Photoreactive degradable polymers and methods of making the same

Abstract

The application belongs to the technical field of photodegradable polymers, and discloses a light-responsive degradable polymer and a preparation method thereof. The method comprises the following steps: performing an ene-yne metathesis reaction on monomers containing a photodegradable group, or performing a reaction on monomers containing a photodegradable group and ene-yne monomers without a light-responsive fragment through block copolymerization or random copolymerization to obtain the light-responsive degradable polymer; and the monomers containing the photodegradable group are acyclic strain monomers. The application successfully obtains a light-responsive degradable polymer with a relatively high molecular weight and controllable polymerization effect through ene-yne cascade metathesis reaction, and the method has good effects.

Description

Technical Field

[0001] This invention belongs to the technical field of organic chemistry and polymer chemistry, and discloses a photoresponsive degradable polymer and its preparation method. Background Technology

[0002] Currently, common polymerization methods include cationic polymerization, anionic polymerization, and free radical polymerization (such as atom transfer radical polymerization, ATRP), which have been widely developed and utilized. The 2005 Nobel Prize in Chemistry was awarded to Yves Chauvin, Robert H. Grubbs, and Richard R. Schrock for their development of metathesis methods in organic synthesis. Ring-opening metathesis polymerization (ROMP), as a type of olefin metathesis, has been extensively studied. It features milder reaction conditions, faster reaction rates, and better functional group tolerance, making it a living polymerization. Moreover, unlike other traditional polymerizations, polymers obtained through ROMP retain unsaturated double bonds. Essentially, ring-opening metathesis polymerization is an olefin metathesis reaction, yielding olefin polymers containing double bonds after polymerization. These polymers can be further modified post-polymerization, hydrogenated, and otherwise yielded with more diverse functions.

[0003] Ring-opening metathesis polymerization mostly uses norbornene as a monomer, extending its applications in various fields. Currently, preliminary explorations have been conducted in areas such as molecular recognition, drug delivery, fluorescence imaging, and biomaterials. However, the resulting all-carbon skeleton polyolefins are not easily degraded, causing certain pollution and harm to the environment. With its development, many scientists have developed some acid- and base-degradable polymers, but most require strong acid or strong base conditions, which has certain limitations.

[0004] This invention provides a class of photodegradable polymers that use alkenylene cascade metathesis as the polymerization method, introduce degradation groups that respond to different wavelengths, and achieve degradation in different wavelength bands under mild conditions. Summary of the Invention

[0005] To overcome the shortcomings and deficiencies of existing technologies, the present invention aims to provide a photoresponsive degradable polymer and its preparation method. This invention solves the problem of limited polymer degradability and expands the range of photoresponsive polymers by synthesizing photoresponsive polymers through the metathesis of ene-yynes. Furthermore, currently available monomer backbones are difficult to accommodate photoresponsive modules, and cascaded ene-yyne metathesis polymerization does not require ring strain; the method of this invention overcomes this problem.

[0006] The objective of this invention is achieved through the following technical solution:

[0007] A method for preparing a photoresponsive degradable polymer includes the following steps:

[0008] Monomers containing photodegradable groups are subjected to alkenylene metathesis to obtain photoresponsive degradable polymers.

[0009] The monomer containing photodegradable groups is

[0010] R1 and R2 are photodegradable groups, such as o-nitrobenzyl, anthracene, pyrene, and coumarin derivatives;

[0011] R1 is specifically...

[0012]

[0013] R2 specifically refers to Or the monomer containing photodegradable groups is

[0014]

[0015] -R4-R3, R5 is a group containing -NH-C(O)-, and R6 is O or -OC(O)-.

[0016] The -R4-R3 specifically refers to

[0017] The phenylene group is substituted at the ortho, meta, or para positions. R5 is -CH2-NH-C(O)-CH2-.

[0018] The monomer containing photodegradable groups is specifically one or more of the following structural compounds:

[0019]

[0020]

[0021] The monomer containing photodegradable groups is a monomer without ring strain.

[0022] The catalyst for the metathesis reaction of the alkenylene is a third-generation Grubbs catalyst, preferably benzenemethylene-[1,3-bis(trimethylphenyl)-2-imidazolinyl]-dichloro-bis(3-chloropyridinium)ruthenium, or benzenemethylene-[1,3-bis(trimethylphenyl)-2-imidazolinyl]-dichloro-bispyridinium.

[0023] The solvent for the reaction is THF or DCM; the reaction time is ≥5 min. After the reaction is complete, ethyl vinyl ether is added to terminate the reaction, and triethylamine is added or not (triethylamine is not added when monomers M8 or M9 are self-polymerized), and the solvent is removed.

[0024] The concentration of the monomer containing photodegradable groups in the solvent is 0.01–0.2 M. The molar ratio of the catalyst to the monomer containing photodegradable groups used in the reaction is 1:(20–100).

[0025] The monomer containing photodegradable groups is of formula I, and the general formula of the photoresponsive degradable polymer is... The wavy line on the left connects to groups derived from the catalyst;

[0026] The monomer containing photodegradable groups is of formula II, and the general formula of the photoresponsive degradable polymer is... The wavy line on the left connects to groups derived from the catalyst;

[0027] The monomer containing photodegradable groups is of formula III, and the general formula of the photoresponsive degradable polymer is... The wavy line on the left connects to groups derived from the catalyst;

[0028] The monomer containing photodegradable groups is of formula IV, and the general formula of the photoresponsive degradable polymer is [formula missing]. The wavy line on the left connects to groups derived from the catalyst.

[0029] The alkenyne metathesis reaction can also involve monomer M1 reacting with an alkenyne monomer that does not contain a photoresponsive fragment via block copolymerization or random copolymerization to obtain a photoresponsive degradation polymer. The catalyst for the reaction is a third-generation Grubbs catalyst, such as G3 or G3-Cl.

[0030] The block copolymerization refers to the reaction of an enyne monomer without photoresponsive fragments under a protective atmosphere with the aid of a catalyst, followed by the addition of monomer M1 for copolymerization to obtain a photoresponsive degradable polymer. The reaction temperature is room temperature. The enyne monomer without photoresponsive fragments is preferably of formula V.

[0031] The random copolymerization refers to the copolymerization of monomer M1 with an enyne monomer that does not contain photoresponsive fragments under a protective atmosphere, in the presence of a catalyst, to obtain a photoresponsive degradation polymer. The enyne monomer that does not contain photoresponsive fragments is preferably of formula VI.

[0032] The alkyne monomer that does not contain a photoresponsive fragment is

[0033]

[0034] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0035] 1. This invention successfully obtains a class of photoresponse-degradable polymers with high molecular weight and controllable polymerization effect through alkenylene cascade metathesis reaction.

[0036] 2. In the method of the present invention, both the polymerization of small-ring monomers and the polymerization of macro-ring monomers have good effects. Attached Figure Description

[0037] Figures 1-14 GPC curves for aggregations of M1 to M2 and M4 to M15 are shown respectively. Figure 1 Corresponding to M1 aggregation, Figure 2 Corresponding to M2 aggregation, Figure 3 Corresponding to M4 aggregation, Figure 4 Corresponding to M5 aggregation, Figure 5 Corresponding to M6 aggregation, Figure 6 Corresponding to M7 aggregation, Figure 7 Corresponding to M8 aggregation, Figure 8 Corresponding to M9 aggregation, Figure 9 Corresponding to M10 aggregation, Figure 10 Corresponding to M11 aggregation, Figure 11 Corresponding to M12 aggregation, Figure 12 Corresponding to M13 aggregation, Figure 13 Corresponding to M14 aggregation, Figure 14 Corresponding to M15 polymerization;

[0038] Figure 15 The GPC curve for block aggregation;

[0039] Figure 16 The GPC curve for random copolymerization;

[0040] Figure 17 GPC curves for P1 degradation;

[0041] Figure 18 P is the control group Bn GPC curves of degradation;

[0042] Figure 19 GPC curves for P10 degradation;

[0043] Figure 20 GPC curves for the degradation of block copolymers;

[0044] Figure 21 GPC curves for the degradation of random copolymers. Detailed Implementation

[0045] The present invention will be further described in detail below with reference to specific embodiments, but the embodiments of the present invention are not limited thereto. All solvents used in the polymerization of the present invention are derived from a solvent purification system. Ultraviolet lamp: GHUV-365.

[0046] The catalyst can be prepared by exchanging ligands between commercially available Grubbs 2nd generation catalyst and pyridine to obtain Grubbs 3rd generation catalyst, i.e., G3. Exchanging ligands between Grubbs 2nd generation catalyst and pyridine yields Grubbs 3-Cl catalyst, i.e., G3-Cl.

[0047] The method for preparing the monomer containing photodegradable groups of Formula I includes the following steps: furfuryl alcohol undergoes an Achmatowicz reaction under the action of m-CPBA to obtain a six-membered ring hemiacetal compound 1; it is dissolved in anhydrous DCM, and Boc2O and DMAP are added to obtain a Boc-protected compound 2; different nucleophiles are added, and a Tsuji-Trust reaction is carried out under the action of Pd2(dba)3 to obtain compounds 3 substituted with different photoresponsive groups; subsequently, NaBH4 and CeCl3 are added for Luche reduction to obtain compound 4; finally, a photoelectrophoresis is carried out with Mes-substituted propargylamine under the combined action of DIAD (or DEAD) and PPh3 to obtain a monomer containing two chiral centers and a well-defined stereoconfiguration. See monomers M1-M7.

[0048] The reaction equation is:

[0049]

[0050] The method for preparing the monomer containing photodegradable groups of Formula II includes the following steps: xylose reacts with Et3N, DMAP, and acetic anhydride to obtain a tetraacetyl-substituted xylose derivative; HBr is added to induce a bromination reaction, followed by an intramolecular elimination reaction under the action of DBU to obtain intermediate 5; with the addition of different nucleophiles, under the condition of boron trifluoride as a Lewis acid, Ferrier rearrangement occurs to obtain acrylone intermediate 6; then, through Luche reaction and photoelongation reaction, a monomer with a well-defined stereoconfiguration can be obtained.

[0051] The preparation methods for monomers M8 and M9 are similar, and the reaction equations are as follows:

[0052]

[0053] The preparation method of the monomer M11-13 containing photodegradable groups is similar to that of M10.

[0054] The monomers M14 and M15 containing photodegradable groups can be prepared using existing methods.

[0055] Example 1

[0056] Synthesis of monomer M1:

[0057] (1) Preparation of compound 2

[0058] Compound 1 (6.0 mmol, 1.0 eq), 2-nitrobenzyl alcohol (10.8 mmol, 1.8 eq), and PPh3 (0.6 mmol, 0.1 eq) were dissolved in anhydrous DCM (12 mL). After deoxygenation, Pd2(dba)3 (0.15 mmol, 0.025 eq) was added at 0 °C, and the reaction was carried out at room temperature for 3 h. After the reaction was completed, the reaction was terminated by adding saturated sodium bicarbonate aqueous solution, and the mixture was extracted with DCM and dried over Na2SO4. The organic phase was concentrated and then directly purified by column chromatography with a PE:EA polarity of 10:1 to obtain compound 2. Yield: 1.32 g, 88%, product was a yellow oily liquid.

[0059] The structure of compound 1: The structure of compound 2 is

[0060] The characterization tests for compound 2 are as follows:

[0061] HRMS(ESI)[M+H] + calcd.for C 12 H 12 NO5, 249.0637, found, 249.0643.

[0062] 1 H NMR (400MHz, CDCl3): δ8.09(d,J=8.2Hz,1H),7.73(d,J=7.8Hz,1H),7.66(t,J=7.6Hz,1H),7.49(t,J=7.8Hz,1H),6.95(dd,J=10.3,3.3Hz,1H) ,6.20(d,J=10.3Hz,1H),5.38(d,J=3.3Hz,1H),5.25(d,J=14.3Hz,1H),5.08(d,J=14.3Hz,1H),4.47(d,J=17.0Hz,1H),4.15(d,J=16.9Hz,1H).

[0063] 13 C NMR (100MHz, CDCl3): δ194.45,147.47,143.75,133.89,133.57,129.16,128.76,128.36,125.09,93.41,67.99,66.63.

[0064] (2) Preparation of compound 3

[0065] Compound 2 (5.28 mmol, 1.0 eq) and CeCl3 (2.11 mmol, 0.4 eq) were dissolved in DCM (5 mL) and MeOH (5 mL) and cooled to -78 °C. NaBH4 (0.22 g, 5.81 mmol, 1.1 eq) was added, and the mixture was reacted at -78 °C for 4 h. After the reaction was complete, saturated sodium bicarbonate aqueous solution was added to terminate the reaction. The mixture was extracted with DCM, dried over Na2SO4, and the organic phase was concentrated. The product was then purified by column chromatography with an eluent polarity of PE:EA = 6:1 to obtain compound 3. Yield: 1.18 g, 89%, product was a white solid. Melting point of compound 3: 95-97 °C.

[0066] The structure of compound 3:

[0067] HRMS(ESI)[M+H] + calcd.for C 12 H 14 NO5, 252.0866, found, 252.0859.

[0068] 1 H NMR (400MHz, CDCl3): δ8.05(d,J=8.2Hz,1H),7.76(d,J=7.8Hz,1H),7.63(t,J =7.6Hz,1H),7.44(t,J=7.8Hz,1H),6.06(d,J=10.3Hz,1H),5.83(dt,J=10.5, 2.0Hz,1H),5.17(d,J=14.6Hz,1H),5.07(s,1H),4.97(d,J=14.6Hz,1H),4.27 (t,J=6.8Hz,1H),3.81(dd,J=11.0,5.3Hz,1H),3.69(dd,J=11.0,8.2Hz,1H).

[0069] 13 C NMR (100MHz, CDCl3): δ147.61,134.47,133.69,133.64,129.24,128.33,127.15,124.84,94.66,67.17,53.93,53.12.

[0070] (3) Preparation of M1

[0071] Compound 3 (4.7 mmol, 1.0 eq), Mes-substituted propargylamine (4.7 mmol, 1.0 eq), and PPh3 (7.52 mmol, 1.6 eq) were dissolved in anhydrous THF (63 mL). DEAD (1.23 g, 1.5 eq) was added at 0 °C, and the reaction was carried out at room temperature for 24 h. After concentrating the organic phase, the product was directly purified by column chromatography with an eluent polarity of PE:EA = 10:1. Yield: 1.92 g, 87%, product was a yellow solid. Melting point of monomer M1: 74-76 °C. Mes-substituted propargylamine: The structure of M1 is .

[0072] The characterization tests for M1 are as follows:

[0073] HRMS(ESI)[M+H] + calcd.for C 24 H 27 N2O6S,470.1512,found,470.1512.

[0074] 1 H NMR (400MHz, CDCl3): δ8.05 (dd, J=8.2, 1.3Hz, 1H), 7.70 (d, J=7.8Hz, 1H), 7.62 (td, J=7.6,1.3Hz,1H),7.54-7.36(m,1H),6.95(s,2H),6.12(ddd,J=10.1,3.2,1.5Hz,1H ),5.96(dd,J=10.1,5.0Hz,1H),5.20-5.07(m,2H),4.95(d,J=14.5Hz,1H),4.35-4. 11(m,2H),4.11-3.89(m,3H),2.62(s,6H),2.30(s,3H),2.20-1.99(t,J=2.4Hz,1H).

[0075] 13 C NMR (100MHz, CDCl3): δ147.67,143.13,140.59,134.23,133.68,132.47,132.21,130.59,129 .21,128.43,126.71,124.91,93.19,80.18,71.73,66.97,62.48,48.19,33.36,22.93,22.12.

[0076] Example 2

[0077] Preparation of monomer M8:

[0078] (1) Preparation of compound 6

[0079] Compound 5 (3.0 mmol, 1.0 eq) and 2-nitrobenzyl alcohol 1 (3.6 mmol, 1.2 eq) were dissolved in anhydrous DCM (12 mL). BF3·OEt2 (48%) (6.0 mmol, 2.0 eq) was added at 0 °C, and the reaction was carried out in an ice bath for 30 min. After the reaction was complete, saturated sodium bicarbonate aqueous solution was added to terminate the reaction. The mixture was extracted with DCM and dried over Na2SO4. The organic phase was concentrated and then purified by column chromatography with a PE:EA polarity of 5:1. Yield: 0.62 g, 83%, product was an orange oily liquid.

[0080] Compound 5: Compound 6:

[0081] HRMS(ESI)[M+H] + calcd.for C 12 H 12 NO5, 250.0710, found, 250.0709.

[0082] 1 H NMR (400MHz, CDCl3): δ8.16-7.99(m,1H),7.75(d,J=7.8Hz,1H),7.63(t,J= 7.6Hz,1H),7.43(t,J=7.8Hz,1H),7.10(ddd,J=10.5,3.9,1.8Hz,1H),6.15( dq,J=10.5,2.3Hz,1H),5.25(dd,J=15.2,3.4Hz,1H),5.06(dd,J=15.2,3.4 Hz,1H),4.94(s,1H),4.72-4.50(m,1H),4.32(ddd,J=19.2,3.8,1.9Hz,1H).

[0083] 13 C NMR (100MHz, CDCl3): δ188.16,148.40,148.36,147.06,134.03,133.68,128.68,128.39,124.86,124.74,124.71,97.48,67.22,59.98.

[0084] (2) Preparation of compound 7

[0085] Compound 6 (2.2 mmol, 1.0 eq) and CeCl3 (0.88 mmol, 0.4 eq) were dissolved in DCM (4.5 mL) and MeOH (4.5 mL). NaBH4 (92 mg, 2.42 mmol, 1.1 eq) was added at -78 °C, and the reaction was continued at -78 °C for 4 h. After the reaction was complete, saturated sodium bicarbonate aqueous solution was added to terminate the reaction. The mixture was extracted with DCM, dried over Na2SO4, and the organic phase was concentrated. The product was then purified by column chromatography with an eluent polarity of PE:EA = 4:1. Yield: 0.5 g, 90%, product was a white solid. Melting point: 98-100 °C.

[0086] Compound 7:

[0087] HRMS(ESI)[M]calcd.for C 12 H 13 NO5,251.0794,found,251.0794.

[0088] 1 H NMR (400MHz, CDCl3): δ8.09(dd,J=8.2,1.3Hz,1H),7.84-7.71(m,1H),7.66(td,J=7.6,1.3Hz,1H),7.57-7.41(m,1H),5.86(dd,J=10.6 ,2.2Hz,1H),5.83-5.76(m,1H),5.25(d,J=14.8Hz,1H),5.07(d,J=14.9Hz,1H),5.02(d,J=3.9Hz,1H),4.27(s,1H),4.22-4.02(m,2H).

[0089] 13 C NMR (100MHz, CDCl3): δ134.13,133.89,128.98,128.52,127.43,126.04,125.02,96.89,66.72,64.41,60.85.

[0090] (3) Preparation of M8

[0091] Compound 7 (0.45 g, 1.8 mmol, 1.0 eq), Mes-substituted propargylamine (0.43 g, 1.8 mmol, 1.0 eq), and PPh3 (0.76 g, 2.88 mmol, 1.6 eq) were dissolved in anhydrous THF (24 mL, 0.075 M). DIAD (0.55 g, 0.53 mL, 2.7 mmol, 1.5 eq) was added at 0 °C, and the reaction was carried out at room temperature for 24 h. After concentrating the organic phase, the product was directly purified by column chromatography with a PE:EA polarity of 6:1. Yield: 0.74 g, 88%, product was a yellow solid. Melting point: 92-94 °C.

[0092] M8:

[0093] HRMS(ESI)[M]calcd.for C 24 H 26 N2O6S,470.1512,found,470.1514.

[0094] 1 H NMR (400MHz, CDCl3): δ8.09 (dd, J=8.2, 1.3Hz, 1H), 7.72-7.67 (m, 1H), 7.63 (t d,J=7.6,1.3Hz,1H),7.48-7.42(m,1H),6.93(s,2H),6.33-6.06(m,1H),5.75 -5.56(m,1H),5.29-5.10(m,2H),4.94(d,J=15.4Hz,1H),4.34-4.13(m,4H),4 .04(dd,J=18.4,2.5Hz,1H),2.62(s,6H),2.28(s,3H),2.11(t,J=2.4Hz,1H).

[0095] 13 C NMR (100MHz, CDCl3): δ147.13,143.08,140.67,134.42,133.94,132.56,132.19,131.42,128 .72,128.18,124.90,120.80,98.92,80.12,71.70,66.31,59.35,52.81,32.64,22.96,21.12.

[0096] Example 3

[0097] Preparation of monomer M10

[0098] (1) Preparation of compound 8

[0099] L-serine (95.2 mmol, 1.0 eq) was dissolved in methanol (96 mL, 1 M), and thionyl chloride (285.6 mmol) was added at 0 °C. The reaction was carried out at 65 °C for 18 h. The organic phase was evaporated to dryness and dissolved in anhydrous DCM (350 mL). Et3N (228.5 mmol, 2.4 eq) was added, and after 5 min, p-toluenesulfonyl chloride (104.7 mmol, 1.1 eq) was added under ice bath conditions. The reaction was carried out at room temperature for 18 h. After the reaction was completed, the reaction was terminated by adding saturated sodium chloride aqueous solution. The mixture was extracted with DCM, dried over Na2SO4, and the organic phase was concentrated. The crude product and imidazole (190.4 mmol, 2.0 eq) were dissolved in anhydrous DMF (300 mL), and TBSCl (142.8 mmol) was added at 0 °C. After the reaction was completed, the mixture was extracted with EtOAc and dried over Na2SO4. The organic phase was evaporated to dryness. The crude product, K₂CO₃ (285.6 mmol), TBAI (19.0 mmol), and 3-bromopropyne (152.3 mmol, 1.6 eq) were dissolved in CH₃CN (476 mL). After the reaction was complete, the mixture was filtered through diatomaceous earth. The organic phase was concentrated and then directly purified by column chromatography (compound 8). The polarity of the eluent was PE:EA = 4:1. Yield: 36.7 g, 85%, product was a yellow solid. Melting point: 46-48 °C.

[0100] Compound 8:

[0101] HRMS(ESI)[M+H] + calcd.for C 22 H 36 NO5SSi,454.2078,found,454.2074.

[0102] 1 H NMR (400MHz, CDCl3): δ6.92(s,2H),4.46(t,J=4.4Hz,1H),4.33(d,J=2.4Hz,2H),4.21(dd,J=10.5,3.9Hz,1H),4.13(dd ,J=10.5,5.0Hz,1H),3.64(s,3H),2.60(s,6H),2.27(s,3H),2.03(t,J=2.4Hz,1H),0.84(s,9H),0.02(d,J=7.8Hz,6H).

[0103] 13C NMR (100MHz, CDCl3): δ169.84,142.97,140.78,132.43,132.06,80.24,71. 19,62.94,59.94,52.14,34.48,25.73,22.96,21.06,18.16,-5.59,-5.84.

[0104] (2) Preparation of compound 9

[0105] Compound 8 (33.06 mmol, 1.0 eq) was dissolved in anhydrous DCM (143 mL) and cooled to -83 °C. Diisobutylaluminum hydride (46.28 mmol, 1.4 eq, 1.0 M hexane) was added, followed by isopropanol (20 mL) and Rochelle salt (50 mL) after 2.5 h. The mixture was stirred overnight at room temperature, extracted with EtOAc, and dried over Na2SO4. Ethyl diphenylphosphine (36.3 mmol, 1.1 eq) was dissolved in anhydrous THF (150 mL), and 60% NaH (1.46 g, 36.63 mmol, 1.0 eq) was added at 0 °C. After 0.5 h, the reaction solution was cooled to -78 °C. The crude product (15.7 g, 36.3 mmol, 1.1 eq) was dissolved in 100 mL of anhydrous THF and added to the solution. The reaction was continued at -78 °C for 1 h, followed by a further reaction at -10 °C for 1 h. After the reaction was complete, a saturated ammonium chloride aqueous solution was added to terminate the reaction. The product was extracted with EtOAc, dried over Na2SO4, and the organic phase was concentrated before direct column chromatography purification. The polarity of the eluent was PE:EA = 10:1. Yield: 10.3 g, 63%, the product was a colorless oily liquid.

[0106] Compound 9:

[0107] HRMS(ESI)[M+H] + calcd.for C 25 H 39 NO5SSi,494.2391,found,494.2394.

[0108] 1H NMR (400MHz, CDCl3): δ6.87 (s, 2H), 6.67 (dd, J=11.7, 8.6Hz, 1H), 5.74 (dd, J=1 1.7,1.3Hz,1H),5.35-5.23(m,1H),4.44(dd,J=18.5,2.4Hz,1H),4.21(dd,J=1 8.5,2.4Hz,1H),4.08(q,J=7.1Hz,2H),3.96-3.74(m,2H),2.54(s,6H),2.26(t ,J=2.5Hz,1H),2.24(s,3H),1.21(t,J=7.1Hz,3H),0.81(s,9H),-0.04(s,6H).

[0109] 13 C NMR (100MHz, CDCl3): δ165.31,145.11,142.59,140.66,132.50,131.88,120.60,80.62 ,72.50,63.36,60.22,56.28,32.56,25.80,22.81,20.96,18.19,14.18,-5.51,-5.78.

[0110] (3) Preparation of compound 10

[0111] Compound 9 (42.0 mmol, 1.0 eq) was dissolved in anhydrous DCM (140 mL), and diisobutylaluminum hydride (105.0 mmol, 2.5 eq, 1.0 M hexane) was added at -50 °C. After 0.5 h, isopropanol (40 mL) and Rochelle's salt (150 mL) were added, and the mixture was stirred overnight at room temperature. Extraction with EtOAc was performed, and the mixture was dried over Na2SO4. The organic phase was concentrated, and the product (compound 10) was directly purified by column chromatography with an eluent polarity of PE:EA = 5:1. Yield: 17.0 g, 90%, product was a colorless liquid.

[0112] Compound 10:

[0113] HRMS(ESI)[M+H] + calcd.for C 23 H 38 NO4SSi,452.2285,found,452.2288.

[0114] 1H NMR (400MHz, CDCl3): δ6.95(s,2H),6.21-5.76(m,2H),4.74-4.58(m,1H),4.17-4.07(m,2H),4.00(dd,J=18.5,2.5Hz,1H), 3.96-3.89(m,1H),3.81-3.68(m,2H),2.61(s,6H),2.29(s,3H),2.21(t,J=2.5Hz,1H),0.84(s,9H),0.01(d,J=1.1Hz,6H).

[0115] 13 C NMR (100MHz, CDCl3): δ143.05,140.71,133.25,132.59,132.09,126.86,80.03 ,72.57,64.23,58.04,54.78,32.71,25.89,22.85,21.02,18.34,-5.44,-5.56.

[0116] (4) Compound 12

[0117] Compound 11 (44.0 mmol, 1.1 eq), 3,4-dimethoxybenzyl alcohol (40.0 mmol, 1.0 eq), EDCI (80.0 mmol, 2.0 eq), and DMAP (20.0 mmol, 0.5 eq) were dissolved in anhydrous THF (134 mL) and reacted at room temperature for 24 h. After the reaction was complete, the mixture was extracted with EtOAc, dried over Na2SO4, and the organic phase was concentrated before direct column chromatography to purify the product. The polarity of the eluent was PE:EA = 22:1. Yield: 19.14 g, 86%, product was a white solid.

[0118] Compound 11: Compound 12:

[0119] Melting point: 98-100℃.

[0120] HRMS(ESI)[MH] - calcd.for C 23 H 22 NO6S,440.1173,found,440.1176.

[0121] 1H NMR (400MHz, CDCl3): δ8.50 (t, J=1.7Hz, 1H), 8.22 (dd, J=7.8, 1.4Hz, 1H), 8.01 (ddd,J=7.8,1.9,1.2Hz,1H),7.55(t,J=7.8Hz,1H),7.21(m,3H),7.15(m,2H), 7.03(dd,J=8.2,2.0Hz,1H),6.98(d,J=2.0Hz,1H),6.87(d,J=8.2Hz,1H),5.31 (s,2H),5.06(t,J=6.1Hz,1H),4.15(d,J=6.1Hz,2H),3.89(s,3H),3.88(s,3H).

[0122] 13 C NMR (100MHz, CDCl3): δ165.06,149.46,149.14,140.90,135.96,133.69,131.54,131.27,129.47 ,128.80,128.35,128.08,128.01,127.96,121.79,112.20,111.21,67.64,56.07,56.05,47.41.

[0123] (8) Preparation of compound 15

[0124] Compound 10 (8.0 mmol, 1.0 eq), compound 12 (8.8 mmol, 1.1 eq), and PPh3 (10.4 mmol, 1.3 eq) were dissolved in anhydrous THF (106 mL), and DEAD (9.6 mmol, 1.2 eq) was added at 0 °C. The reaction was allowed to proceed for 24 h at room temperature. After the reaction was complete, the organic phase was concentrated and the product (compound 15) was directly purified by column chromatography with a PE:EA polarity of 6:1. Yield: 5.95 g, 85%, product was an orange oily liquid.

[0125] Compound 15:

[0126] HRMS(ESI)[M+H] + calcd.for C 46 H 59 N2O9S2Si,875.3426,found,875.3425.

[0127] 1H NMR (400MHz, CDCl3): δ8.48(d,J=1.9Hz,1H),8.26(d,J=7.7Hz,1H),7.98(dd,J=8.0,1.7Hz,1H),7.60(t,J=7.7Hz ,1H),7.31-7.19(m,5H),7.04(dd,J=8.1,1.8Hz,1H),6.99(d,J=2.1Hz,1H),6.87(d,J=8.1Hz,1H),6.83(s,2H),5. 72(t,J=10.3Hz,1H),5.38-5.29(m,3H),4.42(d,J=15.1Hz,1H),4.21(dt,J=10.4,6.0Hz,1H),4.17-4.01(m,2H), 3.94-3.85(m,7H),3.77-3.58(m,4H),2.47(s,6H),2.23(s,3H),2.12(t,J=2.3Hz,1H),0.82(s,9H),-0.03(s,6H).

[0128] 13 C NMR (100MHz, CDCl3): δ165.04,149.39,149.09,142.98,141.05,140.48,135.87,1 33.60,132.70,132.10,131.56,131.36,129.75,129.54,128.67,128.46,128.41, 128.32,127.99,127.94,121.74,112.08,111.12,80.14,72.41,67.61,64.28,56.02,56.00,54.41,51.24,44.80,33.24,25.91,22.90,21.00,18.32,-5.42,-5.55.

[0129] (9) Preparation of compound 16

[0130] Compound 15 (7.67 mmol, 1.0 eq) was dissolved in anhydrous THF (32 mL), and TBAF (11.5 mmol, 1.5 eq, 1 M / THF) and AcOH (38.35 mmol, 5.0 eq) were added at 0 °C. The reaction was carried out at room temperature for 24 h. After the reaction was complete, the mixture was extracted with EtOAc and dried over Na2SO4. The organic phase was concentrated and then purified by column chromatography with a PE:EA polarity of 2:1. Yield: 5.25 g, 90%, product was a white solid. Melting point: 60-62 °C.

[0131] Compound 16:

[0132] HRMS(ESI)[M+H] + calcd.for C 40 H 45 N2O9S2,761.2561,found,761.2564.

[0133] 1 H NMR (400MHz, CDCl3): δ8.46(t,J=1.8Hz,1H),8.27(dt,J=7.9,1.4Hz,1H),7.98(dd,J=7.9,1.6Hz,1H),7.61(t,J=7.9Hz ,1H),7.34-7.27(m,3H),7.22-7.15(m,2H),7.04(dd,J=8.2,1.9Hz,1H),6.99(d,J=1.9Hz,1H),6.87(d,J=8.2Hz,1H),6 .84(s,2H),5.58-5.48(m,1H),5.36-5.28(m,3H),4.31(d,J=14.9Hz,1H),4.25-4.20(m,1H),4.15-4.03(m,2H),3.89(s ,3H),3.88(s,3H),3.86-3.74(m,2H),3.56(dd,J=12.0,5.4Hz,1H),3.48-3.38(m,2H),2.46(s,6H),2.24-2.20(s,4H).

[0134] 13 C NMR (100MHz, CDCl3): δ165.08,149.45,149.11,143.44,140.73,140.63,13 5.46,133.73,132.24,132.09,131.62,131.36,130.40,129.65,128.84,12 8.36,128.33,128.19,127.93,126.49,121.81,112.16,111.15,79.70,72. 94,67.75,62.97,56.06,56.03,55.20,51.63,44.33,32.51,22.88,21.04.

[0135] (10) Preparation of compound 17

[0136] Compound 16 (5.0 mmol, 1.0 eq), compound 14 (5.5 mmol, 1.1 eq), and EDCI (7.5 mmol, 1.5 eq) were dissolved in anhydrous DCM (25 mL), and DMAP (0.5 mmol, 0.1 eq) was added at 0 °C. The reaction was allowed to proceed for 24 h at room temperature. After the reaction was complete, the mixture was extracted with DCM and dried over Na₂SO₄. The organic phase was concentrated and then purified by column chromatography with a PE:EA polarity of 2:1. Yield: 4.11 g, 82%, product was a white solid.

[0137] Compound 14: Compound 17:

[0138] Melting point: 52-54℃.

[0139] HRMS(ESI)[M+H] + calcd.for calcd.for C 48 H 49 BrN3O 12 S2,1002.1936,found,1002.1928.

[0140] 1 H NMR (400MHz, CDCl3): δ8.48(t,J=1.8Hz,1H),8.37-8.24(m,2H),8.11(dd,J=8.4,1.8Hz,1H),8.02(dd,J=8.3,2.4Hz,2H),7.63(t,J=7.8Hz,1H ),7.32-7.17(m,5H),7.04(dd,J=8.1,2.0Hz,1H),7.00(d,J=2.0Hz,1H),6.88(d,J=8.1Hz,1H),6.82(s,2H),5.71-5.56(m,1H),5.46(ddd,J=1 1.0,8.5,4.6Hz,1H),5.34(s,2H),5.04-4.76(m,3H),4.46(dd,J=11.9,8.3Hz,1H),4.42-4.32(m,2H),4.17(d,J=14.9Hz,1H),4.08(dd,J=18. 5,2.5Hz,1H),3.97-3.90(m,1H),3.89(d,J=4.4Hz,6H),3.87-3.78(m,1 H),3.56(ddd,J=16.5,4.8,2.1Hz,1H),2.49(s,6H),2.25-2.15(m,4H).

[0141] 13C NMR (100MHz, CDCl3): δ164.91,163.89,150.58,149.39,149.07,143.26,140.45,140.4 2,135.43,134.11,133.70,133.21,132.55,132.31,132.17,131.63,131.32,130.86,1 29.60,128.75,128.30,128.11,127.92,125.29,125.12,121.69,112.10,111.14,79.16,73.25,67.61,64.52,55.99,55.97,52.04,51.97,44.85,42.20,32.65,22.77,20.94.

[0142] (11) Preparation of compound 18

[0143] Compound 17 (4.7 mmol, 1.0 eq), tert-butoxycarbonyl 6-aminohexanoic acid (5.64 mmol, 1.2 eq), and K₂CO₃ (7.05 mmol, 1.5 eq) were dissolved in acetone (23.5 mL). The mixture was stirred overnight at room temperature. After the reaction was complete, the mixture was extracted with EtOAc and dried over Na₂SO₄. The organic phase was concentrated and then purified directly by column chromatography with an eluent polarity of PE:EA = 3:2. Yield: 5.07 g, 93%, product was a yellow solid. Melting point: 48–50 °C.

[0144] Compound 18:

[0145] HRMS(ESI)[M]calcd.for C 59 H 68 N4O 16 S2,1152.4072,found,1152.4078.

[0146] 1H NMR(400MHz,CDCl3):δ8.46(t,J=1.8Hz,1H),8.26(dt,J=7.8,1.4Hz,1H),8.23(d,J=1.8Hz,1H),8.12-7.95(m,3H),7.61(t,J=7.8Hz,1H),7.29-7.22(m,3H),7.22-7.18(m,2H),7.03(dd,J=8.2,2.0Hz,1H),6.98(d,J=2.0Hz,1H),6.86(d,J=8.2Hz,1H),6.81(s,2H),5.66-5.58(m,1H),5.50-5.40(m,3H),5.33(s,2H),4.81(td,J=8.8,5.5Hz,1H),4.58(s,1H),4.45(dd,J=11.8,8.3Hz,1H),4.37-4.27(m,2H),4.15(d,J=14.9Hz,1H),4.05(dd,J=18.5,2.5Hz,1H),3.95-3.84(m,7H),3.80(ddd,J=16.6,8.5,1.5Hz,1H),3.55(ddd,J=16.6,4.7,2.0Hz,1H),3.09(q,J=6.5Hz,2H),2.47(s,6H),2.41(t,J=7.4Hz,2H),2.20(s,3H),2.17(t,J=2.4Hz,1H),1.70-1.61(m,2H),1.52-1.44(m,2H),1.39-1.30(m,2H).

[0147] 13 C NMR(100MHz,CDCl3):δ172.81,164.81,164.11,155.98,150.21,149.32,149.00,143.19,140.43,140.33,135.36,133.96,133.60,132.27,132.12,132.10,131.54,131.45,131.25,130.93,130.21,129.53,128.67,128.22,128.19,128.03,127.85,125.03,124.96,121.62,112.05,111.09,79.13,78.92,73.19,67.53,64.39,62.37,55.91,55.88,53.50,51.89,44.70,40.30,33.83,32.53,29.67,28.39,26.20,24.45,22.69,20.85.

[0148] (12) Preparation of monomer M10:

[0149] Compound 18 (4.39 mmol, 1.0 eq) was dissolved in anhydrous DCM (22 mL), followed by the addition of triethylsilane (43.9 mmol, 10.0 eq) and TFA (57.1 mmol, 13.0 eq). The reaction was allowed to proceed at room temperature for 4 hours, and the reaction solution was concentrated after dilution with acetone. The crude product and HATU (8.72 mmol, 2.0 eq) were dissolved in DMF (878 mL), and after 30 min, N,N-diisopropylethylamine (21.95 mmol, 5.0 eq) was added. After 36 h, the reaction solution was concentrated, washed successively with 1N HCl, 0.5N NaOH, and saturated brine, extracted with EtOAc, and dried over Na2SO4. The concentrated organic phase was then directly purified by column chromatography to obtain the product (monomer M10), with an eluent polarity of PE:EA = 1:1. Yield: 2.06 g, 53%, product was a white solid. Melting point: 140-142 °C.

[0150] Monomer M10:

[0151] HRMS(ESI)[M+H] + calcd.for C 45 H 49 N4O 11 S2,885.2834,found,885.2842.

[0152] 11H NMR (400 MHz, CDCl3): δ 8.43 (d, J = 1.5 Hz, 1H), 8.25 (dt, J = 7.8, 1.5 Hz, 1H), 8.17 - 8.09 (m, 3H), 7.92 (dt, J = 7.8, 1.5 Hz, 1H), 7.64 (t, J = 7.8 Hz, 1H), 7.37 - 7.30 (m, 3H), 7.30 - 7.26 (m, 1H), 7.19 (t, J = 5.9 Hz, 1H), 6.87 (s, 2H), 5.68 - 5.41 (m, 4H), 5.21 (td, J = 9.1, 5.5 Hz, 1H), 4.58 (dd, J = 11.9, 8.9 Hz, 1H), 4.45 (dd, J = 11.9, 5.6 Hz, 1H), 4.36 (d, J = 14.5 Hz, 1H), 4.25 (d, J = 14.5 Hz, 1H), 4.01 - 3.73 (m, 3H), 3.53 (dq, J = 13.2, 6.5 Hz, 1H), 3.49 - 3.41 (m, 1H), 3.19 (dq, J = 12.5, 6.1 Hz, 1H), 2.58 - 2.46 (m, 8H), 2.22 (s, 3H), 2.15 (t, J = 2.5 Hz, 1H), 1.71 (dq, J = 14.2, 7.1 Hz, 2H), 1.65 - 1.57 (m, 2H), 1.47 - 1.31 (m, 2H).

[0153] 13 13C NMR (100 MHz, CDCl3): δ 173.21, 165.32, 165.26, 150.02, 143.70, 140.84, 139.58, 132.83, 132.62, 132.34, 130.37, 130.31, 129.88, 129.72, 128.89, 128.65, 128.33, 125.12, 124.36, 124.12, 73.51, 64.87, 62.13, 53.24, 51.21, 45.44, 39.86, 33.63, 32.59, 28.69, 26.03, 24.13, 22.85, 21.07.

[0154] Example 4

[0155] Monomers M1-M7 (20-100 eq) were added to a 10 mL vial equipped with a stir bar and dissolved in deoxygenated THF at room temperature under a nitrogen atmosphere. A Grubbs third-generation (G3) initiator solution (1 eq) was prepared in another 4 mL vial. An appropriate volume of the G3 solution was rapidly added to the stirred reaction mixture containing the monomer solution using a microsyringe to bring the total monomer concentration to 0.08 M. After a specified time, polymerization was terminated by adding excess ethyl vinyl ether (EVE). The reaction mixture was stirred for 1 minute, and then triethylamine (0.1 mL) was added. The reaction mixture was then concentrated under vacuum. The polymers were characterized by GPC and 1H NMR. The polymerization results of M1-M7 are shown in Table 1. The GPC curves for the polymerization results of M1-M2 and M4-M7 are shown in... Figures 1-6 As shown.

[0156] Polymerization reaction equations for M1-M7:

[0157]

[0158] Table 1 Aggregation results of M1-M7

[0159]

[0160] [a] Calculated by 1H NMR; [b] Determined by GPC with THF as the mobile phase and polyacrylate as the standard. In the table, t represents the polymerization time, and Conv. (%) represents the conversion rate.

[0161] Example 5

[0162] Monomers M8-M9 (25-100 eq) were added to a 10 mL vial equipped with a stir bar and dissolved in deoxygenated THF at room temperature under a nitrogen atmosphere. A Grubbs third-generation (G3-Cl) initiator solution (1 eq) was prepared in another 4 mL vial. Using a microsyringe, an appropriate volume of G3-Cl solution was rapidly added to the stirred reaction mixture containing the monomer solution to bring the total monomer concentration to 0.1 M. After a specified time, polymerization was terminated by adding excess ethyl vinyl ether (EVE). The reaction mixture was stirred for 1 minute and then concentrated under vacuum. The polymerization was then carried out using GPC and... 1 The polymer was characterized by 1H NMR.

[0163] The polymerization results of M8-M9 are shown in Table 2. The GPC curves for the polymerization results of M8-M9 are shown in... Figures 7-8 As shown.

[0164] Polymerization reaction equation for M8-M9:

[0165]

[0166] Table 2 Aggregation results of M8-M9

[0167]

[0168] [a] Calculated by 1H NMR; [b] Determined by GPC with THF as the mobile phase and polyacrylate as the standard.

[0169] Example 6

[0170] Monomers M10-M15 (25-100 eq) were added to a 10 mL vial equipped with a stir bar and dissolved in deoxygenated DCM at room temperature under a nitrogen atmosphere. A Grubbs third-generation (G3) initiator solution (1 eq) was prepared in another 4 mL vial. Using a microsyringe, an appropriate volume of the G3 solution was rapidly added to the stirred reaction mixture containing the monomer solution to bring the total monomer concentration to 0.1 M. After a specified time, polymerization was terminated by adding excess ethyl vinyl ether (EVE). The reaction mixture was stirred for 1 minute, and then a certain volume of triethylamine (0.1 mL) was added. The reaction mixture was concentrated under vacuum. The polymerization was then carried out using GPC and... 1 The polymers were characterized by 1H NMR. The polymerization results of M10-M13 are shown in Tables 3, 4, and 5. The GPC curves for the polymerization results of M10-M13 are shown in... Figures 9-12 As shown in Table 6, the polymerization results of M14-M15 are shown in Table 6. The GPC curves for the polymerization results of M14-M15 are shown in Table 6. Figures 13-14 As shown.

[0171] Polymerization reaction equation for M10-M11:

[0172]

[0173] Table 3 Aggregation results of M10-M11

[0174]

[0175] [a] Calculated by 1H NMR; [b] Determined by GPC with CHCl3 as mobile phase and polystyrene as standard.

[0176] The polymerization equation for M12 is as follows:

[0177]

[0178] Table 4 Aggregation Results of M12

[0179]

[0180] [a] Calculated by 1H NMR spectroscopy; [b] Determined by GPC with CHCl3 as the mobile phase and polystyrene as the standard. Polymerization equation for M13:

[0181]

[0182] Table 5 shows the aggregation results of M13.

[0183]

[0184] [a] Calculated by 1H NMR spectroscopy; [b] Determined by GPC with CHCl3 as the mobile phase and polystyrene as the standard. Polymerization reaction equations for M14-M15:

[0185]

[0186] Table 6 shows the polymerization results of M14-M15.

[0187]

[0188] [a] Calculated by 1H NMR; [b] Determined by GPC with CHCl3 as mobile phase and polystyrene as standard.

[0189] Example 7

[0190] Block copolymerization: Monomers MBn (20 eq) and M1 (30 eq) or MBn (25 eq) and M1 (40 eq) were added to two separate 5 mL vials and dissolved in deoxygenated THF at room temperature under a nitrogen atmosphere. A Grubbs third-generation (G3) initiator solution (1 eq) was prepared in another 4 mL vial. An appropriate volume of G3 solution was rapidly added to the stirred solution containing MBn using a microsyringe to achieve a monomer concentration of 0.08 M. After stirring the reaction mixture for 6 minutes, the M1 solution was rapidly added to the reaction solution using a microsyringe to achieve a concentration of 0.08 M, and then stirred at room temperature. After 12 or 15 minutes, excess ethyl vinyl ether (EVE) was added to terminate the polymerization. The reaction mixture was stirred for 1 minute, and then a volume of triethylamine (0.1 mL) was added, followed by vacuum concentration of the reaction mixture. The polymerization was then terminated using GPC and... 1 The polymer was characterized by 1H NMR. The block polymerization results are shown in Table 7. The GPC curves for the block polymerization results are shown in... Figure 15 As shown.

[0191] Block polymerization reaction equation:

[0192]

[0193] Table 7. Block aggregation results

[0194]

[0195] [a] Calculated by 1H NMR; [b] Determined by GPC with THF as the mobile phase and polyacrylate as the standard.

[0196] Example 9

[0197] Random copolymerization: Monomers M1 and Mcarb (25 and 50 eq, respectively) were added together to a 10 mL vial equipped with a stir bar and dissolved in deoxygenated THF at room temperature under a nitrogen atmosphere. A Grubbs third-generation (3-chloropyridine ligand) initiator solution (G3-Cl) was prepared in another 4 mL vial. An appropriate volume of G3-Cl solution was rapidly added to the stirred flask containing the monomer solution using a microsyringe to bring the total monomer concentration to 0.1 M, and then stirred at 0 °C. After a specified time, polymerization was terminated by adding excess ethyl vinyl ether (EVE). The reaction mixture was stirred for 1 minute, and then a volume of triethylamine (0.1 mL) was added, followed by vacuum concentration of the reaction mixture. The polymerization was then carried out using GPC and... 1 The polymer was characterized by 1H NMR. The results of random copolymerization are shown in Table 8, and the GPC curves are as follows: Figure 16 As shown.

[0198] The reaction equation for copolymerization:

[0199]

[0200] Table 8. Results of random copolymerization

[0201]

[0202] [a] Determined by GPC with THF as the mobile phase and polyacrylate as the standard.

[0203] Degradation test:

[0204] P1 and control group P Bn The block copolymers prepared in Example 8 and the random copolymers prepared in Example 9 were subjected to photodegradation tests under a 365 nm UV lamp. The GPC degradation curves are shown below. Figure 17-21 As shown.

Claims

1. A method for preparing a photoresponsive degradable polymer, characterized in that: Includes the following steps: Monomers containing photodegradable groups are subjected to alkenylene metathesis to obtain photoresponsive degradable polymers. The monomer containing photodegradable groups is specifically one or more of the following structural compounds: 。 2. The method for preparing the photoresponsive degradable polymer according to claim 1, characterized in that: The catalyst for the alkenylene metathesis reaction is a Grubbs third-generation catalyst. The solvent for the reaction is THF or DCM; the reaction time is ≥5 min; The concentration of the monomer containing photodegradable groups in the solvent is 0.01~0.2M; the molar ratio of the catalyst used in the reaction to the monomer containing photodegradable groups is 1:(20~100).

3. The method for preparing the photoresponsive degradable polymer according to claim 2, characterized in that: The catalyst for the metathesis reaction of the alkenylene is ruthenium benzene-[1,3-bis(trimethylphenyl)-2-imidazolinyl]-dichloro-bis(3-chloropyridinium)ruthenium or ruthenium benzene-[1,3-bis(trimethylphenyl)-2-imidazolinyl]-dichloro-bispyridinium.

4. The method for preparing the photoresponsive degradable polymer according to claim 1, characterized in that: After the reaction is complete, ethyl vinyl ether is added to terminate the reaction. Triethylamine is added or not, and the solvent is removed.

5. A photoresponsive degradable polymer obtained by the preparation method according to any one of claims 1 to 4.

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