from the marine bryozoans total Bryostatin, which is a class of marine macrolide compounds with anti-cancer, anti-AIDS and anti-Alzheimer's disease. and so on. Since Pettit's team identified this compound as Bryostatin 1 with the help of single crystal and spectroscopic techniques in 1982, so far, the number of members of this natural product has been increased to 21 by extraction and isolation studies, among which, Bryostatin 1 The discovery of anticancer activity started with the detection of its ability to inhibit the proliferation of murine P388 lymphocytic leukemia cells, followed by the discovery that this natural product has significant antitumor activity against a range of cancer cells in vitro and in vivo, including HL-60 Human promyelocytic leukemia cells, P388 lymphoid leukemia, B16 melanoma, and M5076 reticulocyte malignancy. In view of the above good experimental results, scientists have launched some anti-cancer clinical studies on Bryostatin 1, and Bryostatin 1 has been used alone or in combination with other chemotherapy drugs in more than 80 clinical trials.

The Bryostatin family is a class of 20-membered macrolide natural products with complex structures, polychiral centers, high oxidation states, and high functional groups. It belongs to polyketides in its biological origin. The skeleton structure includes: three different oxidation states. ABC polysubstituted tetrahydropyran ring, more sterically hindered C16-C17 E-type double bond linking BC ring, C18 geminal dimethyl (Bryostatins1-20) or chiral monomethyl (Bryostatins 21) and C13 \C17 two acid-base labile exocyclic unsaturated esters (except C9 and C19 of Bryostatin 16 and 17 are ketal structures). The 21 molecules in the Bryostatin family have subtle structural differences, such as: Bryostatin 1, 2, 4-15, 18 The structural differences of the 15 family molecules are only reflected in the acyloxy groups at C7 on the A ring and C20 on the C ring For substitution changes, common substituents include OAc, O ₂ C(CH ₂ ) ₂ Me, O ₂ C(CH) ₄ (CH ₂ ) ₂ Me, OPiv and the like. Some studies have reported that the C20 substituent in the Bryostatin family molecules extracted and isolated from the bryostatin groups of different depths and the growth of symbiotic bacteria has various changes, and Bryostatins molecules with different contents are obtained. In addition, Bryostatin 16 and 17 contain a special C19-C20 electron-rich double bond structure, and are generally considered to be biogenic molecules of the Bryostatins family: the C19-C20 electron-rich double bond in Bryostatin 17 can be converted to Bryostatin 18 through hydration; The C19-C20 double bond in Bryostatin 16 can be converted to other family molecules of Bryostatin 1-15, 19, 20 through oxidation reaction, hydration, or reaction with the oxidized C22 position.

Due to the challenging and unique structural framework of the natural product bryostatin family molecules, as well as their high biological activity in vitro and in vivo, and the extremely low yield of extraction and isolation from nature, their total synthesis is an urgent problem to be solved. Among them, the key to the total synthesis efficiency is: how to efficiently construct the three multi-substituted pyran rings of Bryostatins A, B, and C, especially the construction of the high oxidation state, multi-substituted A ring and C ring, which determines the specific synthesis of Bryostatin molecules. Species and synthetic route length and efficiency. At present, based on the synthesis of the three ring skeletons of A, B, and C, according to different methods of splicing ABC tricycles and constructing a 26-membered macrolide core skeleton, the main total synthesis routes include:

1. Aldol or alkylation reaction to splice AB ring, Julia olefination to connect BC ring, Yamaguchi macrolide to connect AC ring;

2. Julia olefination connects the BC ring, the alkylation reaction splices the AB ring, and the Yamaguchi macrolide connects the AC ring;

3. Au-catalyzed alkene-alkyne coupling and Michael addition to construct AB ring, Yamaguchi macrolide to construct AC ring fragment, Au-catalyzed alkene-alkyne coupling and 6-endo-dig cyclization to construct C ring;

4. Prins cyclization to construct B ring while connecting BC ring, Yamaguchi macrolide to connect AC ring.

In addition, the C-ring in Bryostatins family molecules is the pharmacodynamic recognition domain (proposed in the studies of Bryostatins analogs by Wender, Paul A group, Keck, Gary E group, Krische, Michael J group and other groups), that is, whether it is In the research of total synthesis of Bryostatins family molecules, or the synthesis of Bryostatins family analog molecules, the efficient synthesis of C ring in Bryostatins family is very important. At present, the C ring synthesis route includes the following main difficulties:

Ⅰ. Construction of C16-C17 E-double bonds: Julia-Lythgoe olefination and HWE olefination are commonly used;

Ⅱ. Synthesis of C20 and C23 chiral hydroxyl groups: commonly used C20 hydroxyl Luche reduction, C23 hydroxyl Aldol reaction;

Ⅲ. Construction of α, β-unsaturated esters outside the pyran ring: Aldol reaction is commonly used, and alkenyl silicon iodine is inserted into carbonyl.

SUMMARY OF THE INVENTION

Based on the current research status, the inventor proposed a new synthetic route of the C-ring skeleton molecule in bryophytin, and obtained a class of bryophytin C-ring skeleton compounds, and then based on a brand-new synthetic process route, a series of grasses were obtained. Bryostatin C ring precursors are known compounds, and finally combined with existing mature technologies, such as: Luche reduction butyrylation, TABF desiliconization, DMP oxidation and Sharpless asymmetric bishydroxylation, etc. (“Total Synthesis of Bryostatin 8 Using anOrganosilane-Based Strategy, 2018” (Complete synthesis of Bryostatin 8 based on an organosilane-based strategy)), to obtain the bryostatin C-ring compound or its analogs as an important synthon compound library for drug screening, effectively promoting the drug development of the Bryostatins family and clinical research.

In order to achieve the above technical purpose, the following technical solutions are proposed:

This technical solution proposes a class of bryophytin C-ring skeleton compounds, which are key intermediates for the preparation of pharmaceutical compositions comprising bryophytin or its analogs, and are represented by the following general structural formula (I):

(I)

In the general structural formula (I), R ₁ represents a group that is a straight-chain alkyl group, a cyclic alkyl group, an alkenyl group, an alkynyl group, a hydroxyl group, an ether, an ester group, a cyano group, a halogen, an amino group, an aryl group or a hetero group. Atom-substituted alkyl;

R ₂ represents a group that is a straight-chain alkyl group, a cyclic alkyl group, an alkenyl group, an alkynyl group, a hydroxyl group, an ether, an ester group, a cyano group, a halogen, an amino group, an aryl group, or an alkyl group substituted by each heteroatom;

R ₃ represents a group that is a straight-chain alkyl group, a cyclic alkyl group, an alkenyl group, an alkynyl group, an ether, a halogen, an aryl group or an alkyl group substituted by each heteroatom.

Further, the bryozoin C-ring skeleton compound is the transformation of the E-form double bond at the C25-26 position, including the following structural formula:

。

.

Further, the bryophytin C-ring skeleton compound is the transformation of the side chain at the geminal dimethyl α position and the C17 position, including the following structural formula:

。

.

Further, the bryozoin C-ring skeleton compound is the transformation of the symmetrical geminal dimethyl at the C18 position, including the following structural formula:

。

.

Further, the bryozoin C-ring skeleton compound is the transformation at the C25-26 position, the C17 position side chain and the C18 position, including the following structural formula:

This technical solution proposes a method for synthesizing a class of bryophytin C-ring skeleton compounds, which comprises performing an aqueous free radical coupling reaction with ketene compounds and iodo-hydrocarbon compounds to obtain a bryophytin C-ring skeleton compound, namely Brassin C ring precursor compound; wherein, the ketene compound is represented by the following general formula (II), and the iodo hydrocarbon compound is represented by the following general formula (III):

(II) (III).

Further, the synthetic method of the bryozoin C-ring skeleton compound comprises the following specific steps:

The ketene compounds, iodo hydrocarbon compounds, zinc powder, cuprous iodide, anhydrous ethanol and TPGS aqueous solution were added to the reaction device respectively, and the reaction was stirred at 0-40 °C for 8-24 hours; Add the same amount of zinc powder, cuprous iodide, anhydrous ethanol and TPGS aqueous solution (for example: TPGS-750-M, purchased directly), stir and react at 0-40 ℃ for 8-24 hours, then add to the reaction device Add water to quench; then, extract with ethyl acetate, combine the organic phases, dry over anhydrous sodium sulfate, and concentrate under reduced pressure; and then purify with silica gel column to obtain bryophytin C-ring skeleton compound as pale yellow liquid. The reaction process is as follows:

(II) (III) (I)

Further, the zinc powder can also be replaced with zinc particles, but zinc powder is preferred, which can effectively ensure the product yield.

Further, the purity of the cuprous iodide is >90%.

Further, before feeding into the reaction device, the ketene compound and the iodo hydrocarbon compound are prepared into the corresponding ethanol solution with the dehydrated ethanol used, so as to promote the sufficient contact of the materials in the reaction process, and avoid the influence of excessive local concentration. Reaction quality and efficiency; wherein, in the preparation process of the corresponding ethanol solutions of ketene compounds and iodo hydrocarbon compounds, it is sufficient to ensure that the total amount of ethanol entering the reaction device is constant.

Further, in the TPGS aqueous solution, the mass fraction of TPGS is 1-5%, preferably 2%.

Further, the stirring speed is 400-2400 r/min, which effectively ensures more sufficient contact between various substances and improves the quality and efficiency of the reaction.

Further, the material ratio of the ketene compound and the iodo hydrocarbon compound is 2:1-1:6, and the material ratio of the ketene compound and the zinc is 1:1-1:8 , and the ratio of ketene compound to cuprous iodide substance is 1:0.2-1:3.6.

Further, the material ratio of the ketene compound, the iodo hydrocarbon compound, the zinc and the copper iodide is 1.0:3.0:5.0:1.2.

Further, the preparation method of described ketene compound, comprises the steps:

X1: Under argon protection and -78 ℃ conditions (to create a low-temperature anhydrous and oxygen-free reaction environment), add diisopropylamide lithium-n-hexane solution to the reaction device equipped with tetrahydrofuran, and then add isobutyric acid Slowly added, stirred and reacted at -78 °C for 1.5 h, then heated to -40 °C for 1 h; at -40 °C, added 3-bromopropene in tetrahydrofuran solution, and then warmed to room temperature for 10 h; then, Quench by adding ammonium chloride aqueous solution, extract with ethyl acetate, combine the organic phases, dry with anhydrous sodium sulfate, and concentrate under reduced pressure; and then purify with silica gel column to obtain the intermediate product X1 as pale yellow liquid;

X2: add the obtained intermediate product X1 to the reaction device equipped with carbon tetrachloride, then add N-bromosuccinimide and dibenzoyl peroxide, evacuate, pass argon into the reaction device at 105°C The reaction was stirred for 1 h; then, cooled to room temperature, allowed to stand, quenched by adding water, extracted with dichloromethane, combined with the organic phases, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and spin-dried to obtain an intermediate product as a colorless liquid x2;

X3: at 0°C, add 2,6-di-tert-butyl-4-methylpyridine into dichloromethane, cool for 5 min, and then add silver trifluoromethanesulfonate and TBDSOH in sequence; at 0°C After stirring the reaction for 5 min, slowly add the dichloromethane solution of the intermediate product X2, and continue to stir the reaction at 0 °C for 45 min; then, add water to quench, extract with dichloromethane, combine the organic phases with anhydrous sulfuric acid dried over sodium, concentrated under reduced pressure; purified by silica gel column chromatography to obtain intermediate product X3 as a colorless liquid;

X4: Under the protection of argon, the intermediate product X3 was added to the reaction device equipped with tetrahydrofuran, cooled at -20 ° C for 10 min, then N,O-dimethylhydroxylamine hydrochloride was added, and after the reaction was stirred for 10 min, slowly The n-hexane solution of i-PrMgCl was added, the dripping rate was controlled for 45 min, and the temperature was raised to -10 °C for 1 h; then, at room temperature, quenched by adding water, extracted with ethyl acetate, combined with the organic phases Dry over sodium sulfate and concentrated under reduced pressure; then purify with silica gel column to obtain the intermediate product X4 as pale yellow liquid;

X5: Under the protection of argon and at 0 °C, the intermediate product X4 was added to tetrahydrofuran, after cooling for 10 min, the n-hexane solution of vinylmagnesium bromide was slowly added, and the reaction was carried out at 0 °C for 3 h; Then, it was quenched by adding ammonium chloride aqueous solution, extracted with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure; and then purified by silica gel column chromatography to obtain the product X5 (that is, alkene) as a pale yellow liquid. ketone products).

Further, in the diisopropylamide lithium-n-hexane solution, the mass fraction of diisopropylamide lithium is 10.7%.

Further, in step X1, the material ratio of the lithium diisopropylamide-n-hexane solution, the isobutyric acid and the tetrahydrofuran solution of 3-bromopropene is 1.1:1.0:1.0.

Further, in step X2, the material ratio of the intermediate product X1, N-bromosuccinimide and dibenzoyl peroxide is 1:1.3:0.02.

Further, in step X3, the amounts of the 2,6-di-tert-butyl-4-methylpyridine, N-bromosuccinimide silver trifluoromethanesulfonate, TBDSOH and the intermediate product X2 The ratio is 1.5:1.2:1.0:1.0.

Further, in the n-hexane solution of i-PrMgCl, the mass fraction of i-PrMgCl is 1.1%.

Further, in step X4, the material ratio of the n-hexane solution of the intermediate product X3, N,O-dimethylhydroxylamine hydrochloride and i-PrMgCl is 1.0:5.0:10.2.

Further, in the n-hexane solution of vinylmagnesium bromide, the mass fraction of vinylmagnesium bromide is 1.4%.

Further, in step X5, the material ratio of the intermediate product X4 and the n-hexane solution of vinylmagnesium bromide is 1.0:5.0.

Further, the preparation method of described iodo hydrocarbon compound, comprises the steps:

Y1: Under argon protection and -78°C, add propyne-tetrahydrofuran solution to ethylene glycol dimethyl ether, cool for 5 min, slowly add n-butyllithium-tetrahydrofuran solution, stir and react for 10 min, then heat up to -40 °C, react for 30 min, then drop to -78 °C; then, add (R)-benzyloxymethyloxirane-tetrahydrofuran solution, add boron trifluoride-diethyl ether solution for 5 min, and react for 15 min Then, the temperature was raised to 0 °C, and the reaction was carried out at 0 °C for 1 h; then, the reaction was carried out at room temperature for 10 min, quenched by adding ammonium chloride aqueous solution, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous sodium sulfate, and then reduced Concentrate under pressure; Purify with silica gel column to obtain intermediate product Y1 as pale yellow liquid;

Y2: at 10°C, the intermediate product Y1 was added to the ultra-dry solvent dimethyl ether, then lithium aluminum hydride powder was added, then heated to 100°C, and refluxed for 8 h at 100°C; then, cooled to 15 ℃, add ice cubes to quench; slowly add 2 mol/L hydrochloric acid under stirring until no more bubbles emerge, extract with ethyl acetate, combine the organic phases, dry with anhydrous sodium sulfate, and concentrate under reduced pressure; Purified by silica gel column chromatography to obtain intermediate product Y2 as a colorless liquid;

Y3: Add lithium particles and naphthalene into tetrahydrofuran at room temperature, and react under stirring for 45 min to form a dark green lithium naphthalene solution; at -20 ℃, add the intermediate product Y2 to the dark green lithium naphthalene solution , the reaction was stirred for 30 min; then, at room temperature, an aqueous ammonium chloride solution was slowly added to quench, extracted with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure; Intermediate product C is obtained as a colorless liquid;

Y4: at room temperature and under the protection of argon, the intermediate product Y3 was added to dichloromethane, then triethylamine and Bu ₂ SnO were added in sequence, and after stirring for 5 min, p-toluenesulfonyl chloride was added, and the reaction was stirred for 2 h; Then, add water to quench, extract with dichloromethane, combine the organic phases, dry with anhydrous sodium sulfate, and concentrate under reduced pressure to obtain the intermediate product Y4 which is a pale yellow liquid crude product;

Y5: at room temperature, the obtained intermediate product Y4 and sodium iodide were added to acetone, and the reaction was refluxed under argon for 12 h; then, sodium thiosulfate was added to quench, extracted with ethyl acetate, and the organic phases were combined with Dry over sodium sulfate and concentrate under reduced pressure; and then purify with silica gel column to obtain product Y5 (i.e., iodo hydrocarbon compound) as pale yellow liquid.

Further, in the tetrahydrofuran solution of propyne, the mass fraction of propyne is 7.31%.

Further, in the tetrahydrofuran solution of described n-butyl lithium, the mass fraction of n-butyl lithium is 1.168%

Further, in step Y1, the material ratio of the propyne-tetrahydrofuran solution, n-butyllithium-tetrahydrofuran solution, 8-tetrahydrofuran solution and boron trifluoride-diethyl ether solution is 2.0:2.0:1.0:2.0 .

Further, in step Y2, the material ratio of the intermediate product Y1 to the lithium aluminum hydride powder is 1.0:5.4.

Further, in step Y3, the material ratio of the lithium particles, naphthalene and the intermediate product Y2 is 8.0:8.0:1.0.

Further, in step Y4, the material ratio of the intermediate product Y3, triethylamine, Bu ₂ SnO and p-toluenesulfonyl chloride is 1.0:1.0:0.02:1.0.

Further, in step Y5, the material ratio of the intermediate product Y4 to sodium iodide is 1:5.0.

Further, in chromatographic silica gel column purification, petroleum ether-ethyl acetate system is used as developing solvent.

Further, in the quenching, the ammonium chloride is a saturated aqueous ammonium chloride solution.

Further, in the quenching, the sodium thiosulfate is a saturated aqueous solution of sodium thiosulfate.

Based on the obtained Brassin C-ring skeleton compound, the technical solution also proposes a Brassin C-ring compound or an analog thereof, which is prepared from the Brassin C-ring skeleton compound.

This technical solution also proposes a preparation method of a bryophytin C-ring compound or an analog thereof, comprising: ring-closing, epoxidizing, and oxidizing the bryophytin C-ring skeleton compound under acidic conditions. Aldol reaction to obtain a class of known compounds of bryophytin C-ring precursors; then through Luche reduction butyrylation, TABF desiliconization, DMP oxidation and Sharpless asymmetric bishydroxylation to obtain bryophytin C-ring compounds or its analogs.

Further, the synthetic method of described bryozoin C-ring compound or its analog, comprises the following specific steps:

A. Add the dichloromethane solution of the bryozoin C ring skeleton compound into a high temperature reaction device, then add 4Å molecular sieve and hydrated p-toluenesulfonic acid, react at 60-100 °C for 8-24 hours, and cool down. to room temperature, filter molecular sieves, and concentrate under reduced pressure to obtain intermediate product A of the crude product;

b. Sodium bicarbonate, methanol and MMPP·6H ₂ O were added to the obtained intermediate product A, and the reaction was carried out at -15-0 °C for 2-4 h; then, quenched by adding water, extracted with ethyl acetate, and concentrated under reduced pressure to obtain: Crude intermediate product B;

c. The obtained intermediate product B and 4Å molecular sieve were added to the dichloromethane solution, then TPAP and NMO were added, and the reaction was carried out at room temperature for 0.5-3 h; then, quenched by adding water, extracted with dichloromethane, and concentrated under reduced pressure; Silica gel column purification to obtain intermediate product C as pale yellow crude product;

D. The obtained intermediate product C was added to tetrahydrofuran to dissolve, then, potassium carbonate, methyl glyoxylate and methanol were added to the dissolved solution, and the reaction was carried out at room temperature for 0.5-3 h; quenched by adding water, extracted with ethyl acetate, and concentrated under reduced pressure ; Purify again with chromatographic silica gel column to obtain the known compound of bryozoin C-ring precursor as pale yellow crude product;

E. The obtained bryophytin C-ring precursor known compound is subjected to Luche reduction butyrylation, TABF desiliconization, DMP oxidation and Sharpless asymmetric bishydroxylation to obtain bryophytin C-ring compound or an analog thereof.

Further, in the dichloromethane solution of the bryozoin C-ring skeleton compound of step A, the concentration of the bryophytin C-ring skeleton compound is 0.1-0.5 mol/L.

Further, in step A, the amount ratio of the bryozoin C ring skeleton compound and the substance of hydrated p-toluenesulfonic acid is 1.0: 0.01-0.2, preferably 1.0: 0.1.

Further, in step B, the material ratio of the sodium bicarbonate to MMPP·6H ₂ O is 2.0:0.5.

Further, in step C, after adding the obtained intermediate product B and 4Å molecular sieve into the dichloromethane solution, the concentration of the intermediate product B is 0.1-1.0 mol/L.

Further, in step C, the material ratio of TPAP and NMO is 0.1:3.0.

Further, in step D, after adding the obtained intermediate product C into tetrahydrofuran to dissolve, the concentration of the intermediate product C is 0.1-1.0 mol/L.

Further, in step D, the material ratio of the potassium carbonate to methyl glyoxylate is 5.5:2.0.

Based on the obtained bryozoin C-ring compound analogs, this technical solution also proposes a class of bryotaxin C-ring compound analogs as raw materials, using existing mature technologies (such as: " Total Synthesis of Bryostatin 8 Using an Organosilane-Based Strategy, 2018” (Complete synthesis of Bryostatin 8 using an Organosilane-Based Strategy, 2018)).

The technical solution also proposes the use of a class of bryophytin C-ring skeleton compounds, including using the brynzepin C-ring skeleton compounds for preparing the brynzepin C-ring compounds or analogs thereof, and using the bryophytin C-ring skeleton compounds to prepare The cyclic compound is used for the preparation of brynzepin, and the obtained brynoxin C-ring compound analog is used for the preparation of brynoxin analog; finally, it is used for the preparation of a product containing brynzepin or the analog thereof.

The technical solution also proposes the use of a bryozoin C-ring compound analog, including the use of a product containing the bryozoin analog.

Further, the product is used for the treatment of anti-cancer, anti-AIDS and anti-Alzheimer's disease.

The technical solution also proposes a bryozoin C-ring skeleton compound or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutical composition comprising a pharmaceutically acceptable carrier, diluent and excipient.

The technical solution also proposes a pharmaceutical composition comprising a bryozoin C-ring compound analog or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutically acceptable carrier, diluent and excipient.

The technical solution also proposes a pharmaceutical composition comprising a brynkinesin analog or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutically acceptable carrier, diluent and excipient.

In this technical solution, "rapid addition" specifically refers to: under the permission of the operating conditions, the addition method that avoids the oxidation of the reducing substances for a long time and has a bad influence on the subsequent operations and results, is a method in the field of chemical technology. normal operation.

In this technical solution, "slow addition" refers to dropwise addition, and the dropwise addition is completed within 45min-2h according to the dosage of the reagent.

In this technical solution, "quenching by adding water", "quenching by adding ammonium chloride" and "quenching by adding sodium thiosulfate" include: by adding water/ammonium chloride/sodium thiosulfate, water/ Ammonium chloride/sodium thiosulfate decomposes excess organic reagents to terminate the reaction; in addition, "quenching with ice" is to offset the heat released by the quenching reaction, so as not to boil the reaction solvent, thereby effectively controlling the reaction and avoiding impurities The generation of , to achieve the protection of the target, that is, to effectively improve the controllability and stability of the synthesis process route.

In this technical solution, "chromatographic silica gel column purification" adopts rapid column passing, so as to avoid that the generated product remains in the weakly acidic silica gel column for too long and affects the stability of the product. Among them, "fast" is the normal operation under the operating conditions.

In this technical solution, the involved TBDSOH means: tert-butyl diphenylsilanol; i-PrMgCl means: isopropyl magnesium chloride; Bu ₂ SnO means: di-tert-butyl tin oxide; TABF means: tetrabutyl fluoride Ammonium; DMP means: Dess-Martin oxidant; MMPP·6H ₂ O means: magnesium di(monoperoxyphthalic acid) hexahydrate; TPAP means: tetrapropylammonium perruthenate; NMO means: 4-methyl Morpholine-N-oxide; TPGS-750-M means:

By adopting this technical solution, the beneficial technical effects brought are as follows:

1) In the synthesis process route of the present invention, the raw materials involved are easy to obtain, the cost is low, and can meet the actual needs; a convergent synthesis method is adopted to reduce the use of protective groups and effectively ensure the target group; at the same time, no strong Carcinogenic, irritating, and toxic solvents, and the amount of solvent used is small, which can reduce waste liquid discharge and reduce environmental pressure for industrial scale-up production; in addition, the synthesis efficiency is high. Compared with the existing synthesis route, the operation steps are reduced, and the entire The cycle is greatly shortened;

2) The present invention is a diversity synthesis, and the R1, R2, and R3 groups involved in the bryozoin C-ring skeleton compound are variable, and a series of analogs can be prepared through the same synthetic route (currently, 27 kinds of analogs have been prepared. Brassin C ring skeleton compound library), in the follow-up analog design synthesis and activity research, it will provide numerous new analog structures with rich structures;

3) In the present invention, no purification process is required in steps A-D, Y4, etc., and the intermediate product can be directly used in the next process, which not only saves the time of the reaction step, but also effectively avoids the deterioration of the compound during the purification process. risk, thereby ensuring the stability of the synthesis process of the bryophytin C ring skeleton compound.

Detailed ways

By clearly and completely describing the technical solutions in the embodiments of the present invention below, it is obvious that the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

In the following examples, the equipment involved includes: Bruker AC-E400 NMR instrument, 600 MHz Agilent NMR instrument, VECTOR22 infrared spectrometer for infrared spectroscopy, Finnigan LCQDECA mass spectrometer for high-resolution mass spectrometry, 85-2 type Constant temperature magnetic stirrer (Shanghai Sile Instrument Factory), 2ZX-2 rotary vane vacuum pump (Zhejiang Huangji Qiujing Vacuum Pump Factory), AL204 1/10000 balance (Shanghai METTLER TOLEDO Instrument Co., Ltd.), SHB-III type Circulating water pump (Zhengzhou Great Wall Technology Industry and Trade Co., Ltd.), RE-2000 Rotary Evaporator (Shanghai Yarong Biochemical Instrument Factory) and HSGF 254 high-efficiency thin-layer silica gel plate (Yantai Huiyou Silica Gel Development Co., Ltd.).

The real reagents involved include:

Diethyl ether, THF and re-distillation with Na/benzophenone reflux;

DCM, MeCN, Et ₃ N were re-distilled with calcium hydride under reflux;

MeOH was re-distilled by refluxing the I ₂ /Mg system;

n-Butyllithium (2.5 M in hexane, Shangyu Hualun Chemical Co., Ltd.);

tert-butyllithium (1.3 M in pentane, Shangyu Hualun Chemical Co., Ltd.);

200-300 mesh or 300-400 silica gel for column chromatography (Qingdao Ocean Chemical Factory);

TLC color: 365 nm/254 nm UV; anisaldehyde, KMnO ₄ , phosphomolybdic acid, sulfuric acid/ethanol color;

Unless otherwise specified, other solvents and reagents are of commercially available analytical grade and used directly;

Anhydrous and oxygen-free operations are all carried out by Schlenk technology under the protection of inert gas Ar with double-row tubes. The required reaction vessels need to be dried, burned in an alcohol lamp under vacuum to remove water vapor, and cooled under argon gas.

Example 1

Using isobutyric acid and (R)-benzyloxymethyl oxirane as initial raw materials respectively, a synthetic method of a class of Brassin C-ring skeleton compounds is provided, so as to further illustrate the present invention, specifically comprising the following steps:

1. Synthesis of ketene compounds

X1. Preparation of intermediate product X1

Under argon protection and -78 ℃ conditions (to create a low-temperature, anhydrous, and oxygen-free reaction environment), to the reaction device pre-filled with 300 mL of cooled tetrahydrofuran, add diisopropylamide lithium-n-hexane solution (at 1.0 In the diisopropylamide lithium-n-hexane solution of M, there is 107 mL of diisopropylamide lithium), and then 20.0 g of isobutyric acid was slowly added, and the reaction was stirred at -78 °C for 1.5 h, and then the temperature was increased. After reacting at -40 °C for 1 h; at -40 °C, add 23.7 g of 3-bromopropene in tetrahydrofuran solution, and then warm to room temperature for 10 h; then, add 30 mL of saturated ammonium chloride aqueous solution to quench, and use Ethyl acetate (3×60 mL) was extracted, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure; and then purified with a silica gel column (petroleum ether: ethyl acetate=50:1) to obtain 22.3 g of The intermediate product X 1 of pale yellow liquid, the yield is 81%;

X2. Preparation of intermediate product X2

10 g of the obtained intermediate product X 1 (70.4 mmol) was added to the reaction apparatus equipped with 200 mL of carbon tetrachloride, and then 16 g of N-bromosuccinimide and 340 mg of dibenzoyl peroxide were added. After argon, the reaction was stirred at 105 °C for 1 h; then, cooled to room temperature, allowed to stand, quenched by adding 20 mL of water, extracted with dichloromethane (3×60 mL), and the organic phases were combined and dried over anhydrous sodium sulfate , concentrated under reduced pressure, and spin-dried to obtain 14.2 g of an intermediate product X2 as a colorless liquid, with a yield of 92%;

Wherein, for the intermediate product X 2, ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.95 (d, J = 15.6 Hz, 1H), 5.72 (dt, J ₁ = 15.6 Hz, J ₂ = 7.6 Hz, 1H), 3.95 (d, J = 7.6 Hz, 2H), 3.67(s, 3H), 1.30 (s, 6H); IR (liquid film) cm ^-1 2928w, 1739w, 1733m, 2916m,1462w, 1258w, 1221w, 1115m; HRMS (ESI-TOF, m/z) calcd for C ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 242.9991, found 242.9987;

X3. Preparation of intermediate product X3

At 0 °C, 7.0 g of 2,6-di-tert-butyl-4-methylpyridine was added to 200 mL of dichloromethane, cooled for 5 min, and then 7.0 g of silver trifluoromethanesulfonate and 5.00 g of g of TBDSOH; at 0 °C, after stirring the reaction for 5 min, slowly add 5.00 g of the obtained intermediate product X2 in dichloromethane solution, and continue to stir the reaction at 0 °C for 45 min; then, add 20 mL of water to quench, and use Extracted with dichloromethane (3×60 mL), combined the organic phases, dried over anhydrous sodium sulfate, and concentrated under reduced pressure; then purified with silica gel column (petroleum ether: ethyl acetate = 20:1) to obtain 8.10 g of Colorless liquid intermediate product X 3, the yield is 90%;

Wherein, for the intermediate product X 3, ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.68 (dd, J ₁ = 8.0 Hz, J ₂ = 1.6 Hz, 4H), 7.34-7.46 (m, 6H), 5.87 (d , J = 15.6 Hz, 1H), 5.58 (dt, J ₁ =15.6 Hz, J ₂ = 4.8 Hz, 1H), 4.21 (dd, J ₁ = 4.8 Hz, J ₂ = 1.6 Hz, 2H), 3.66 (s , 3H), 1.28 (s, 6H), 1.06 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 177.0, 135.6, 134.7, 133.8, 129.6, 127.6, 127.3, 64.4, 52.0, 43.9, 26.8 , 25.0, 19.3; IR(liquid film) cm ^-1 2931w, 2857w, 1731w, 1108m, 1140w, 699s, 740w, 608m; HRMS(ESI-TOF, m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si( M+Na) ⁺ : 419.2013, found 419.2009;

X4. Preparation of intermediate product X4

Under the protection of argon, the obtained 1.7g of intermediate product X3 was added to the reaction device equipped with 100mL of tetrahydrofuran, cooled at -20 °C for 10min, and then 2.1g of N,O-dimethylhydroxylamine hydrochloride was added, and stirring After 10 min of reaction, slowly add i-PrMgCl n-hexane solution (22.0 m Li-PrMgCl in 2.0 M i-PrMgCl n-hexane solution), control the dripping rate for 45 min, and then heat up to -10 ℃ for 1 h; then, at room temperature, add 20 mL of water to quench, extract with ethyl acetate (3 × 30 mL), combine the organic phases, dry over anhydrous sodium sulfate, and concentrate under reduced pressure; then use chromatographic silica gel Column (petroleum ether: ethyl acetate=5:1) purification, obtain 1.55g is the intermediate product X4 of pale yellow liquid, the yield is 85%;

Wherein, for the intermediate product X 4, ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.68 (dd, J ₁ = 8.0 Hz, 1.6 Hz, 4H), 7.34-7.46 (m, 6H), 5.91 (d, J = 15.6 Hz, 1H), 5.57 (dt, J ₁ =15.6 Hz, J ₂ = 4.8 Hz, 1H), 4.22 (dd, J ₁ = 4.8 Hz, J ₂ = 1.2 Hz, 2H), 3.54 (s,3H) , 3.16 (s, 3H), 1.30 (s, 6H), 1.05 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ177.1, 135.6, 135.5, 133.7, 129.6, 127.6, 126.4, 64.5, 60.6, 44.0, 33.7,26.8, 25.5, 19.2; IR (liquid film) cm ^-1 3354s, 2953w, 1606m, 1469w, 1257w,853w; HRMS (ESI-TOF, m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 448.2278, found448.2292;

X5. Preparation of intermediate product X5

Under argon protection and at 0 °C, the obtained 1.2 g of the intermediate product X 4 was added to 40 mL of tetrahydrofuran. After cooling for 10 min, the n-hexane solution of vinylmagnesium bromide (in 1.0 M vinyl bromide) was slowly added. 14.0 mL of vinylmagnesium bromide in the n-hexane solution of magnesium chloride), and reacted at 0 °C for 3 h; mL) extraction, combined the organic phases, dried over anhydrous sodium sulfate, and concentrated under reduced pressure; then purified with silica gel column (petroleum ether: ethyl acetate = 20:1) to obtain 1.05 g of product X5 (light yellow liquid) i.e. ketene compounds), the yield is 95%;

Wherein, for product X5, ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.69 (dd, J ₁ = 7.6 Hz, J ₂ =1.2 Hz, 4H), 7.35-7.47 (m, 6H), 6.68 (dd, J ₁ = 16.8 Hz, J ₂ = 10.4 Hz, 1H), 6.35 (dd, J ₁ = 17.2 Hz, J ₂ = 1.6 Hz), 5.78 (dd, J ₁ = 15.6 Hz, J ₂ = 1.2 Hz, 1H), 5.67 (dt, J ₁ = 15.6 Hz, J ₂ = 4.4 Hz, 1H), 5.62 (dd, J ₁ = 10.4 Hz, J ₂ =1.6 Hz, 1H), 4.25 (dd, J ₁ = 4.4 Hz, J ₂ = 1.2 Hz, 2H), 1.24 (s, 6H), 1.08 (s, 9H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 201.3, 135.5, 133.8, 133.6, 131.7, 129.6, 129.4, 128.0, 127.6, 64.3, 48.6, 26.8, 23.57, 19.2; IR (liquid film) cm ^-1 z) calcd for C ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 415.2064, found 415.2068;

2. Synthesis of iodohydrocarbons

Y1. Preparation of intermediate product Y1

Under argon protection and -78 °C, propyne-tetrahydrofuran solution (73.1 mL of propyne in 1.0 M propyne-tetrahydrofuran solution) was added to 600 mL of ethylene glycol dimethyl ether, cooled for 5 min , slowly add n-butyllithium-tetrahydrofuran solution (29.2 mL of n-butyllithium in 2.5M n-butyllithium-tetrahydrofuran solution), stir and react for 10 min, then heat up to -40 °C, react for 30 min, and then The temperature was lowered to -78 °C; then, (R)-benzyloxymethyl oxirane-tetrahydrofuran solution (5.6 mL, 36.7 mmol) was added, and 10.37 g of boron trifluoride-diethyl ether solution was added after 5 min, and the reaction was performed for 15 min. Then, the temperature was raised to 0 °C, and the reaction was carried out at 0 °C for 1 h; then, the reaction was carried out at room temperature for 10 min, quenched by adding 300 mL of saturated aqueous ammonium chloride solution, extracted with ethyl acetate (3 × 80 mL), and the organic After the phase, it was dried with anhydrous sodium sulfate and concentrated under reduced pressure; then it was purified with a silica gel column (petroleum ether: ethyl acetate=5:1) to obtain 7.33 g of an intermediate product Y1 which was a pale yellow liquid with a yield of 98%. ;

Wherein, for the intermediate product Y1, ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.27-7.39 (m, 5H), 4.57 (s, 2H), 3.88-3.96 (m, 1H), 3.59 (dd, J ₁ = 9.5 Hz, J ₂ = 3.9 Hz, 1H), 3.49 (dd, J ₁ = 9.5 Hz, J ₂ = 6.7 Hz, 1H), 2.54 (d, J = 3.8 Hz, 1H), 2.36-2.42 (m, 2H ),1.78 (t, J = 2.5 Hz, 3H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 137.9, 128.4, 127.7, 78.0, 74.6, 73.3, 73.0, 69.1, 23.8, 3.5; IR (liquid film) cm ^-1 3423m, 2918m, 1453w, 1114s, 698m; HRMS (ESI-TOF, m/z) calcd for C ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 227.1043, found 227.1039;

Y2. Preparation of intermediate product Y2

At 10 °C, 7.0 g of the obtained intermediate product Y1 was added to 300 mL of ultra-dry solvent dimethyl ether, and then 7.0 g of lithium aluminum hydride powder was added, then heated to 100 °C, and refluxed for 8 h at 100 °C; Then, it was cooled to 15°C and quenched by adding ice cubes; 12 mL of 2 mol/L hydrochloric acid was slowly added under stirring until no more bubbles appeared, extracted with ethyl acetate (3×80 mL), and the organic phases were combined. Dry with anhydrous sodium sulfate, concentrate under reduced pressure; Purify again with silica gel column (petroleum ether: ethyl acetate=5:1), obtain 7.0 g of intermediate product Y2 that is colorless liquid, and the yield is 99%;

Wherein, for the intermediate product Y2, ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.27-7.40 (m, 5H), 5.38-5.60 (m, 2H), 4.56 (s, 2H), 3.79-3.88 (m, 1H) ), 2.51 (dd, J ₁ = 9.5Hz, J ₁ = 3.4Hz, 1H), 2.37 (dd, J ₁ = 9.4 Hz, J ₁ = 7.5 Hz, 1H), 2.41 (br s, 1H), 2.20 ( t, J = 6.3 Hz, 2H), 1.68 (d, J = 6.1 Hz, 2H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 138.0, 128.4, 127.7, 126.5, 74.0, 73.3, 70.0, 36.7, 18.0 ; IR (liquid film) cm ^-1 3432w, 3028w, 2855m, 2916m, 1452m, 1088s, 967s, 736s; HRMS (ESI-TOF, m/z)calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 229.1199, found 229.1196;

Y3. Preparation of intermediate product Y3

At room temperature, 1.6 g of lithium particles and 28.6 g of naphthalene were added to 100 mL of tetrahydrofuran, and reacted under stirring for 45 min to form a dark green lithium-naphthalene solution; at -20 °C, 5.8 g of the intermediate product Y2 was added to the ink. In the green lithium naphthalene solution, the reaction was stirred for 30 min; then, at room temperature, 20 mL of saturated ammonium chloride aqueous solution was slowly added to quench, extracted with ethyl acetate (3 × 30 mL), and the organic phases were combined with anhydrous sodium sulfate. Dry, concentrate under reduced pressure; Purify again with chromatographic silica gel column (petroleum ether: ethyl acetate=1:1), obtain 3.0g of intermediate product Y3 that is colorless liquid, yield is 92%);

Wherein, for the intermediate product Y3, ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.34-5.60 (m, 2H), 3.65-3.73 (m, 1H), 3.63 (dd, J ₁ = 11.2 Hz, J ₂ = 3.2 Hz, 1H), 3.43 (dd, J ₁ = 11.2Hz, J ₂ = 7.2 Hz, 1H), 2.87 (br s, 2H), 2.05-2.21 (m, 2H), 1.67 (dd, J ₁ = 6.4Hz , J ₂ = 0.8 Hz, 3H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 128.9, 126.3, 71.7, 66.2, 36.7, 18.0; IR (liquid film) cm ^-1 3380s, 2921m, 1439m, 1074m, 968m , 750s; HRMS(ESI-TOF, m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 139.0730, found 139.0732;

Y4. Preparation of intermediate product Y4

Under the protection of argon at room temperature, 2.30 g of the intermediate product Y3 was added to 100 mL of dichloromethane, followed by triethylamine (19.8 mmol) and 10.0 mg of Bu ₂ SnO. After stirring for 5 min, 377.8 g of mg p-toluenesulfonyl chloride, stirred and reacted for 2 h; then, quenched by adding 20 mL of water, extracted with dichloromethane (3×20 mL), combined the organic phases, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a light yellow color Intermediate product Y4 of liquid crude product;

Y5. Preparation of intermediate product Y5

At room temperature, the obtained intermediate Y4 and 14.8 g of sodium iodide were added to 50 mL of acetone, and the reaction was refluxed under argon for 12 h; then, 20 mL of sodium thiosulfate was added to quench, and ethyl acetate (3× 30 mL) was extracted, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure; and then purified with a silica gel column (petroleum ether: ethyl acetate = 5:1) to obtain 3.8 g of product Y as a pale yellow liquid 5 (i.e. iodo hydrocarbon compound), the yield is 86%;

Wherein, for product Y 5, ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.53-5.65 (m, 1H), 5.35-5.45 (m, 1H), 3.50-3.59 (m, 1H), 3.35 (dd, J ₁ = 10.1 Hz, J ₂ = 4.0 Hz, 1H), 3.23 (dd, J ₁ = 10.1 Hz, J ₂ = 4.0 Hz, 1H), 2.20-2.34 (m, 2H), 2.11 (br s, 1H), 1.68 (dd, J ₁ = 6.3 Hz, J ₂ = 0.8 Hz, 3H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 130.0, 125.5, 70.4, 39.7, 18.0, 14.9; IR (liquid film) cm ^-1 3367w, 2918m, 2853w, 1435w, 1260w, 1011m, 967s, 750m;

3. Synthesis of Brassin C ring skeleton compounds

500.0 mg of the obtained ketenes, 861.1 mg of the obtained iodohydrocarbons, 406.4 mg of zinc powder and 294.5 mg of cuprous iodide, 1.4 mL of ethanol and 0.6 mL of TPGS aqueous solution (TPGS mass fraction of 2%, commercially available TPGS-750-M) was added to the reaction device, and reacted at 0-40 °C for 8-24 hours; then 406.4 mg of zinc powder, 294.5 mg of copper iodide, 1.4 mL of ethanol and 0.6 mL of TPGS aqueous solution were added to the reaction device. (The mass fraction of TPGS is 2%, commercially available TPGS-750-M), after reacting at 0-40 °C for 8-24 h, add 10 mL of water to the reaction device to quench; then, use ethyl acetate (5× 20 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure; and then purified with a silica gel column (petroleum ether: ethyl acetate = 5:1) to obtain 443.6 mg of bryophytes as pale yellow liquid bryocyanidin C-ring skeleton compound (numbered as bryozoin C-ring skeleton compound 0), the yield was 71%;

Among them, for Brassin C ring skeleton compound 0, ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.64-7.73 (m, 4H), 7.34-7.46 (m, 6H), 5.78 (d, J = 15.6 Hz , 1H), 5.63 (dt, J ₁ = 15.6Hz, J ₂ = 4.6 Hz, 1H), 5.33-5.59 (m, 2H), 4.23 (d, J = 4.4 Hz, 2H), 3.50-3.60(m, 1H), 2.46 (t, J =7.1 Hz, 2H), 2.15-2.25 (m, 1H), 2.00-2.12 (m, 1H), 1.90(br s, 1H), 1.68 (d, J = 6.0 Hz, 3H), 1.51-1.67 (m, 2H), 1.34-1.45 (m, 2H), 1.20 (s, 6H), 1.07 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 213.3, 135.5, 134.4,133.6, 129.6, 128.8, 128.6, 127.6, 127.0, 70.6, 64.3, 49.6, 40.6, 37.2, 36.1,26.8, 23.9, 20.0, 19,2, 18.0; IR (liquid film) cm ^-1 291m 2910w, 1641w, 1426m, 1040s, 920s, 632m; HRMS (ESI-TOF, m/z) calcdforC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ :515.2952, found 515.295.

Example 2

Based on the synthetic method of embodiment 1, the present embodiment also proposes a variety of bryozoin C-ring skeleton compounds, as follows:

Among them, the yields in the bryophytin C-ring skeleton compound numbers 0-9, 17-29, and 31-37 are the isolated yields, which are the yields obtained through silica gel purification; The yield in -16, 30, 38-40 is the NMR yield, which is the yield obtained by NMR treatment;

In addition, the bryophytin C-ring skeleton compound 0 is a precursor compound of a known natural product (bryophytin), and the bryophytin C-ring skeleton compound 1-40 is an analog of the precursor compound of the known natural product , Here, the bryophytin C-ring skeleton compounds 0-40 are collectively referred to as the bryophytin C-ring skeleton compounds.

Example 3

Based on Examples 1-2, the present embodiment also proposes the preparation methods of various Brassin C-ring skeleton compounds, which are as follows:

1) Preparation of bryophytin C-ring skeleton compound 1

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 52.3 mg of the Brassin C ring skeleton compound 1 was prepared as a pale yellow liquid, and the yield was 50%;

Wherein, for the bryozoin C-ring skeleton compound 1, [α] _D ²⁵ = -2.1° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.59-7.74 (m, 4H), 7.30-7.49 (m, 6H), 5.71-5.89 (m, 2H), 5.62 (dt, J ₁ = 15.6 Hz, J ₂ = 4.8 Hz, 1H), 5.00-5.18 (m, 2H), 4.22 (dd, J ₁ = 4.8 Hz, J ₂ = 1.6 Hz, 2H), 3.51-3.69 (m, 1H), 2.46 (t, J = 7.2 Hz, 2H), 2.22-2.33 (m, 1H), 2.08-2.20 (m , 1H), 1.51-1.72 (m, 2H), 1.34-1.46 (m, 2H), 1.20 (s, 6H), 1.06 (s, 9H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 213.3, 135.5 , 134.8,134.4, 133.6, 129.7, 128.7, 127.6, 118.0, 70.3, 64.3, 49.7, 41.8, 37.2, 36.2,26.8, 23.9, 19.9, ,19.2; IR (liquid) cm ^-1 34333 25.41w 1427w, 1108s, 1056m, 978w; HRMS (ESI-TOF, m/z) calcd for C ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 501.2795, found 501.2795;

The structural formula of the bryozoin C ring skeleton compound 1 is as follows:

2) Preparation of bryophytin C-ring skeleton compound 2

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 39.7 mg of the Brassin C ring skeleton compound 2 was prepared as a pale yellow liquid, and the yield was 42%;

Wherein, for the bryozoin C-ring skeleton compound 2, [α] _D ²⁵ = +0.35° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.62-7.72 (m, 4H), 7.33-7.47 (m, 6H), 5.76 (dt, J ₁ =15.6 Hz, J ₂ = 1.6 Hz, 1H), 5.62 (dt, J ₁ = 15.6 Hz, J ₂ = 4.8 Hz, 1H), 4.22 (dd , J ₁ = 4.8 Hz, J ₂ = 1.6 Hz, 2H), 3.49-3.59 (m, 1H), 2.45 (t, J = 7.2 Hz, 2H), 1.54-1.67 (m, 4H), 1.34-1.45 ( m, 4H), 1.16 (s, 6H), 1.06 (s, 9H), 0.91 (t, J = 6.8 Hz, 3H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 213.5, 135.5, 135.5, 134.4, 133.6,129.7, 128.7, 127.7, 127.6, 71.2, 64.3, 49.7, 39.5, 37.2, 36.9, 26.8, 23.9,19.8, 19.2, 18.8, 14.1,,; IR (liquid film) cm ^-1 2927m, 14856s 1111m, 977w, 823w, 702w; HRMS (ESI-TOF, m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ :503.2952, found 503.2950;

The structural formula of the bryozoin C ring skeleton compound 2 is as follows:

3) Preparation of bryophytin C-ring skeleton compound 3

Using the preparation method of the bryozoin C-ring skeleton compound 0 in Example 1, 32.4 mg of the bryophytin C-ring skeleton compound 3 was prepared as a pale yellow liquid, and the yield was 41%;

Wherein, for Brassin C ring skeleton compound 3, [α] _D ²⁵ = +2.1° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.62-7.71 (m, 4H), 7.33-7.46 (m, 6H), 5.76 (dt, J ₁ =15.6 Hz, J ₂ = 1.6 Hz, 1H), 5.62 (dt, J ₁ = 15.6 Hz, J ₂ = 4.8 Hz, 1H), 4.22 (dd , J ₁ = 4.8 Hz, J ₂ = 1.6 Hz, 2H), 3.55-3.67 (m, 1H), 2.45 (t, J = 6.8 Hz, 2H), 1.70-1.81 (m, 1H), 1.55-1.68 ( m, 4H), 1.31-1.39 (m, 2H), 1.19 (s, 6H), 1.06(s, 9H), 0.89 (t, J = 6.4 Hz, 6H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 213.5, 135.5, 134.4, 133.6, 129.7, 128.7, 127.7, 69.5, 64.3, 49.7, 46.6, 37.5, 37.3, 26.8, 24.6, 23.9, 23.5, 22.0, ^19.7 , 19.2 cm; , 2927m, 2856w,1707w, 1466w, 1109s, 1054w, 701s; HRMS (ESI-TOF, m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ :517.3108, found 517.3109;

The structural formula of the bryozoin C ring skeleton compound 3 is as follows:

4) Preparation of bryophytin C-ring skeleton compound 4

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 21.4 mg of the bryophytin C-ring skeleton compound 4 was prepared as a pale yellow liquid, and the yield was 30%;

Wherein, for Brassin C ring skeleton compound 4, [α] _D ²⁵ = +0.59° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.61-7.75 (m, 4H), 7.33-7.47 (m, 6H), 5.77 (dt, J ₁ =15.6 Hz, J ₂ = 1.6 Hz, 1H), 5.62 (dt, J ₁ = 15.6 Hz, J ₂ = 4.8 Hz, 1H), 4.22 (dd , J ₁ = 4.8 Hz, J ₂ = 1.6 Hz, 2H), 3.60-3.72 (m, 1H), 2.46 (t, J = 6.8 Hz, 2H), 1.55-1.74 (m, 2H), 1.31-1.53 ( ¹³ C NMR (101 MHz, CDCl ₃ ) δ213.4, 135.5, 134.4, 133.6, 129.7, 128.7, 127.6, 72.1, 64.3, 49.7, 42.2,37.3, 36.5, 26.8, 23.9, 19.9, 19.2, 7.4, (liquid film) cm ^-1 3360w, 3072w, 2854m, 2925s, 1707w, 1427w, 1109s, 1055w, 702s, 505m; HRMS(ESI-TOF, m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+ Na) ⁺ :515.2952, found 515.2957;

The structural formula of bryozoin C ring skeleton compound 4 is as follows:

5) Preparation of bryophytin C-ring skeleton compound 5

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 59.7 mg of the Brassin C ring skeleton compound 5 was prepared as a light yellow liquid, and the yield was 66%;

Wherein, for the bryozoin C-ring skeleton compound 5, [α] _D ²⁵ = +6.3° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.66 (d, J = 6.7 Hz, 4H), 7.32-7.47 (m, 6H), 5.76 (d, J = 15.7 Hz, 1H), 5.61 (dt, J ₁ = 15.6 Hz, J ₂ = 4.6 Hz, 1H), 4.22 (d, J = 3.8 Hz, 2H), 4.16 (q, J = 7.1 Hz, 2H), 3.90-4.01 (m, 1H), 3.01 (br s, 1H), 2.45(t, J = 7.1 Hz, 2H), 2.38 (dd, J ₁ = 16.5Hz, J ₂ = 9.0 Hz, 2H), 1.53-1.71 (m, 2H), 1.36-1.47 (m, 2H), 1.26 (t, J = 7.1Hz, 3H), 1.19 (s, 6H) ), 1.06 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 213.1, 173.0, 135.5, 134.4, 133.6, 129.7, 128.7, 127.6, 67.7, 64.3, 60.7, 49.7, 41.2, 37.0 26.8, 23.9, 19.8, 19.2,14.2; IR (liquid film) cm ^-1 3481w, 2928m, 2856w, 1708m, 1463w, 1427w, 1108m,739m, 701s; HRMS (ESI-TOF, m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ :547.2850, found547.2846;

The structural formula of the bryozoin C ring skeleton compound 5 is as follows:

6) Preparation of bryophytin C-ring skeleton compound 6

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 66.3 mg of the bryophytin C-ring skeleton compound 6 was prepared as a pale yellow liquid, and the yield was 45%;

Wherein, for bryophytin C-ring skeleton compound 6, [α] _D ²⁵ = -2.7° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.67 (d, J = 6.7 Hz, 4H), 7.30-7.49 (m, 6H), 5.76 (d, J = 15.6 Hz, 1H), 5.63 (dt, J ₁ = 15.6 Hz, J ₂ = 4.3 Hz, 1H), 4.24 (d, J = 3.6 Hz, 2H), 3.78-3.94 (m, 1H), 2.95 (br s, 1H), 2.36-2.60 (m, 4H), 1.56-1.74 (m, 2H), 1.46-1.55 (m, 2H), 1.20 (s, 6H), 1.07 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 213.6, 135.5, 134.1, 133.5, 129.7, 128.9, 127.6, 117.6, 67.2, 64.2, 49.6, 36.7, 35.8 , 26.8, 25.9, 23.9, 19.3, 19.2; IR (liquid film) cm ^-1 3468w, 2930w, 2856w, 2251w, 1704w, 1427m, 979w, 702s; HRMS (ESI-TOF, m/z) calcdforC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 500.2591, found 500.2587;

The structural formula of the bryozoin C ring skeleton compound 6 is as follows:

7) Preparation of bryophytin C-ring skeleton compound 7

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 56.1 mg of the bryophytin C-ring skeleton compound 7 was prepared as a pale yellow liquid, and the yield was 47%;

Wherein, for Brassin C ring skeleton compound 7, [α] _D ²⁵ = -1.9° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.62-7.73 (m, 4H), 7.32-7.48 (m, 6H), 5.78 (d, J =15.7 Hz, 1H), 5.63 (dt, J ₁ = 15.7 Hz, J ₂ = 4.6 Hz, 1H), 4.87 (s, 1H), 4.78 (s ,1H), 4.23 (d, J = 4.0 Hz, 2H), 3.63-3.76 (m, 1H), 2.47 (t, J = 7.1 Hz, 2H), 2.18 (dd, J ₁ = 13.7Hz, J ₂ = 3.2Hz, 1H), 2.03-2.13 (m, 1H), 1.74 (s, 3H), 1.56-1.72 (m, 2H), 1.37-1.46 (m, 2H), 1.20 (s, 6H), 1.07 (s , 9H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 213.3, 142.7, 135.5, 134.4, 133.6, 129.6, 128.6, 127.6, 113.4, 68.4, 64.3, 49.7, 46.0, 37.2, 3.9, 2, 2 , 20.0, 19.2; IR (liquid film)cm ^-1 3455w, 3071w, 2960w, 2929w, 2856w, 1705w, 1261w, 1106m, 701s; HRMS (ESI-TOF, m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 515.2952, found 515.2956;

The structural formula of the bryozoin C ring skeleton compound 7 is as follows:

8) Preparation of bryophytin C-ring skeleton compound 8

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 43.6 mg of the bryophytin C-ring skeleton compound 8 was prepared as a pale yellow liquid, and the yield was 46%;

Wherein, for bryophytin C-ring skeleton compound 8, [α] _D ²⁵ = +7.6° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.67 (dd, J = 7.9, 1.5 Hz, 4H), 7.34-7.43 (m, 6H), 7.30 (t, J = 7.2 Hz, 2H), 7.16-7.25 (m, 3H), 5.76 (dt, J ₁ = 15.7 Hz, J ₂ = 1.5Hz , 1H), 5.61 (dt, J ₁ = 15.7 Hz, J ₂ = 4.7 Hz, 1H), 4.22 (dd, J ₁ = 4.7 Hz, J ₂ =1.5 Hz, 2H), 3.71-3.80 (m, 1H) , 2.80 (dd, J ₁ = 13.5 Hz, J ₂ = 4.4 Hz, 1H), 2.64(dd, J ₁ = 13.5 Hz, J ₂ = 8.3 Hz, 1H), 2.45 (t, J = 7.1 Hz, 2H) , 1.66-1.74 (m, 2H), 1.41-1.50 (m, 2H), 1.19 (s, 6H), 1.06 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ213.4, 138.5, 135.5 , 134.4, 133.6, 129.7, 129.4, 128.7, 128.5, 127.7, ^126.4,72.3 , 64.3, 49.7, 44.0, 37.2, 36.2, 26.8, 23.9, 20.0, 19.2; , 1462w, 1110m, 701m, 504w; HRMS (ESI-TOF, m/z) calcdfor C ₃₄ H ₄₄ O ₃ Si (M+Na) ⁺ :551.2952, found 551.2953;

The structural formula of bryozoin C ring skeleton compound 8 is as follows:

9) Preparation of bryophytin C ring skeleton compound 9

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 31.7 mg of the bryophytin C-ring skeleton compound 9 was prepared as a pale yellow liquid, and the yield was 48%;

Among them, for the bryozoin C ring skeleton compound 9, ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.66 (d, J =6.5 Hz, 4H), 7.57 (m, 3H), 7.39 (m, 8H), 5.72 (d, J = 15.7 Hz, 1H), 5.59 (dt, J ₁ = 15.7 Hz, J ₁ = 4.7 Hz, 1H), 5.26-5.43 (m, 2H), 4.20 (d, J = 4.5 Hz, 2H ), 3.56-3.67 (m, 1H), 2.33 (t, J = 7.2 Hz, 2H), 2.08 (t, J = 5.5 Hz, 2H), 1.50-1.69 (m, 7H), 1.16 (s, 6H) , 1.05 (s, 9H), 0.36 (s, 6H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 213.1, 138.3, 135.5, 134.5, 133.7, 133.6, 129.7, 129.4, 128.5, 127.7, 127.6, 13 127.4, 72.8, 64.4, 49.6, 40.6, 37.5, 36.2, 26.8, 23.9, 20.1, 19.2, 18.0, -1.0, -1.1;

The structural formula of bryophytin C ring skeleton compound 9 is as follows:

10) Preparation of bryophytin C-ring skeleton compound 10

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, the Brassin C ring skeleton compound 10 was obtained, and the yield was 25%;

Among them, for bryocycline C ring skeleton compound 10, IR (film) cm ^-1 3417w, 3071w, 2927m, 2655w, 1989w, 1707w, 1462w, 1427w, 1109s, 1055m, 823w, 737w, 702s, 612w;

The structural formula of the bryozoin C ring skeleton compound 10 is as follows:

11) Preparation of bryophytin C-ring skeleton compound 11

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, the bryophytin C-ring skeleton compound 11 was obtained with a yield of 48%;

Wherein, the structural formula of Brassin C ring skeleton compound 11 is as follows:

12) Preparation of bryophytin C-ring skeleton compound 12

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, the bryophytin C-ring skeleton compound 12 was obtained, and the yield was 31%;

Among them, for Brassin C ring skeleton compound 12, IR (film) cm ^-1 3442w, 3071w, 2929w, 2857w, 1704w, 1461w, 1427w, 1108m, 1055w, 822w, 736m, 701s, 612w; HRMS (ESI- TOF, m/z) calcd for C ₃₂ H ₄₆ O ₃ Si (M+Na) ⁺ :529.3018, found 529.3093;

The structural formula of the bryozoin C ring skeleton compound 12 is as follows:

13) Preparation of bryozoin C ring skeleton compound 13

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, the bryophytin C-ring skeleton compound 13 was obtained, and the yield was 26%;

Among them, for bryocycline C ring skeleton compound 13, IR (film) cm ^-1 3368w, 2960m, 2931w, 2862w, 1705w, 1460w, 1363w, 1108m, 1077w, 823w, 807w, 702s, 612w; HRMS (ESI- TOF, m/z) calcd for C ₃₈ H ₅₂ O ₃ Si(M+Na) ⁺ :607.3578, found 607.3567;

The structural formula of the bryozoin C ring skeleton compound 13 is as follows:

14) Preparation of bryophytin C-ring skeleton compound 14

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, the bryophytin C-ring skeleton compound 14 was obtained, and the yield was 26%;

Among them, for bryozoin C ring skeleton compound 14, IR (film) cm ^-1 3373w, 3071w, 2920s, 2851m, 1703w, 1447w, 1427w, 1109m, 1047w, 822w, 734m, 701s, 612w; HRMS (ESI- TOF, m/z) calcd for C ₃₄ H ₅₀ O ₃ Si (M+Na) ⁺ :557.3421, found 557.3429;

The structural formula of the bryozoin C ring skeleton compound 14 is as follows:

15) Preparation of bryophytin C-ring skeleton compound 15

Using the preparation method of the bryozoin C-ring skeleton compound 0 in Example 1, the bryozoin C-ring skeleton compound 15 was obtained, and the yield was 40%;

Wherein, for bryozoin C ring skeleton compound 15, IR (film) cm ^-1 2930m, 2857w, 1706w, 1462w, 1427w, 1109m, 1057w, 917w, 822w, 702s, 612w;

The structural formula of the bryozoin C ring skeleton compound 15 is as follows:

16) Preparation of bryophytin C-ring skeleton compound 16

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, the bryophytin C-ring skeleton compound 16 was obtained, and the yield was 38%;

Among them, for bryozoin C ring skeleton compound 16, IR (film) cm ^-1 3416w, 2960w, 2928w, 2856w, 1704w, 1492m, 1461m, 1428w, 1241s, 1110s, 823w, 751m, 734m, 702s, 611w;

The structural formula of the bryozoin C ring skeleton compound 16 is as follows:

17) Preparation of bryophytin C-ring skeleton compound 17

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 61.6 mg of the bryophytin C-ring skeleton compound 17 was prepared as a pale yellow liquid, and the yield was 56%;

Wherein, for the bryozoin C-ring skeleton compound 17, [α] _D ²⁵ = +4.0° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 5.71-5.90 (m, 1H), 5.02-5.21 (m, 2H), 3.51-3.70 (m, 1H), 2.47 (t, J = 6.8 Hz, 2H), 2.28-2.38 (m, 1H), 2.22-2.31 (m, 1H), 2.08- 2.20 (m, 1H), 1.10-1.52, 1.56-1.87 (m, 14H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 214.3, 134.8, 118.1, 70.3, 50.8, 41.9, 40.3, 36.3, 28.5, 25.8 , 25.7, 19.5; IR(liquid film) cm ^-1 3456w, 2928m, 1702w, 995w; HRMS (ESI-TOF, m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ :247.1669, found 247.1673;

The structural formula of bryozoin C ring skeleton compound 17 is as follows:

18) Preparation of bryophytin C-ring skeleton compound 18

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 64.2 mg of the Brassin C ring skeleton compound 18 was prepared as a pale yellow liquid, and the yield was 65%;

Wherein, for the bryozoin C-ring skeleton compound 18, [α] _D ²⁵ = +4.1° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.56-7.68 (m, 4H), 7.31-7.49 (m, 6H), 5.71-5.95 (m, 1H), 5.05-5.18 (m, 2H), 3.64 (s, 2H), 3.56-3.65 (m, 1H), 2.57 (t, J = 6.4 Hz, 2H), 2.20-2.34 (m, 1H), 2.08-2.20 (m, 1H), 1.60-1.76 (m, 2H), 1.36-1.52 (m, 2H), 1.12 (s, 6H), 1.04 ( s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 214.8, 135.6, 134.8, 133.2, 129.7, 127.7, 118.0, 70.8, 70.3, 49.6, 31.8, 37.7, 36.3, 26.8, 21.7, 19 IR (liquid film) cm ^-1 3451w, 3072w, 2924m, 2854w, 1704w, 1462w, 1108m, 701s; HRMS (ESI-TOF, m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ :475.2639,found 475.2637;

The structural formula of the bryozoin C ring skeleton compound 18 is as follows:

19) Preparation of bryophytin C-ring skeleton compound 19

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 49.6 mg of the bryophytin C-ring skeleton compound 19 was prepared as a pale yellow liquid, and the yield was 52%;

Wherein, for the bryozoin C-ring skeleton compound 19, [α] _D ²⁵ = +5.5° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 5.71-5.91 (m, 1H), 5.06-5.19 (m, 2H), 3.55-3.68 (m, 1H), 3.56 (s, 2H), 2.70 (td, J ₁ = 6.8 Hz, J ₂ = 2.4 Hz, 2H), 2.22-2.34 (m, 1H), 2.07-2.21 (m, 1H), 1.88 (br s, 1H), 1.57-1.72 (m, 2H), 1.36-1.51 (m, 2H), 1.08 (s, 6H), 0.86 (s, 9H) ), 0.02 (s, 6H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 215.1, 134.9, 118.0, 70.3, 70.3, 49.4, 41.8, 37.8, 36.3, 25.8, 21.6, 19.3, 18.2, -5.7; IR (liquid film) cm ^-1 3441w, 2927s, 2856m, 1705w, 1468w, 1364w, 1097m,837s, 779w; HRMS (ESI-TOF, m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ :351.2326, found351.2322;

The structural formula of the bryozoin C ring skeleton compound 19 is as follows:

20) Preparation of bryophytin C-ring skeleton compound 20

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 21.6 mg of the Brassin C ring skeleton compound 20 was prepared as a pale yellow liquid, and the yield was 26%;

Wherein, for the bryophytin C-ring skeleton compound 20, [α] _D ²⁵ = -6.6° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.64 (d, J = 4.8 Hz, 4H), 7.34-7.46 (m, 6H), 5.75-5.87(m, 1H), 5.05-5.19 (m, 2H), 3.61 (t, J = 4.4 Hz, 2H), 3.54-3.63 (m, 1H) ,2.41-2.52 (m, 2H), 2.23-2.30 (m, 1H), 2.09-2.17 (m, 1H), 1.84 (t, J = 4.4 Hz, 2H), 1.53-1.63 (m, 2H), 1.33 -1.43 (m, 2H), 1.09 (s, 6H), 1.02 (s, 9H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 215.0, 135.6, 134.8, 133.6, 129.6, 127.7, 118.0, 70.4, 60.7 , 46.1, 41.9, 41.8, 36.4, 36.2, 26.8, 24.7, 19.7, 19.1; IR (liquid film)cm ^-1 3432w, 3072w, 2926m, 2855w, 1702w, 1465w, 1108w, 703w, 504w; , m/z) calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ :489.2795, found 489.2803;

The structural formula of the bryozoin C ring skeleton compound 20 is as follows:

21) Preparation of bryophytin C-ring skeleton compound 21

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 57.8 mg of the Brassin C ring skeleton compound 21 was prepared as a pale yellow liquid, and the yield was 62%;

Wherein, for the bryozoin C-ring skeleton compound 21, [α] _D ²⁵ = -6.6° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.60-7.68 (m, 4H), 7.34-7.45 (m, 6H), 5.72-5.90 (m, 1H), 5.05-5.18 (m, 2H), 3.62 (t, J = 6.4 Hz, 2H), 3.57-3.65 (m, 1H), 2.48( td, J ₁ = 6.8 Hz, J ₂ = 0.8 Hz, 2H), 2.23-2.32 (m, 1H), 2.09-2.19 (m, 1H), 1.53-1.69 (m, 4H), 1.35-1.46 (m, 4H), 1.09 (s, 6H), 1.04 (s, 9H); ¹³ C NMR (101MHz, CDCl ₃ ) δ 215.8, 135.5, 134.8, 133.9, 129.6, 127.6, 118.1, 70.4, 64.0, 47.2, 41.8, 36 , 36.3, 36.1, 27.9, 26.9, 24.3, 19.7, 19.2; IR (liquid film)cm ^-1 2929m, 2857m, 1701w, 1427w, 1092s, 1020m,799m, 702s; HRMS (ESI-TOF, m/z)calcd forC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 503.2952, found 503.2948.;

The structural formula of the bryozoin C ring skeleton compound 21 is as follows:

22) Preparation of bryophytin C-ring skeleton compound 22

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 36.8 mg of the bryophytin C-ring skeleton compound 22 was prepared as a pale yellow liquid, and the yield was 41%;

Wherein, for the bryozoin C-ring skeleton compound 22, [α] _D ²⁵ = -2.7° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.14 (t, J = 7.2 Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H), 6.87 (d, J = 8.0 Hz, 2H), 5.70-5.94 (m, 1H), 5.00-5.21 (m, 2H), 3.53-5.67 (m ,1H), 2.76 (s, 2H), 2.42 (t, J = 6.4 Hz, 2H), 2.31 (s, 3H), 2.23-2.32 (m, 1H), 2.10-2.20 (m, 1H), 1.54- 1.73 (m, 2H), 1.34-1.49 (m, 2H), 1.12 (s, 6H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 215.8, 137.7, 137.4, 134.8, 131.0, 127.8, 127.2, 127.0, 117.9, 70.3, 48.2, 45.5, 41.8, 37.8, 36.1, 24.3, 21.3, 19.5; IR (liquid film)cm ^-1 3437w, 2923m, 1698s, 1364w, 994m, 913m, 790m, 702m; m/z) calcd for C ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 311.1982, found 311.1978;

The structural formula of the bryozoin C ring skeleton compound 22 is as follows:

23) Preparation of bryophytin C-ring skeleton compound 23

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 100.3 mg of the Brassin C ring skeleton compound 23 was prepared as a pale yellow liquid, and the yield was 91%;

Wherein, for Brassin C ring skeleton compound 23, [α] _D ²⁵ = -1.3° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.55-7.68 (m, 4H), 7.31-7.47 (m, 6H), 5.71-5.90 (m, 1H), 5.04-5.18 (m, 2H), 3.67 (s, 2H), 3.55-3.65 (m, 1H), 2.38-2.54 (m, 2H) ), 2.21-2.33 (m, 1H), 2.08-2.19 (m, 1H), 1.66-1.76 (m, 2H), 1.59-1.67 (m, 2H), 1.50-1.60 (m, 2H), 1.35-1.47 (m, 2H), 1.04 (s, 9H), 0.65 (t, J = 7.6Hz, 6H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 214.7, 135.7, 134.8, 133.3, 129.7, 127.7, 118.0, 70.4, 64.1, 56.7, 41.8, 37.9, 36.4, 26.9, 23.7, 19.3, 19.3, 8.0; IR (liquidfilm) cm ^-1 2931m, 1699w, 1427w, 1261w, 1110s, 748s, 703m; HRMS (ESI-F /z) calcd for C ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 503.2952, found 503.2945;

The structural formula of the bryozoin C ring skeleton compound 23 is as follows:

24) Preparation of bryophytin C-ring skeleton compound 24

Using the preparation method of the bryozoin C-ring skeleton compound 0 in Example 1, 40.9 mg of the bryophytin C-ring skeleton compound 24 was prepared as a pale yellow liquid, and the yield was 49%;

Wherein, for the bryozoin C-ring skeleton compound 24, [α] _D ²⁵ = -1.1° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.56-7.67 (m, 4H), 7.35-7.50 (m, 6H), 5.72-5.88 (m, 1H), 5.06-5.17 (m, 2H), 3.84 (s, 2H), 3.68-3.80 (m, 4H), 5.57-3.67 (m, 1H) ), 2.45-2.63 (m, 2H), 2.23-2.32 (m, 1H), 2.07-2.18 (m, 1H), 1.63-1.79 (m, 2H), 1.36-1.51 (m, 2H), 1.04 (s , 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 207.6, 135.6, 134.6, 132.2, 130.1, 127.9, 118.2, 70.3, 64.3, 57.9, 41.9, 39.2, 35.9, 33.3, 19.8, 19. (liquid film) cm ^-1 3410w, 3072w, 2855w, 2928w, 1713w,1427w, 1110s, 702m; HRMS (ESI-TOF, m/z) calcd for C ₂₈ H ₃₈ Br ₂ O ₃ Si (M+Na) ⁺ :633.0829, found 633.0823;

The structural formula of the bryozoin C ring skeleton compound 24 is as follows:

25) Preparation of bryophytin C-ring skeleton compound 25

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, (29.7 mg of the Brassin C ring skeleton compound 25 as a light yellow liquid was prepared, and the yield was 27%;

Wherein, for the bryozoin C-ring skeleton compound 25, [α] _D ²⁵ = -2.0° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.57-7.65 (m, 4H), 7.34-7.46 (m, 6H), 5.72-5.90 (m, 1H), 5.47-5.63 (m, 2H), 4.89-5.22 (m, 6H), 3.70 (s, 2H), 3.55-3.63 (m, 1H) ), 2.40-2.50 (m, 2H), 2.29-2.42 (m, 4H), 2.20-2.29 (m, 1H), 2.07-2.18 (m, 1H), 1.54-1.70 (m, 2H), 1.34-1.46 (m, 2H), 1.06 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 213.0, 135.7, 134.8, 133.1, 133.0, 129.8, 127.7, 118.4, 118.0, 70.4, 65.5, 56.2, 41.8 , 38.5, 36.2, 35.7, 26.9, 19.3, 19.1; IR (film) cm ^-1 TOF, m/z) calcd for C ₃₂ H ₄₄ O ₃ Si (M+Na) ⁺ :527.2952, found 527.2932;

The structural formula of the bryozoin C ring skeleton compound 25 is as follows:

26) Preparation of bryozoin C ring skeleton compound 26

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 42.3 mg of the bryophytin C-ring skeleton compound 26 was prepared as a pale yellow liquid, and the yield was 46%;

Wherein, for the bryozoin C-ring skeleton compound 26, [α] _D ²⁵ = +1.4° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.58-7.70 (m, 4H), 7.33-7.49 (m, 6H), 5.72-5.89 (m, 1H), 5.02-5.20 (m, 2H), 3.85 (s, 2H), 3.55-3.66 (m, 1H), 2.70 (t, J = 7.2 Hz, 2H), 2.23-2.33 (m, 1H), 2.09-2.20 (m, 1H), 1.64-1.74 (m, 2H), 1.39-1.49 (m, 2H), 1.12-1.19 (m, 2H), 1.05 (s, 9H), 0.68-0.76 (m, 2H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 210.7, 135.6, 134.8, 133.2, 129.8, 127.7, 118.0, 70.2, 65.8, 41.8, 38.8, 36 , 32.9, 26.9, 19.5, 19.3, 15.2, 15.1; IR (liquid film) cm ^-1 3434w, 3072w, 2856w, 2927m, 1687w, 1427w, 1108s, 702s; HRMS (ESI-TOF, m/z) calcdforC ₁₉ H ₂₇ F ₃ O ₃ Si(M+Na) ⁺ : 473.2482, found 473.2487;

The structural formula of the bryozoin C ring skeleton compound 26 is as follows:

27) Preparation of bryophytin C-ring skeleton compound 27

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 39.6 mg of the bryophytin C-ring skeleton compound 27 was prepared as a pale yellow liquid, and the yield was 37%;

Wherein, for the bryozoin C-ring skeleton compound 27, [α] _D ²⁵ = +2.4° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.63 (d, J = 6.6 Hz, 4H), 7.34-7.48 (m, 6H), 5.67-5.95(m, 1H), 5.12 (d, J = 12.6 Hz, 2H), 3.88 (s, 2H), 3.55-3.66 (m, 1H), 2.50 (t, J = 6.6 Hz, 2H), 2.22-2.39 (m, 3H), 2.09-2.21 (m, 1H), 1.81-1.91 (m, 2H), 1.62-1.78 (m, 4H), 1.36-1.50 (m, 2H), 1.04 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 213.2, 135.7, 134.8, 133.2, 129.8, 127.7, 117.9, 70.4, 68.3, 55.0, 41.8, 37.2, 36.4 , 26.8, 26.3, 19.4, 19.3, 15.1; IR (film) cm ^-1 3441w, 3071w, 2930m, 2857w, 1701w, 1427w, 1108m, 1085m, 741w, 702s, 614w; HRMS (ESI-TOF, m/z) calcd for C ₂₉ H ₄₀ O ₃ Si (M+Na) ⁺ : 487.2639, found 487.2654;

The structural formula of the bryozoin C ring skeleton compound 27 is as follows:

28) Preparation of bryophytin C-ring skeleton compound 28

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 28 mg of the Brassin C ring skeleton compound 28 was prepared as a pale yellow liquid, and the yield was 50%;

Wherein, for the bryozoin C-ring skeleton compound 28, [α] _D ²⁵ = +2.0° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.60 (d, J = 6.8 Hz, 4H), 7.32-7.48 (m, 6H), 5.72-5.91(m, 1H), 5.11 (d, J = 12.6 Hz, 2H), 3.62 (s, 2H), 3.56-3.69 (m, 1H), 2.58 (td, J ₁ = 6.6 Hz, J ₂ = 1.5 Hz, 2H), 2.23-2.33 (m, 1H), 2.08-2.19 (m, 1H), 1.94-2.03 (m, 2H), 1.62-1.74 (m , 2H), 1.37-1.49 (m, 4H), 1.26-1.36 (m, 4H), 1.03(s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 213.6, 135.7, 134.8, 133.2, 129.7, ^127.7,117.9 , 70.4, 68.9, 61.7, 41.8, 38.4, 36.4, 31.8, 26.9, 25.1, 19.7, 19.3; , 734m,701s, 613w.; HRMS (ESI-TOF, m/z) calcd for C ₃₀ H ₄₂ O ₃ Si (M+Na) ⁺ :501.2795, found501.2810;

The structural formula of the bryozoin C ring skeleton compound 28 is as follows:

29) Preparation of bryozoin C ring skeleton compound 29

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 42.1 mg of the bryophytin C-ring skeleton compound 29 was prepared as a light yellow liquid, and the yield was 51%;

Wherein, for the bryozoin C-ring skeleton compound 29, [α] _D ²⁵ = -0.78° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.62 (d, J = 6.6 Hz, 4H), 7.33-7.47 (m, 6H), 5.72-5.92(m, 1H), 5.04-5.23 (m, 2H), 3.69 (s, 2H), 3.54-3.65 (m, 1H), 2.57 (t, J = 6.5Hz, 2H), 2.22-2.32 (m, 1H), 2.07-2.19 (m, 1H), 1.88-1.98 (m, 2H), 1.36-1.77(m, 12H), 1.03 (s, 9H) ; ¹³ C NMR (101 MHz, CDCl ₃ ) δ 214.2, 135.7, 134.9, 133.2, 129.7, 127.7, 117.9, 70.5, 70.1, 53.6, 41.8, 38.0, 36.4, 30.4, 26.9, 26.0,22 IR (film) cm ^-1 3433w, 3071w, 2928m, 2856m, 1701w, 1427w, 1110s, 822w, 702s, 609w; HRMS (ESI-TOF, m/z) calcd for C ₃₁ H ₄₄ O ₃ Si (M+Na ) ⁺ :515.2952, found 515.2963;

The structural formula of the bryozoin C ring skeleton compound 29 is as follows:

30) Preparation of bryophytin C-ring skeleton compound 30

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, the bryophytin C-ring skeleton compound 30 was prepared, and the yield was less than 10%;

The structural formula of the bryozoin C ring skeleton compound 30 is as follows:

31) Preparation of bryophytin C-ring skeleton compound 31

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 51.7 mg of the Brassin C ring skeleton compound 31 was prepared as a pale yellow liquid, and the yield was 48%;

Among them, for the bryozoin C-ring skeleton compound 31, [α] _D ²⁵ = +16.9° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.59-7.64 (m, 4H), 7.34-7.45 (m, 6H), 7.11 (d, J = 8.6Hz, 2H), 6.85 (d, J = 8.6 Hz, 2H), 3.79 (s, 3H), 3.68-3.76 (m, 1H), 3.63 (s, 2H), 2.75 (dd, J ₁ = 13.7 Hz, J ₂ = 4.4 Hz, 1H), 2.52-2.63 (m, 3H), 1.67-1.74(m, 2H), 1.42-1.52 (m, 2H) ), 1.11 (s, 6H), 1.03 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 214.7, 158.2, 135.6, 133.2, 130.7, 130.4, 129.7, 127.7, 114.0, 72.5, 70.8, 55 , 49.6, 43.0, 37.7, 36.2, 26.8, 21.7, 19.6, 19.3; IR (film) cm ^-1 3373w, 2961w, 2930w, 2857w, 1701w, 1612w, 1501s, 1461w, 1241m06, 1,34m 703w; HRMS (ESI-TOF, m/z) calcd for C ₃₃ H ₄₄ O ₄ Si (M+Na) ⁺ : 555.2901, found 555.2913;

The structural formula of the bryozoin C ring skeleton compound 31 is as follows:

32) Preparation of bryophytin C-ring skeleton compound 32

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 47.5 mg of the Brassin C ring skeleton compound 32 was prepared as a pale yellow liquid, and the yield was 49%;

Among them, for the bryozoin C-ring skeleton compound 32, [α] _D ²⁵ = +2.8° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.11 (d, J = 8.4 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H), 3.78 (s, 3H), 3.69-3.77 (m, 1H), 3.56 (s, 2H), 2.75 (dd, J ₁ = 13.7 Hz, J ₂ =4.5 Hz, 1H), 2.50-2.63 (m, 3H), 1.60-1.75 (m, 2H), 1.38-1.54 (m, 2H), 1.08(s, 6H), 0.86 (s, 9H), 0.02 ( s, 6H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 214.9, 158.2, 130.3, 113.9, 113.3, 72.4, 70.2, 55.2, 49.3, 43.0, 37.8, 36.2, 25.8, 25.7, 21.5, 19.5 ;IR (liquid film) cm ^-1 3436w, 2927s, 2855m, 1512m, 1464w,1246m, 1097w, 837m; HRMS (ESI-TOF, m/z) calcd for C ₂₃ H ₄₀ O ₄ Si (M+Na) ⁺ :431.2588,found 431.2590;

The structural formula of the bryozoin C ring skeleton compound 32 is as follows:

33) Preparation of bryophytin C-ring skeleton compound 33

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 50.0 mg of the Brassin C ring skeleton compound 33 was prepared as a pale yellow liquid, and the yield was 41%;

Wherein, for the bryozoin C-ring skeleton compound 33, [α] _D ²⁵ = -2.4° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.61 (d, J = 7.6 Hz, 4H), 7.34-7.48 (m, 6H), 3.80-3.90(m, 1H), 3.64 (s, 2H), 2.92 (br s, 1H), 2.53-2.69 (m, 2H), 2.47 (t, J = 5.4Hz, 2H), 1.60-1.75 (m, 2H), 1.48-1.58 (m, 2H), 1.12 (s, 6H), 1.04 (s, 9H); ¹³ CNMR (101 MHz, CDCl ₃ ) δ 215.3 , 135.6, 133.1, 129.8, 127.7, 117.6, 70.9, ^67.2,49.6 , 37.3, 36.0, 26.8, 25.9, 21.7, 19.3, 18.7; 1106m, 1088m, 806w, 736w, 701s; HRMS (ESI-TOF, m/z) calcd for C ₂₇ H ₃₇ NO ₃ Si(M+K) ⁺ :490.2174, found 490.2170;

The structural formula of the bryozoin C ring skeleton compound 33 is as follows:

34) Preparation of bryophytin C-ring skeleton compound 34

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 48.8 mg of the bryophytin C-ring skeleton compound 34 was prepared as a pale yellow liquid, and the yield was 40%;

Among them, for the bryozoin C-ring skeleton compound 34, [α]D25 = +4.7° (c = 1.0 in CHCl3); 1HNMR (400 MHz, CDCl3) δ 7.63 (d, J = 6.8 Hz, 4H), 7.37 -7.44 (m, 6H), 4.87 (s, 1H), 4.79 (s, 1H), 3.67-3.74 (m, 1H), 3.64 (s, 2H), 2.57 (t, J = 6.9 Hz, 2H), 2.17-2.22 (dd, J1 = 9.0Hz, J2 = 2.0 Hz, 1H), 2.06-2.12 (dd, J1 = 9.0Hz, J2 =6.2 Hz, 1H), 1.75 (s, 3H), 1.65-1.73 (m , 2H), 1.39-1.49 (m, 2H), 1.12 (s, 6H), 1.04 (s, 9H); 13C NMR (151 MHz, CDCl3) δ 214.7, 142.8, 135.6, 133.2,129.7, 127.7, 113.4, 70.8, 68.5, 49.6, 46.0, 37.8, 36.6, 26.8, 22.4, 21.7, 19.6, 19.3; , 613w; HRMS (ESI-TOF, m/z) calcd for C29H42O3Si (M+Na)+:489.2795, found 489.2802;

The structural formula of the bryozoin C ring skeleton compound 34 is as follows:

35) Preparation of bryophytin C-ring skeleton compound 35

Using the preparation method of the Brassin C-ring skeleton compound 0 in Example 1, the Brassin C-ring skeleton compound 35 was obtained with a yield of 41%;

Among them, for Brassin C ring skeleton compound 35, IR (film) cm-1 3444w, 3071m, 2958w, 2930w, 1731m, 1708w, 1471w, 1427w, 1106m, 1088m, 822w, 808w, 702s, 612w; HRMS( ESI-TOF, m/z) calcd for C29H42O5Si (M+Na)+:521.2694, found 521.2707;

The structural formula of the bryozoin C ring skeleton compound 35 is as follows:

36) Preparation of bryophytin C-ring skeleton compound 36

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, 23.3 mg of the bryophytin C-ring skeleton compound 36 was prepared as a pale yellow liquid, and the yield was 39%;

Wherein, for the bryozoin C-ring skeleton compound 36, [α] _D ²⁵ = -1.4° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.57-7.64 (m, 4H), 7.33-7.44 (m, 6H), 4.87 (s, 1H), 4.78 (s, 1H), 3.68-3.74 (m, 1H), 3.68 (s, 2H), 2.43-2.51 (m, 2H), 2.18 ( dd, J ₁ = 13.6 Hz, J ₂ = 3.3 Hz, 1H), 2.08 (dd, J ₁ = 13.6 Hz, J ₂ = 9.2 Hz, 1H), 1.74(s, 3H), 1.63-1.73 (m, 4H ), 1.53-1.60 (m, 2H), 1.38-1.47 (m, 2H), 1.05 (s, 9H), 0.65 (t, J = 7.4 Hz, 6H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 214.6, 142.8, 135.7,133.3, 129.7, 127.6, 113.4, 68.5, 64.1, 56.7, 46.0, 37.9, 36.6, 26.9, ^23.7,22.4 , 19.5, 19.3, 8.0; , 2930m, 2857w, 1699w, 1427w, 1107s, 1088s, 823w, 702s, 608w; HRMS (ESI-TOF, m/z) calcd forC ₃₁ H ₄₆ O ₃ Si (M+Na) ⁺ :517.3108, found 517.3117;

The structural formula of the bryozoin C ring skeleton compound 36 is as follows:

37) Preparation of bryophytin C-ring skeleton compound 37

Using the preparation method of the Brassin C ring skeleton compound 0 in Example 1, 81.2 mg of the Brassin C ring skeleton compound 37 was prepared as a pale yellow liquid, and the yield was 78%;

Wherein, for the bryozoin C-ring skeleton compound 37, [α] _D ²⁵ = +1.2° ( c = 1.0 in CHCl ₃ ); ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.53-7.70 (m, 4H), 7.31-7.48 (m, 6H), 5.53-5.63 (m, 2H), 3.68 (s, 2H), 3.50-3.61 (m, 1H), 2.37-2.56 (m, 2H), 2.13-2.27 (m, 1H) ), 1.98-2.12 (m, 1H), 1.51-1.78 (m, 9H), 1.34-1.47 (m, 2H), 1.05 (s, 9H), 0.65(t, J = 7.6 Hz, 6H); ¹³ C _Liquid film) cm ^-1 3439w, 2961w, 2929w, 2856w, 1698w,1459w, 1106m, 735m, 700.85; HRMS (ESI-TOF, m/z) calcd for C ₃₁ H ₄₆ O ₃ Si (M+Na) ⁺ :517.3108 , found 517.3114;

The structural formula of bryozoin C ring skeleton compound 37 is as follows:

38) Preparation of bryophytin C-ring skeleton compound 38

Using the preparation method of the Brassin C-ring skeleton compound 0 in Example 1, the Brassin C-ring skeleton compound 38 was obtained with a yield of 34%;

Wherein, for Brassin C ring skeleton compound 38, IR (film) cm ^-1 2930m, 1731m, 1373w, 1184m, 1110w, 704w;

The structural formula of the bryozoin C ring skeleton compound 38 is as follows:

39) Preparation of bryozoin C ring skeleton compound 39

Using the preparation method of the bryophytin C-ring skeleton compound 0 in Example 1, the bryophytin C-ring skeleton compound 39 was obtained, and the yield was 45%;

Wherein, for bryozoin C ring skeleton compound 39, IR (film) cm ^-1 2927m, 1699w, 1427w, 1109m, 824w, 703w;

The structural formula of bryozoin C ring skeleton compound 39 is as follows:

40) Preparation of bryophytin C-ring skeleton compound 40

Using the preparation method of the bryozoin C-ring skeleton compound 0 in Example 1, the bryophytin C-ring skeleton compound 40 was obtained, and the yield was 10%;

Among them, for the bryozoin C-ring skeleton compound 40, the molecular formula is: C ₂₈ H ₄₀ O ₄ Si, M+Na: 491.2588, found491.2590.

The structural formula of the bryozoin C ring skeleton compound 40 is as follows:

The polarities of the above-mentioned bryozoin C-ring skeleton compounds 10-16, 30, and 38-40 are almost the same as the by-products of iodohydrocarbon reduction, which are difficult to purify, so the yields given are NMR yields; The yields of C-ring skeleton compounds 0-9, 17-29 and 31-37 are isolated yields obtained by silica gel purification.

Example 4

Taking the bryozoin C-ring skeleton compound 0 obtained in Example 1 as a raw material, a synthetic method of a bryozoin C-ring compound is provided, to further illustrate the present invention, specifically comprising the following steps:

Z1. Preparation of Intermediate Z1

500 mg of the obtained bryozoin C-ring skeleton compound was added to a sealed tube, and then 1.20 g of 4Å molecular sieve and 19.3 mg of hydrated p-toluenesulfonic acid were added, and the reaction was carried out at 80 °C for 16 h, cooled to room temperature, and filtered through molecular sieves. , concentrated under reduced pressure to obtain the intermediate product Z1 of the crude product;

Z2. Preparation of the intermediate product Z2

After cooling the obtained intermediate product Z1 at 0 °C for 10 min, 170.7 mg of sodium bicarbonate, 10 mL of methanol and 314.7 mg of magnesium bis(monoperoxyphthalic acid) hexahydrate were added, and the reaction was carried out at 0 °C for 3 h; then , quenched by adding water, extracted with ethyl acetate (5×20 mL), and concentrated under reduced pressure to obtain the crude intermediate product Z2;

Wherein, for the intermediate product Z2, ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.64-7.73 (m, 4H), 7.33-7.45 (m, 6H), 6.12 (d, J = 15.9 Hz, 1H), 5.49- 5.59 (m, 1H), 5.31-5.50 (m, 2H), 4.21 (d, J = 4.9 Hz, 2H), 3.60-3.78 (m, 1H), 3.33-3.41 (m, 1H), 3.32 (s, 3H), 2.01-2.22 (m, 2H), 1.72-1.92 (m, 2H), 1.62 (d, J = 3.6 Hz, 3H), 1.35-1.46 (m, 2H), 1.27-1.31 (m, 2H) , 1.18 (s, 3H), 1.16 (s, 3H), 1.06 (s, 9H); ¹³ CNMR (151 MHz, CDCl ₃ ) δ 139.1, 135.6, 135.6, 134.8, 129.6, 129.5, 127.7, 127.6, 127.3, 124.8, 70.9, 69.9, 65.0, 50.8, 44.8, 38.8, 29.7, 26.8, 26.5, 24.6, 24.2, 19.2, 18.0.;

Z3. Preparation of Intermediate Z3

At room temperature, the obtained intermediate product Z2 and 100 mg of 4Å molecular sieve were added to 10 mL of CH ₂ Cl ₂ , and then 37.4 mg of TPAP and 355.0 mg of NMO were added, and the reaction was sealed at room temperature for 1 h; then, 10 mL of water was added for quenching. was quenched, extracted with dichloromethane (3×10 mL), concentrated under reduced pressure; purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain 396.2 mg of the intermediate product Z3 (light yellow crude product) (396.2 mg). The total yield of steps Z1-Z3 is 75%);

Wherein, for intermediate Z3, ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.64-7.73 (m, 4H), 7.30-7.38 (m, 6H), 6.05 (d, J = 15.9 Hz, 1H), 5.41- 5.58 (m, 3H), 4.18 (dd, J ₁ =5.0 Hz, J ₂ = 1.7 Hz, 2H), 3.74-3.85 (m, 1H), 3.27 (s, 3H), 2.43 (t, J = 7.2Hz , 2H), 2.30-2.39 (m, 1H), 2.18-2.27 (m, 1H), 1.97-2.09 (m, 1H), 1.85-1.92(m, 1H), 1.65 (d, J = 4.9 Hz, 3H ), 1.07 (s, 6H), 1.06 (s, 9H);

Z4. Preparation of Known Compounds of Brassin C-Ring Precursors

At room temperature, 300.0 mg of the obtained intermediate product Z3 was added to 20 mL of tetrahydrofuran to dissolve, and 438.0 mg of potassium carbonate, 101.9 mg of methyl glyoxylate and 20 mL of methanol were added to the dissolved solution, and the reaction was carried out at room temperature for 1 h; then , quenched by adding 5 mL of water, extracted with ethyl acetate (3 × 10 mL), concentrated under reduced pressure; purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain 289.0 mg of pale yellow crude product The product, namely the known compound of bryozoin C-ring precursor, has a yield of 85%;

Among them, for the known compound of bryozoin C ring precursor, ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.61-7.71 (m, 4H), 7.33-7.45 (m, 6H), 6.48-6.56 (m, 1H), 5.91 (d, J = 15.9 Hz, 1H), 5.46-5.64 (m, 2H), 5.42 (dt, J ₁ = 15.9 Hz, J ₂ = 4.8 Hz, 1H), 4.08-4.15 (m, 2H) ), 3.81-3.92 (m, 1H), 3.70 (s, 3H), 3.29 (s, 3H), 3.21-3.26 (m, 1H), 2.79-2.94 (m, 1H), 2.26-2.44 (m, 2H) ), 1.66 (d, J = 5.6 Hz, 3H), 1.11 (s, 3H), 1.05(s, 9H), 1.02 (s, 3H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 197.6, 166.1, 148.5, 135.5,114.9, 133.8, 133.8, 129.6, 127.7, 127.6, 125.7, 122.8, 104.4, 71.7,64.6, 51.7, 44.3, 34.6, 26.8, 22.2, 19.2, 18.0.

Z5. Preparation of Brassin C-Ring Compounds

The obtained bryostatin C-ring precursor known compounds were subjected to Luche reduction butyrylation, TABF desiliconization, DMP oxidation, and Sharpless asymmetric bishydroxylation, etc. (“Total Synthesis of Bryostatin 8 Using anOrganosilane-Based Strategy, 2018” (Complete synthesis of Bryostatin 8 based on an organosilane strategy, 2018)) to obtain the C-ring compound of bryostatin (specifically, the C-ring compound of Bryostatin 8, which can be combined with the AB ring to obtain Bryostatin 8).

Example 5

Based on Example 4, this example also proposes the preparation methods of various intermediate product Z1 analogs, as follows:

1) Preparation of intermediate product Z1-1

Using the preparation method of the intermediate product Z1 in Example 4, the corresponding crude product was obtained, which was purified by a flash silica gel column to obtain 86.3 mg of the intermediate product Z1-1 as a pale yellow liquid with a yield of 90%;

Wherein, for the intermediate product Z1-1, [α] _D ²⁵ = +7.1° ( c = 1.0 in CHCl ₃ ); ¹ H NMR (600MHz, CDCl ₃ ) δ 7.63-7.74 (m, 4H), 7.31-7.47 ( m, 6H), 5.77 (d, J = 15.6 Hz, 1H), 5.39-5.58 (m, 3H), 4.50 (t, J = 3.6 Hz, 1H), 4.22 (d, J = 5.0 Hz, 2H), 3.66-3.75 (m, 1H), 2.26-2.36 (m, 1H), 2.13-2.21 (m, 1H), 1.91-2.05 (m, 2H), 1.73-1.80 (m, 1H), 1.65 (d, J = 4.7 Hz, 3H), 1.56-1.64 (m, 1H), 1.13 (s, 6H), 1.07 (s, 9H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 159.3, 138.5, 135.6, 134.0, 129.5 ,127.5, 127.3, 127.1, 125.2, 92.7, 75.0, 65.0, 40.3, 38.1, 26.9, 26.7, 25.7,25.6, 20.1, 19.2, 18.0; IR (liquid film) cm ^-1 3071w, 5w 3049w, 28 , 1661w, 1462w, 1427w, 1107s, 1057m, 996w, 822w, 737w, 700s, 611w; HRMS(ESI-TOF, m/z) calcd for C ₃₁ H ₄₂ O ₂ Si (M+Na) ⁺ :497.2846, found 497.2840;

The structural formula of the intermediate product Z1-1 is as follows:

2) Preparation of intermediate product Z1-2

Using the preparation method of the intermediate product Z1 in Example 4, the corresponding crude product was obtained, which was purified by a flash silica gel column to obtain 31.8 mg of the intermediate product Z1-2 as a pale yellow liquid with a yield of 90%;

Wherein, for the intermediate product Z1-2, [α] _D ²⁵ = +11.3° ( c = 1.0 in CHCl ₃ ); ¹ H NMR (400MHz, CDCl ₃ ) δ 7.63-7.76 (m, 4H), 7.32-7.47 ( m, 6H), 5.76 (d, J = 15.6 Hz, 1H), 5.53 (dt, J ₁ = 15.6 Hz, J ₂ = 5.1 Hz, 1H), 4.76 (d, J = 16.8 Hz, 2H), 4.52 ( t, J = 3.7 Hz, 1H), 4.21 (d, J = 4.4 Hz, 2H), 3.83-3.93 (m, 1H), 2.35 (dd, J ₁ =14.0 Hz, J ₂ = 7.2 Hz, 1H), 2.21 (dd, J ₁ = 14.0 Hz, J ₂ = 5.5 Hz, 1H), 1.94-2.11 (m, 2H), 1.76 (s, 3H), 1.38-1.53 (m, 2H), 1.13 (s, 6H) , 1.07 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 159.5, 142.7, 138.5, 135.6, 134.1, 129.5, 127.6, 125.2, 112.3, 92.7, 73.8, 65.0, 43.3, 6.9.3 , 25.6, 22.9, 20.3, 19.2; IR(film) cm ^-1 3071w, 2927m, 2855w, 1709w, 1612w, 1461w, 1428w, 1106m, 1057m,819m, 800m, 700s, 612w; HRMS (ESI-TOF z) calcd for C ₃₁ H ₄₂ O ₂ Si (M+Na) ⁺ : 497.2846, found 497.284;

The structural formula of the intermediate product Z1-2 is as follows:

3) Preparation of intermediate product Z1-3

Using the preparation method of the intermediate product Z1 in Example 4, the corresponding crude product was obtained, which was purified by a flash silica gel column to obtain 37.6 mg of the intermediate product Z1-3 as a pale yellow liquid with a yield of 95%;

Wherein, for the intermediate product Z1-3, [α] _D ²⁵ = +10.5° ( c = 1.0 in CHCl ₃ ); ¹ H NMR (400MHz, CDCl ₃ ) δ 7.67-7.72 (m, 4H), 7.35-7.46 ( m, 6H), 5.73 (dt, J ₁ = 15.6 Hz, J ₂ = 1.2 Hz, 1H), 5.52 (dt, J ₁ = 15.6 Hz, J ₂ = 4.8 Hz, 1H), 4.59 (t, J = 3.6 Hz, 1H), 4.22 (dd, J ₁ = 4.8 Hz, J ₂ = 1.2 Hz, 2H), 3.99-4.07 (m, 1H), 2.52-2.65 (m, 2H), 1.97-2.17 (m, 2H) , 1.84-1.96 (m, 1H), 1.57-1.71 (m, 1H), 1.14 (s, 6H), 1.07 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 158.7, 137.7, 135.6, 134.0, 129.6,127.6, 125.8, 117.0, 93.5, 70.3, 64.8, 40.2, 26.9, 26.4, 25.6, 25.5, 23.4,19.5, 19.3; IR (film) cm ^-1 3071w, 1665w, 14854m , 1105m, 1057m, 821w, 738w, 701s, 611w. HRMS (ESI-TOF, m/z) calcd for C ₂₉ H ₃₇ NO ₂ Si (M+Na) ⁺ :482.2486, found 482.2487;

The structural formula of the intermediate product Z1-3 is as follows:

4) Preparation of intermediate product Z1-4

Using the preparation method of the intermediate product Z1 in Example 4, the corresponding crude product was obtained, which was purified by a flash silica gel column to obtain 48.8 mg of the intermediate product Z1-4 as a pale yellow liquid, and the yield was 95%;

Wherein, for the intermediate product Z1-4, [α] _D ²⁵ = +10.4° ( c = 1.0 in CHCl ₃ ); ¹ H NMR (400MHz, CDCl ₃ ) δ 7.66-7.74 (m, 4H), 7.32-7.49 ( m, 6H), 5.75-5.91 (m, 1H), 4.97-5.18 (m, 2H), 4.40 (t, J = 3.6 Hz, 1H), 3.67-3.76 (m, 1H), 3.54 (s, 2H) , 2.29-2.39 (m, 1H), 2.20-2.29 (m, 1H), 1.93-2.13 (m, 2H), 1.63-1.81 (m, 2H), 1.48 (q, J = 7.6 Hz, 4H), 1.07 (s, 9H), 0.73 (t, J = 7.2 Hz, 6H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 154.9, 135.7, 134.9, 134.1, 129.4, 127.5, 116.6, 96.0, 74.3,63.7, 47.1, 39.8, 27.1, 26.9, 23.5, 20.5, 19.5, 7.9; IR (film) cm ^-1 3071w, 2961m, 2931m, 2857w, 1700w, 1664w, 1461w, 1427w; 1109s, 1087s, 823w, 74 RMS (ESI-TOF, m/z) calcd for C ₃₀ H ₄₂ O ₂ Si (M+Na) ⁺ : 485.2846, found485.2849;

The structural formula of the intermediate product Z1-4 is as follows:

5) Preparation of intermediate product Z1-5

Using the preparation method of the intermediate product Z1 in Example 4, the corresponding crude product was obtained, which was purified by a flash silica gel column to obtain 50.1 mg of the intermediate product Z1-5 as a pale yellow liquid, and the yield was 95%;

Wherein, for the intermediate product Z1-5, [α] _D ²⁵ = +11.4° ( c = 1.0 in CHCl ₃ ); ¹ H NMR (400MHz, CDCl ₃ ) δ 7.64-7.71 (m, 4H), 7.32-7.45 ( m, 6H), 5.38-5.52 (m, 2H), 4.36(t, J = 3.6 Hz, 1H), 3.60-3.69 (m, 1H), 3.53 (s, 2H), 2.21-2.30 (m, 1H) ,2.10-2.19 (m, 1H), 1.95-2.06 (m, 2H), 1.70-1.78 (m, 2H), 1.64 (d, J = 4.8 Hz, 3H), 1.46 (q, J = 7.6 Hz, 4H) ), 1.05 (s, 9H), 0.71 (dd, J ₁ = 7.2 Hz, J ₂ = 1.2 Hz, 6H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 154.9, 135.7, 134.2, 129.4, 127.5, 127.2 ,127.1, 95.9, 74.7, 63.7, 47.0, 38.5, 29.7, 26.9, 23.6, 20.5, 19.5, 18.0, 7.9;IR (film) cm ^-1 3071w, 2957w, 2923m, 2854m, 1664w, 1088w 1085m, 822w, 738w, 700s, 609w; HRMS (ESI-TOF, m/z) calcd for C ₂₉ H ₄₀ O ₂ Si (M+Na) ⁺ :499.3003, found 499.3004;

The structural formula of the intermediate product Z1-5 is as follows:

6) Preparation of intermediate product Z1-6

Using the preparation method of the intermediate product Z1 in Example 4, the corresponding crude product was obtained, which was purified by a flash silica gel column to obtain 25.1 mg of the intermediate product Z1-6 as a pale yellow liquid, and the yield was 85%;

where, for intermediate Z1-6, [α] _D ²⁵ = +11.0° ( c = 1.0 in CHCl ₃ ); ¹ H NMR (400MHz, CDCl ₃ ) δ 7.65 (d, J = 7.5 Hz, 4H), 7.32 -7.47 (m, 6H), 4.62-4.69 (m, 1H), 3.86-3.96 (m, 1H), 3.55 (d, J = 9.2 Hz, 1H), 3.48 (d, J = 9.2 Hz, 1H), 2.47(d, J = 6.2 Hz, 2H), 2.00-2.16 (m, 2H), 1.83-1.95 (m, 1H), 1.58-1.66 (m, 1H), 1.07 (s, 6H), 1.04 (s, 9H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 157.4, 135.7, 134.1, 129.5, 127.5, 117.0, 94.7, 70.2, 69.9, 40.8, 26.8, 26.5, 23.5, 22.7, 22.7, 19.6, IR ( film) cm ^-1 2928m, 2855m, 1670w, 1427w, 1390w, 1289w, 1111s,824w, 703m; HRMS (ESI-TOF, m/z) calcd for C ₂₇ H ₃₅ NO ₂ Si (M+Na) ⁺ :456.2329 , found456.2340;

The structural formula of the intermediate product Z1-6 is as follows:

7) Preparation of intermediate product Z1-7

Using the preparation method of the intermediate product Z1 in Example 4, the corresponding crude product was obtained, which was purified by a flash silica gel column to obtain 29.2 mg of the intermediate product Z1-7, which was a pale yellow liquid, with a yield of 91%;

where, for intermediate Z1-7, [α] _D ²⁵ = +14.7° ( c = 1.0 in CHCl ₃ ); ¹ H NMR (400MHz, CDCl ₃ ) δ 7.66 (d, J = 7.0 Hz, 4H), 7.32 -7.45 (m, 6H), 4.57-4.65 (m, 1H), 4.14-4.22 (m, 1H), 4.03-4.13 (m, 2H), 3.52 (d, J = 9.2 Hz, 1H), 3.46 (d , J =9.2 Hz, 1H), 2.58 (dd, J ₁ = 14.9 Hz, J ₂ = 7.7 Hz, 1H), 2.44 (dd, J ₁ = 14.9 Hz, J ₂ = 5.8 Hz, 1H), 2.06-2.18 (m, 1H), 1.94-2.04 (m, 1H), 1.78-1.89 (m, 1H), 1.47-1.55 (m, 1H), 1.21 (t, J = 7.1 Hz, 3H), 1.05 (s, 6H) ), 1.04 (s, 9H); ¹³ CNMR (151 MHz, CDCl ₃ ) δ 171.1, 157.7, 135.6, 134.1, 129.4, 127.5, 94.1, 71.6, 70.0, 60.4, 40.8, 40.4, 27.1, 22.8.8, 2 , 20.1, 19.5, 14.2; IR (film)cm ^-1 2928m, 2855m, 1736s, 1427w, 1195w, 1111s, 824w, 703m, 611w; HRMS (ESI-TOF, m/z) calcd for C ₂₉ H ₄₀ O ₄ Si (M+Na) ⁺ : 503.2588, found 503.2603;

The structural formula of the intermediate product Z1-7 is as follows:

。

.

The above-obtained intermediate products Z1-1 to Z1-7 are used as raw materials, respectively, for the preparation of bryozoin C-ring compound analogs.

Example 6

Based on the synthesis method in Example 4, this example uses the bryozoin C-ring skeleton compounds 1-39 in Example 3 as raw materials, respectively, to provide a synthesis method for a class of bryozoin C-ring compound analogs (same as the implementation Steps Z1-Z5) in Example 4, a series of bryozoin C-ring compound analogs were obtained to further illustrate the present invention.

Example 7

Based on the synthesis method in Example 4, this example uses the intermediate product Z1-1 to the intermediate product Z1-7 in Example 5 as raw materials, respectively, to provide a synthetic method of a class of bryozoin C-ring compound analogs (same as the same Steps Z2-Z5) in Example 4, to obtain a series of bryozoin C-ring compound analogs, to further illustrate the present invention.

Example 8

Based on Examples 1-2, this example proposes the use of a class of bryophytin C-ring skeleton compounds, including using the bryophytin C-ring skeleton compound to prepare the bryophytin C-ring compound or its analogs, The obtained bryophytin C-ring compound is used to prepare bryophytin, and the obtained brynoxin C-ring compound analog is used to prepare the brynoxin analog; products of its analogs to further illustrate the present invention.

Example 9

Based on Examples 4-7, this example proposes the use of a class of bryozoin C-ring compound analogs, including the preparation of products containing the bryozoin analogs, to further illustrate the present invention.

Among them, the product is used for the treatment of anti-cancer, anti-AIDS and anti-Alzheimer's disease.

Example 10

Based on Example 4, this example proposes a pharmaceutical composition comprising a Brassin C-ring skeleton compound or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutically acceptable carrier, diluent and excipient.

Example 11

Based on Examples 4-7, this example proposes a bryozoin C-ring compound analog or a pharmaceutically acceptable salt thereof as the active ingredient, and a pharmaceutically acceptable carrier, diluent and excipient. pharmaceutical composition.

Example 12

Based on Examples 8-9, this example proposes a pharmaceutical composition consisting of a bryozoin analog or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutically acceptable carrier, diluent and excipient .

Example 13

For the synthesis method of the bryozoin C-ring skeleton compound in Example 1, this example is about the equivalent of ketene compounds, the equivalent of iodohydrocarbons, the equivalent of additives such as zinc powder, the acid binding agent in the synthesis process (TMEDA) type and equivalent, catalyst (TMEDA, AuCl ₃ ) type and equivalent, solvent and reaction time and other influencing factors are studied to further illustrate the present invention, the results obtained are as follows in Table 1:

As shown by the numbers 1-3 in the above table: when the ketene compounds are excessive, no matter how much the equivalents of additives (other substances except ketene compounds and iodo hydrocarbon compounds) are added, the reaction yield is low, When the iodine hydrocarbon compound is excessive, the yield is obviously improved;

As shown by the numbers 3-7 in the above table: the equivalent of TMEDA (base) has no obvious effect on the reaction yield, and the equivalent of Cu(II) is too low to reduce the reaction yield, and the prolongation of the reaction time is conducive to the improvement of the reaction yield, But the reaction time is too long, the contribution to the yield is not great;

As shown by the numbers 8-9 in the above table: when the Cu(II) used is replaced by Cu(I) and the solvent is changed to an ethanol-water system, a higher yield can be obtained without additional additives, and when After 8-12 h of reaction, adding the same amount of zinc powder and Cu(I) to continue the reaction can greatly improve the reaction yield, and this condition is regarded as the final optimal reaction condition.

Among them, Cu(I/II) refers to monovalent copper/divalent copper, which corresponds to CuI/Cu(OAc) ₂ in the table; the yield in the table refers to the separation yield, that is, the yield calculated after silica gel purification ; The ratio of ethanol and TPGS aqueous solution in the solvent does not need to be strictly controlled, and the effect on the reaction yield is not obvious.

Claims (5)

1. A method for synthesizing a bryodin C-ring framework compound is characterized by comprising the following steps of carrying out water-phase free radical coupling reaction on an ketene compound and an iodohydrocarbon compound, wherein the bryodin C-ring framework compound is represented by the following structural general formula (I), the ketene compound is represented by the following structural general formula (II), and the iodohydrocarbon compound is represented by the following structural general formula (III);

the method specifically comprises the following steps:

respectively adding an ketene compound, an iodo hydrocarbon compound, zinc powder, cuprous iodide, absolute ethyl alcohol and TPGS aqueous solution into a reaction device, and stirring and reacting for 8-24h at the temperature of 0-40 ℃;

adding equal amount of zinc powder, cuprous iodide, absolute ethyl alcohol and TPGS aqueous solution into the reaction tube, stirring and reacting at 0-40 ℃ for 8-24h, and adding water into the reaction device for quenching;

then, extracting with ethyl acetate, combining organic phases, drying with anhydrous sodium sulfate, and concentrating under reduced pressure; purifying with silica gel column chromatography to obtain bryodin C ring skeleton compound;

wherein the reaction process is as follows:

；

the bryodin C-ring framework compound is obtained by modifying an E-type double bond at the C25-26 position, and has a structural formula as follows:

；

the bryodin C-ring framework compound is modified by symmetrical gem-dimethyl at C18, and the structural formula is as follows:

；

wherein TBDPSO-represents tert-butyl diphenyl siloxy;

wherein TPGS in the TPGS aqueous solution is represented by the following structural formula:

。

2. the method for synthesizing the bryodin C-ring framework compound as claimed in claim 1, wherein the TPGS mass fraction in the TPGS aqueous solution is 1-5%.

3. The method for synthesizing the bryodin C-ring framework compound as claimed in claim 1, wherein the TPGS mass fraction in the TPGS aqueous solution is 2%.

4. The method for synthesizing the bryodin C-ring framework compound as claimed in claim 1, wherein the mass ratio of the ketene compound to the iodo-hydrocarbon compound is 2: 1-1:6, wherein the mass ratio of the ketene compound to the zinc powder is 1:1-1:8, and the mass ratio of the ketene compound to the cuprous iodide is 1: 0.2-1: 3.6.

5. The method for synthesizing the bryodin C-ring framework compound as claimed in claim 1, wherein the mass ratio of the ketene compound, the iodo hydrocarbon compound, the zinc powder and the cuprous iodide is 1.0: 3.0: 5.0: 1.2.