Biodegradable compounds, method of preparation and use thereof

Abstract

The present invention relates to a caprolactone based biodegradable compound(s) of formula (I) comprising photo-cleavable groups, photo-sensitive groups or combination thereof. The present invention also relates to a method of preparing the caprolactone based biodegradable compound(s) of formula (I). In addition, the present invention relates the caprolactone biodegradable compound(s) of formula (I) useful in the pharmaceutical field in controlled release systems, drug delivery system / carrier, bioimaging, implants, etc.

Description

[0001] BIODEGRADABLE COMPOUNDS, METHOD OF PREPARATION AND USE THEREOF

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a caprolactone based biodegradable compound of formula (I) comprising photo-cleavable groups, photo-sensitive groups or combination thereof. Particularly, present invention relates to a method of preparing the caprolactone based biodegradable compound of formula (I). More particularly, the present invention relates to biodegradable polymer compound of formula (I) useful in the pharmaceutical field in controlled release systems, drug delivery system / carrier, bioimaging, implants, etc.

[0004] BACKGROUND OF THE INVENTION

[0005] References may be made to Patent “CN111234241B”, which reports a photo-stimuli-responsive biocompatible and degradable nano-polymer micelle comprising ortho -nitrobenzyl as a photocleavable group, polycaprolactone -based polymer moiety as well as triazolyl based linker moiety and the synthetic steps involve the use of stannous octoate as a catalyst for ring-opening polymerization reaction of 2-chloro-epsilon-caprolactone (to afford III) and click chemical reaction of the poly caprolacone azide (IV) with ortho-nitrobenzyl and alkyne moiety containing polymer chain (II) using cuprous bromide as a catalyst, pentamethyldiethylene triamine (PMDETA) as a ligand and N, N-dimethylformamide as a solvent, to afford the final amphiphilic block polymer. However, in this patent, the photoresponsive group is attached to the non -biodegradable acrylate backbone, which is not preferable for further use as carrier or drug delivery system.

[0006] References may be made to Patent “CN110409186B” which reports a photo-sensitive hydrophilic / hydrophobic intelligent surface material prepared by a process comprising preparing a nanofiber substrate by electrospinning of polycaprolactone, coating dopamine by polymerization under the action of hydrogen peroxide / copper sulfate on the surface of the nanofiber substrate; forming a pre -product of a Donor- Acceptor Stenhouse Adduct (DASA) by the reaction of an electron acceptor with furfural, wherein the electron acceptor can be 3-dimethyl barbituric acid or Meldrum's acid or derivatives thereof; and soaking the dopamine-coated polycaprolactone nanofiber in the n- hexane solution of the DASA pre -product, heating to 20-25 °C for 8-10 hours to obtain the photosensitive polycaprolactone nanofiber.

[0007] Photo-cleavable groups (e.g. o-nitrobenzyl, ONB) have been mainly introduced in the side chain of non-biodegradable polymers such as polyacrylates and polystyrene but very few examples in biodegradable polymers such as aliphatic polycarbonates. Similar for Donor-Acceptor Stenhouse Adduct (DASA) as photoresponsive group. Hence, there is no example on biodegradable polymer containing DASA with polycaprolactone as biodegradable entities. Also, in said published patents, the photoresponsive group is attached / introduced in the post -polymerization modification step, which is considered not preferable, and as an additional step in the polymer preparation.

[0008] Therefore, there is an unmet need in the art to develop modified monomers and polymers with better photo-responsiveness and biodegradability which is introduced while preparing the monomers / polymers, thus avoiding the post-functionalization, and such prepared polymers and other compounds thereof amount to the application as in bioimaging, as drug delivery system, etc.

[0009] OBJECTIVES OF THE INVENTION

[0010] Main object of the present invention is to provide a caprolactone based biodegradable compound of formula (I) comprising photo-cleavable groups, photosensitive groups or combination thereof.

[0011] Another object of the present invention is to provide a method of preparing the caprolactone based biodegradable compound of formula (I).

[0012] Yet another object of the present invention is to provide biodegradable polymer compound of formula (I) useful in the pharmaceutical field in controlled release systems, drug delivery system / carrier, bioimaging, implants, etc.

[0013] Yet another object of the present invention is to provide a method of preparing a functionalized products such as polyesters, polycarbonate -based copolymers and the like using the caprolactone based biodegradable compound of formula (I).

[0014] BRIEF DESCRIPTION OF FIGURES

[0015] Figure 1 illustrates UV-Vis spectra of 0.05 wt% aqueous solutions of a) Pl, b) P2 and c) P3 recorded after photoirradiation at 365 nm at various intervals. ONB group cleaved with respective time under UV irradiation.

[0016] Figure 2 illustrates release profile and fluorescence emission spectra of nile red (hydrophobic dye) encapsulated in Pl and P2 (0.1 wt% aqueous solution).

[0017] Figure 3 illustrates1H NMR spectra of P2 upon photo irradiation at 365 nm at different time intervals. Figure 4 illustrates a) Camptothecin release profile from 0.1 wt% of aqueous solution of P1-P3 at a) UV irradiation, b) pH 4 with simultaneous UV light irradiation for a 2 h interval in the 24 h period., c) pH 7.4, and pH 4., and d) only pH 5. Anti-cancer drug camptothecin released with respective UV and pH stimuli individually as well as combined.

[0018] Figure 5 shows a) Cell viability of Pl (Blank) with and without UV irradiation; and b) Cell viability of DOX-loaded polymer with and without UV irradiation and of free DOX.

[0019] Figure 6 provides a) Epifluorescence images of MDA-MB-231 cells incubated for 30 minutes with free DOX at 37 °C (Panel A) DOX-loaded micelle with UV irradiation (Panel B) and DOX-loaded micelle UV irradiation with pH 4 (Panel C). The images from left to right show a Bright field, cell nuclei stained by DAPI (blue), the fluorescence of DOX (red), overlay of the two images, all images were taken at the same exposure time for DOX. (Scale bar 10 pm); and b) Mean Fluorescence intensity of DOX quantified by Imaging Software ZEN PRO 2012 (From Carl ZEISS).

[0020] Figure 7 represents process steps for the preparation of compounds 5 and 7 of formula (I) or (IA).

[0021] Figure 8 represents process steps for the preparation of compounds Pl, P2 and P3 of formula (I) or

[0022] (IB); wherein m =10-30 and n = 10-30.

[0023] Figure 9 represents process steps for the preparation of compounds P4, P5, P6 and P7 of formula (I) or (IB); wherein x=10-120, m = 10-30 and n =10-30.

[0024] Figure 10 represents process steps for the preparation of compounds DI and D2 of formula (I) or

[0025] (IC); wherein m = 10-30, and n = 10-30.

[0026] SUMMARY OF THE INVENTION

[0027] Accordingly, present invention provides a caprolactone based biodegradable compound of formula

[0028] (I) p is in the range of 10-100; m is in the range of 0-5 ; n is in the range of 0-5;

[0029] B is o-nitrobenzyl or protected-NBoc-methylamine;

[0030] B” is DASA, azobenzene or spiropyran; q is in the range of 10-30; g is 0-5; u= 0-5;

[0031] X is -S-S-(CH2)2-O-CO-C6H5-O-(CH2)-, -S-S-(CH2)2-O-CO-C6H5-O-CH2-C^CH, -S-S- (CH2)2-O-CO-C6H5-O-(CH2)2-triazolyl-Y, or -S-S-(CH2)2-O-CO-C6H5-O-(CH2)2-triazolyl- Z;

[0032] Y is -(CH2)r-O-CO-Z, or -(CH2)2-O-CH(CH3)-O-((CH2)2-O)t-CH3; r is in the range of 1-6; t is in the range of 1-50; and

[0033] Z is polyethyleneglycol-monomethylether, G3-Polyglyceroldendrimer or TEG functionalized dendron; provided that: one or more substituents D, D”, X, Y, B& B” may be present or absent in the compound of formula (I).

[0034] In an embodiment of the present invention, the compound of formula (I) is selected from the group consisting of:

[0035] A. Formula (IA)

[0036] A-O-(CH2)m-CO-O-(CH2)n-B Formula (IA) wherein: m is in the range of 0-5; n is in the range of 0-5; and

[0037] B is o-nitrobenzyl or protected-NBoc-methylamine.

[0038] B. Formula (IB)

[0039] Formula (IB) wherein:

[0040] A is p is in the range of 10-100; m is in the range of 0-5; n is in the range of 0-5;

[0041] B is o-nitrobenzyl or protected-NBoc-methylamine;

[0042] B” is absent; -triazolyl-Y; q is in the range of 10-30; and

[0043] Y is -(CH2)2-O-CH(CH3)-O-((CH2)2-O)t-CH3; and T is in range of 1-50.

[0044] C. Formula (IC)

[0045] Formula (IC) wherein:

[0046] A is p is in the range of 10-100; m is in the range of 0-5 ; n is in the range of 0-5 ;

[0047] B is o-nitrobenzyl or protected-NBoc-methylamine;

[0048] B” is DASA, azobenzene or spiropyran;

[0049] D” is -H or absent;

[0050] X is -S-S-(CH2)2-O-CO-C6H5-O-CH2-C^CH,-S-S-(CH2)2-O-CO-C6H5-O-(CH2)2- triazolyl-Y, or -S-S-(CH2)2-O-CO-C6H5-O-(CH2)2-triazolyl-Z;

[0051] Y is -(CH2)r-O-CO-Z; r is in range of 1-6; and

[0052] Z is selected from the group consisting of polyethylene glycol monomethyl ether, G3- Polyglycerol dendrimer or TEG functionalized dendron [TEG-G3];

[0053] DASA is selected from the group consisting of Meldrums DASA, Pyra DASA or Barbituric acid DASA.

[0054] In another embodiment of the present invention, the compound of formula (I), (IA), (IB), and (IC) are monomer, polymer, copolymer, or homopolymer; and wherein when B is present, then B” is absent, and / or when B” is present, then B is absent. In yet another embodiment, present invention provides a process of preparation of compound of formula (I) or (IA) comprising the steps of: i. reacting compound of formula 1 with oxidant and solvent at room temperature in the range of 25-35°C for a period in the range of 6 to 12 h to obtain a compound of Formula 2; ii. mixing compound of formula 2 with deprotecting agent for a period in the range of 3 to 6 h to obtain a compound of Formula 3; iii. adding compound of Formula 3 with coupling agent and a solvent with stirring for a period in the range of 12 to 24 h to obtain a compound of Formula 4; iv. adding compound of Formula 4 with oxidant and a solvent or a period in the range of 12 to 24 h to obtain a compound of Formula 5 of formula (I) or (IA); v. adding compound of Formula 3 with coupling agent, base and a solvent with stirring for a period in the range of 12 to 24 h to obtain a compound of Formula 6; and vi. adding compound of Formula 6 with oxidant and a solvent or a period in the range of 12 to 24 h to obtain a compound of Formula 7 of formula (I) or (IA).

[0055] In yet another embodiment, present invention provides a process of preparation of compound of Formula (I) or (IB) comprising the steps of: i. polymerizing compound of Formula 5 [ONB -caprolactone], propargyl alcohol, a catalyst and a solvent in a preheated oil bath at temperature in the range of 95 to 150°C to obtain polymer Pl of Formula (I) or (IB); or ii. polymerizing e-Caprolactone, compound of Formula 5 [ONB -caprolactone], propargyl alcohol, a catalyst and a solvent in a preheated oil bath at temperature in the range of 95 to 150°C to obtain polymer P2 and P3 of Formula (I) or (IB).

[0056] In yet another embodiment, present invention provides a process of preparation of compound of formula (I) or (IB) comprising the steps of: i. dissolving Pl polymer, and polyethylene Glycol monomethyl ether acetal azide in presence of a catalyst, a reducing agent and a solvent at room temperature in the range of 25-35 °C for a period in the range of 24 to 36 h to obtain a compound of Formula P4 of Formula (I) or (IB); ii. dissolving polymer P2 or P3 and polyethylene Glycol monomethyl ether acetal azide in presence of a catalyst, a reducing agent and a solvent at room temperature in the range of 25-35 °C for a period in the range of 24 to 36 h to obtain a compound of Formula P5, P6 or P7 of formula (I) or (IB);

[0057] In yet another embodiment, present invention provides a process of preparation of compound of formula (I) or (IC) comprising the steps of: i. polymerizing a reaction mixture comprising e-Caprolaclone, NBoc-functionalized E- caprolactone of formula IA, and propargyl and hydroxyl containing disulfide compound, in presence of a catalyst and a solvent in a preheated oil bath at temperature in the range of 95 to 150°C for a period in the range of 10 to 12 h to obtain compound DI of formula (I) or (IC); iii. reacting DI with TEG-G3-azide Dendron and DASA by dissolving polymer DI of alkyne-terminated NBoc-substituted poly(s-caprolactone) with TEG-G3-azide in presence of a catalyst, a solvent and a reducing agent with stirring at room temperature in the range of 25-35 °C for a period in the range of 18 to 20 h to obtain an intermediate, further reacted with DASA in presence of a depreotecting agent and a solvent to finally obtain a compound D2 of formula (I) or (IC).

[0058] In yet another embodiment of the present invention, the solvent used is selected from the group consisting of dichloromethane (DCM), dimethylformamide (DMF), toluene, tetrahydrofuran (THF), 1,4-dioxane and water;

[0059] In yet another embodiment of the present invention, the base is selected from potassium tertiary butoxide (tBuOK) and sodium hydride (NaH).

[0060] In yet another embodiment of the present invention, oxidant is selected from the group consisting of pyridinium chlorochromate (PCC), Pyridinium dichromate (PDC), Potassium perchromate (K2Cr2O?) and m-chloroperbenzoic acid (m-CPBA);

[0061] In yet another embodiment of the present invention, the deprotecting reagent is selected from trifluoroacetic acid and hydrochloric acid (HC1).

[0062] In yet another embodiment of the present invention, the coupling reagent is selected from the group consisting of Ethylcarbodiimide hydrochloride, 1 -Hydroxybenzotriazole, N,N-di cyclohexyl carbodiimdie (DCC), and 4-Dimethyl aminopyridine (DMAP);

[0063] In yet another embodiment of the present invention, the catalyst is selected from the group consisting of Tin(II) 2-ethylhexanoate, copper bromide, copper sulphate, and l,8-Diazabicyclo[5.4.0]Undec-7- ene (DBU);

[0064] In yet another embodiment of the present invention, the reducing agent is selected from N- Pentamethyldiethylenetriamine(PMDETA) and ascorbic acid.

[0065] DETAILED DESCRIPTION OF THE INVENTION

[0066] The term DASA is defined as “a class of reversible photochromic molecules that absorb in the visible and near-infrared spectral regions”.

[0067] The term “biodegradable materials” or “biodegradable compound(s)” refers but not limited to polymers, monomers, copolymers, homopolymers and so on. The term "biodegradable" is art-recognized, and includes polymers, monomers, copolymers or homopolymers compositions and formulations, that are intended to degrade during use. Biodegradable polymers typically differ from non-biodegradable polymers in that the former may be degraded during use. In certain embodiments, such use involves in vivo use, such as in vivo therapy, and in other certain embodiments, such use involves in vitro use. In general, degradation attributable to biodegradability involves the degradation of a biodegradable polymer into its component subunits, or digestion, e.g., by a biochemical process, of the polymer into smaller, non-polymeric subunits. In certain embodiments, two different types of biodegradation may generally be identified. For example, one type of biodegradation may involve cleavage of bonds (whether covalent or otherwise) in the polymer backbone, in such biodegradation, monomers and oligomers typically result, and even more typically, such biodegradation occurs by cleavage of a bond connecting one or more of subunits of a polymer. In contrast, another type of biodegradation may involve cleavage of a bond (whether covalent or otherwise) internal to sidechain or that connects a side chain to the polymer backbone.

[0068] The present invention relates to a caprolactone based biodegradable compound of formula (I) comprising photo-cleavable groups, photo-sensitive groups or combination thereof. The present invention also relates to a method of preparing the caprolactone based biodegradable compound of formula (I).

[0069] The present invention relates to production of functionalized products such as polyesters, DASA (Donor-acceptor Stenhouse adducts) based copolymers, etc. using said caprolactone based biodegradable compound of formula I or specifically Formulas IA, IB and / or IC.

[0070] The present invention relates to a caprolactone based biodegradable compound of formula (I) p is in the range of 10-100; m is in the range of 0-5 ; n is in the range of 0-5 ; B is o-nitrobenzyl or protected-NBoc-methylamine;

[0071] B” is DASA, azobenzene or spiropyran; q is in the range of 10-30; g is 0-5; u= 0-5; X is -S-S-(CH2)2-O-CO-C6H5-O-(CH2)-, -S-S-(CH2)2-O-CO-C6H5-O-CH2-CSCH, -S-S-(CH2)2-O- CO-C6H5-O-(CH2)2-triazolyl-Y, or -S-S-(CH2)2-O-CO-C6H5-O-(CH2)2-triazolyl-Z;

[0072] Y is -(CH2)r-O-CO-Z, or -(CH2)2-O-CH(CH3)-O-((CH2)2-O)t-CH3; r is in the range of 1-6; t is in the range of 1-50; and Z is selected from the group consisting of polyethyleneglycol monomethylether, G3- Polyglyceroldendrimer or TEG functionalized dendron [TEG-G3]. i. TEG functionalized dendron [TEG-G3] ii. Polyethyleneglycol-monomethyl ether; where x is in range of 10-120; in. G3-Polyglycerol dendrimer

[0073] The DASA is selected from the group consisting of: wherein R is selected from the group consisting of hydrogen, (C1-C6) alkyl or (C4-C8) aryl; provided that: one or more substituents D, D”, X, Y, B & B” may be present or absent in the compound of formula (I).

[0074] The compound of formula (I) is represented by formula (IA) as:

[0075] A-O-(CH2)m-CO-O-(CH2)n-B

[0076] Formula (IA) wherein: m is in the range of 0-5 ; n is in the range of 0-5 ; and

[0077] B is o-nitrobenzyl or protected-NBoc-methylamine.

[0078] The compound of formula (I) is represented by formula (IB) as: p is in the range of 10-100; m is in the range of 0-5 ; n is in the range of 0-5 ;

[0079] B is o-nitrobenzyl or protected-NBoc-methylamine;

[0080] B” is absent;

[0081] D is -O-CH2-C ^CH or -O-CH2-triazolyl-Y;

[0082] D” is -H or -[CO(CH2)5-O]q-H; q is in the range of 10-30; and

[0083] Y is -(CH2)2-O-CH(CH3)-O-((CH2)2-O)t-CH3; and

[0084] T is in range of 1-50.

[0085] The compound of formula (I) is represented by formula (IC) as: p is in the range of 10-100; m is in the range of 0-5 ; n is in the range of 0-5 ;

[0086] B is o-nitrobenzyl or protected-NBoc-methylamine;

[0087] B” is DASA, azobenzene or spiropyran; D” is -H or absent; X is -S-S-(CH2)2-O-CO-C6H5-O-CH2-C^CH, -S-S-(CH2)2-O-CO-C6H5-O-(CH2)2-triazolyl-Y, or -S- S-(CH2)2-O-CO-C6H5-O-(CH2)2-triazolyl-Z;

[0088] Y is -(CH2)r-O-CO-Z; r is in range of 1-6; and

[0089] Z is selected from the group consisting of polyethyleneglycol monomethylether, G3- Polyglyceroldendrimer or TEG functionalized dendron [TEG-G3].

[0090] The DASA is selected from the group consisting of Meldrums DASA, Pyra DASA or Barbituric acid DASA.

[0091] The compound of formula I, IA, IB or IC are monomer, polymer, copolymer, or homopolymer.

[0092] When B is present, then B” is absent.

[0093] When B” is present, then B is absent.

[0094] The present invention provides a process of preparation of compounds 5 and 7 of formula (I) or (IA) as given in figure 7.

[0095] The present invention provides a process of preparation of a compounds Pl, P2 and P3 of formula (I) or (IB), as given in figure 8.

[0096] The present invention provides a process of preparation of a compounds P4, P5, P6 and P7 of formula (I) or (IB) as given in figure 9.

[0097] The present invention provides a process of preparation of a compounds of formula DI and D2 of formula (I) or (IC) as given in figure 10.

[0098] The solvent used is selected from the group consisting of dichloromethane (DCM), dimethylformamide (DMF), toluene, tetrahydrofuran (THF), 1,4-dioxane, and water.

[0099] The base is selected from potassium tertiary butoxide (tBuOK) and sodium hydride (NaH).

[0100] The oxidant is selected from the group consisting of pyridiniumchlorochromate (PCC), Pyridinium dichromate (PDC), Potassium perchromate (K2Cr2O7) and m-chloroperbenzoic acid (m-CPBA).

[0101] The deprotecting reagent is selected from the group consisting of trifluoroacetic acid, and hydrochloric acid (HC1).

[0102] The coupling reagent is selected from the group consisting of Ethylcarbodiimide hydrochloride, 1- Hydroxybenzotriazole, N,N-dicyclohexylcarbodiimdie (DCC), and 4-Dimethyl aminopyridine (DMAP);

[0103] The catalyst is selected from the group consisting of Tin(II) 2-ethylhexanoate, copper bromide, copper sulphate, and l,8-Diazabicyclo[5.4.0]Undec-7-ene (DBU);

[0104] The reducing agent is selected from the group consisting of N-Pentamethyldiethylenetriamine (PMDETA) and ascorbic acid; and

[0105] Reactants and reagents are selected from the group consisting of polyethylene glycol (MW=1000- 5000), pyridine para-toluene sulfonate(PPTS), PMDETA / CuBr, sodium ascorbate / CuSO4, and Triethylene glycol(TEG)-functionalized dendron.

[0106] EXAMPLES Following examples are given by way of illustration and therefore should not be construed to limit the scope of the invention.

[0107] Example 1: Synthesis of 2-Nitrobenzyl 3-((7-oxo oxepan-4-yl)oxyl)propanoate (5)

[0108] Compound 5

[0109] Compounds 1 and 2 were synthesized as per the reported procedure. [Surnar, B.; Jayakannan, M. Stimuli-Responsive Poly(Caprolactone) Vesicles for Dual Drug Delivery under the Gastrointestinal Tract. Biomacromolecules 2013, 14 (12), 4377-4387. https: / / doi.org / 10.1021 / bm401323x.]

[0110] Synthesis of tert-Butyl3-((4-Hydroxycyclohexyl)oxy)-propionate (1)

[0111] 1 ,4-Cyclohexanediol (20.0 g, 172.4 mmol) was dissolved in dry THF (300 mL) followed by addition of catalytic amount of potassium tert-butoxide (200 mg), and the mixture was stirred for 30 min under inert conditions. To this solution, tert-butyl acrylate (15.4 g, 120.6 mmol) in dry THF (50 mL) was added dropwise, and the reaction mixture was refluxed under a nitrogen atmosphere for 30 h. THF was removed using a rotavapor, and the mixture was neutralized with IN HC1 (20 mL). It was extracted with ethyl acetate, and the organic layer was dried over anhydrous Na2SO4. The solvent was evaporated, and the product was obtained as a pale coloured viscous liquid. It was further purified by passing through column chromatography using ethyl acetate :petroleum ether (15:85).

[0112] Yield: 48%?H NMR (400 MHz, CDC13) 8 ppm: 1.56 (s, 9H, -C(CH3)3, 2.07-2.28 (t, 8H, -CH2), 2.54 (t, 2H, -CH2), 3.47 (q, 2H, -CH), 3.62 (t, 2H,-CH2) ppm.13C NMR (CDC138):27.44, 29.17, 30.33, 32.54, 63.53, 63.94, 69.50, 80.43,171.08. FT-IR (KBr, cm1) 3407, 2975, 2934, 2867, 1731, 1454, 1393, 1367, 1255, 1152, 1101, 1065, 994, 953, 896, 845, 753 and 620. HRMS (ESI+): m / z [M+ Na]+Calcd For CI3H24O4 [M+]: 267.15; Found: 267.1564.

[0113] Synthesis of tert-Butyl 3-((4-Oxocyclohexyl) oxy)propanoate (2)

[0114] Compound 1 (14.0 g, 57.3 mmol) was dissolved in dry DCM (280 mL) under a nitrogen atmosphere and stirred at 25 °C. PCC (24.7 g, 114.7 mmol) was added slowly to the above solution followed by molecular sieves (4 A) to absorb the moisture. The reaction mixture was stirred for 6 h and then filtered using DCM. It was then purified by passing through silica column using (ethyl acetate petroleum ether) (10:90). The product was obtained as a colorless liquid.

[0115] Yield:73% H NMR (400 MHz, CDC13) 8 ppm: 1.42 (s, 9H, -C(CH3)3), 1.86 (m, 2H, -CH2), 2.06 (m, 2H, -CH2), 2.22 (m, 2H, -CH2), 2.55 (m, 2H, -CH2),2.48 (t, 2H, -CH2), 3.71 (m, 3H, -OCH2and - OCH).13C NMR (CDC138): 28.23, 30.60, 36.61, 37.20, 64.20, 72.9, 80.8, 170.9, 211.40. FT-IR (KBr, cm1): 2978, 2938, 2872, 1716, 1453, 1418, 1393, 1368, 1307, 1251, 1206, 1155, 1110, 1059, 959, 893, 847, 757, 686. HRMS (ESI+): m / z [M+Na]+Calcd For CI3H22O4[M+]: 265.14; Found: 265.1407.

[0116] Synthesis of 3-((4-oxocyclohexyl) propionic acid (3) Compound (2) was dissolved in dry DCM stirred at 0°C, add drop wise trifluoroacetic acid (TFA) (lOOmg / ml), stirred at 0-30 °C 3 hour. Reaction mixture evaporated at the rota-evaporator under reduced pressure. Colourless viscous liquid was obtained by1!! NMR to confirmcomplete deprotection of tBouK group. ppm: 1.92 (m, 2H, -CH2), 2.10 (m, 2H, -CH2), 2.25 (m, 2H, -CH2), 2.27 (m, 2H, -CH2), 2.57 (t, 2H, -CH2), 3.75 (t, 3H, -CH2and -CH).

[0117] Synthesis of 2-nitrobenzyl 3-((4-oxocyclohexyl)oxy)propanoate (4)

[0118] Acid Compound (3) (10 g, 53.76 mmol), DMAP (7.88 g, 64.51 mmol), EDC HC1 (12.36 g, 64.51), was stirred in DCM (100 ml), o-nitrobenzyl alcohol (9.88 g, 64.51 mmol) was added to the mixture and stirring was continued for 24h at room temperature. The reaction was allowed to reach completion as monitored by TLC. This was confirmed starting materials was consumed. The reaction mixture was quenched by DI water and Organic phase separated and solvent evaporated. The viscous liquid was purified by column chromatography (ethyl acetate:pet ether 20:80) and dried under vacuum to afford a colourless liquid.

[0119] Yield: 65%. H NMR (400 MHz, CDCI3) 8 ppm: 1.92 (m, 2H, -CH2), 2.10 (m, 2H, -CH2), 2.25 (m, 2H, -CH2), 2.27 (m, 2H, -CH2), 2.57 (t, 2H, -CH2), 3.75 (t, 3H, -CH2and -CH), 5.56 (s, 2H, -CH2), 7.35 (t, 1H, Ar), 7.61 (t, 2H, Ar), 8.09 (d, 1H, Ar).13C NMR (CDCI3 8): 25, 28, 29, 62, 76, 125, 126, 132, 136,150, 172, 210. HRMS (ESI+): m / z [M+Na]+Calc. For CI3H24O4[M+]: 321.3; Found: 322.1285.

[0120] Synthesis of 2-nitrobenzyl 3-((7-oxo oxepan-4-yl)oxyl)propanoate (5) m-CPBA (5 g, 15.57 mmol) was added to a solution of 2 (8.06 g, 46.72 mmol) in dry DCM (100 mF) under inert conditions with continuous stirring. It was followed by the addition of anhydrous NaHCCb (1.57 g, 18.69 mmol), and the reaction mixture was stirred at 25 °C for 12 h. The solvent was evaporated, and the crude was quenched with saturated aqueous solution of NaHCCb and Na2S2C>3. It was extracted with ethyl acetate, and the organic layer was dried over anhydrous Na2SO4. The solvent was evaporated, and the crude product was purified by passing over silica column using ethyl acetate and petroleum ether (30:70). The product was obtained as a colorless semi-solid.

[0121] Yield: 78%. H NMR (400 MHz, CDCI3) 8 ppm: 1.92 (m, 2H, -CH2), 2.10 (m, 2H, -CH2), 2.27 (m, 1H, -CH2), 2.57 (t, 2H, -CH2), 2.69 (m, 1H, -CH2), 3.73 (t, 3H, -CH2and -CH), 3.76 (m, 1H, -CH2), 4.38 (m, 1H, -CH2), 5.56 (s, 2H, -CH2), 7.35 (t, 1H, Ar), 7.61 (t, 2H, Ar), 8.09 (d, 1H, Ar).13C NMR (CDCI3 8): 28, 34, 35, 62, 74, 125, 129, 131, 134, 149, 172, 176. FT-IR (KBr, cm1): 747, 1221, 1526, 1729 and 3017. HRMS (ESI+): m / z [M+Na]+Calcd For CI3H24O4[M+]: 337; Found: 338.1235.

[0122] Example 2: Synthesis of 2-((tert-Butoxycarbonyl)(methyl)amino)ethyl 3-((7-oxooxepan-4- yl)oxy)propanoate (7)

[0123] Compound 7

[0124] Synthesis of 2-((tert-butoxycarbonyl)(methyl)amino)ethyl 3-((4-oxocyclohexyl)oxy)propanoate (6)

[0125] Compound 3 (5 g, 2.68 mmol), DMAP (4.92 g, 4.03mmol), EDC HC1 (7.73 g, 4.03mmol), was stirred in DCM (100 ml). Me-NBoc ethanol (6.49 g, 4.03 mmol), was added to the mixture and stirring was continued for 24 h at room temperature. The reaction was allowed to reach completion as monitored by TLC. The reaction mixture was quenched by DI water and Organic phase separated and solvent evaporated. The viscous liquid was purified by column chromatography ethyl acetate :petether (25:75) and dried under vacuum to afford a colourless liquid.

[0126] Yield: 74%?H NMR (400 MHz, CDC13) 8 ppm: 1.88 (s, 9H, -C(CH3)3), 2.04 (t, 2H, -CH2), 2.08 (m, 2H, -CH2), 2.19 (m, 2H, -CH2), 2.52 (m, 2H, -CH2), 2.56 (t, 2H, -CH2), 2.57 (s, 3H, -CH3), 3.44 (t, 2H, -CH2), 3.71 (t, 3H, -CH and -CH2), 4.76(t, 2H, -CH2).13C NMR (CDC138): 27.48, 28.06, 30.36, 32.53, 36.73, 63.56, 65.40, 69.52, 74.17, 80.43, 177.10, 210.13 HRMS (ESI+): m / z [M+Na]+Calc. For Ci7H29NO6[M+]: 343.13; Found: 344.2012.

[0127] Synthesis of 2-((tert-butoxycarbonyl)(methyl)amino)ethyl 3-((7-oxooxepan-4- yl)oxy)propanoate (7) m-CPBA (4.52 g, 26.23 mmol) was added to a solution of compound 2 (3g 08.74 mmol) in dry DCM (100 mF) under inert conditions with continuous stirring. It was followed by the addition of anhydrous NaHCO3(2.20 g, 26.23 mmol), and the reaction mixture was stirred at 25 °C for 12 h. The solvent was evaporated, and saturated aqueous solutions of NaHCO3and Na2S2O3were added. It was extracted with ethyl acetate, and the organic layer was dried over anhydrous Na2SC>4. The solvent was evaporated, and the crude product was purified by passing over silica column using ethyl acetate:petroleum ether (30:70). The product was obtained as a colorless semisolid.

[0128] Yield:(79%). H NMR (400 MHz, CDC13) 8 ppm: 1.15 (s, 9H, -C(CH3)3), 2.07-2.09 (t, 4H, -CH2), 2.10 (m, 2H, -CH2), 2.51 (m, 4H, -CH2), 2.91 (s, 3H, -CH3), 4.16 (t, 3H, -CH2), 4.19 (m, 3H, -CH and -CH2), 5.17 (t, H, -CH2).13C NMR (CDC138): 27.48, 28.06, 30.36, 32.53, 36.73, 63.56, 65.40, 69.52, 74.17, 80.43, 177.10 FT-IR (KBr, cm1): 747, 1221, 1526, 1729 and 3017. HRMS (ESI+): m / z [M+Na]+Calcd For CI7H29NO7[M]+: 359.1; Found: 360.2012.

[0129] Example 3: Synthesis of Alkyne-terminated o-nitrobenzyl functionalizedpolyf;:- caprolactone) homopolymer (Pl) (Common name: PONBCL)

[0130] In a clean and dried Schlenk tube ONB -caprolactone (compound 5, 1g, 0.002 mol), propargyl alcohol (0.008g, 0.000148 mol), Sn(Oct)2(0.0083g, 0.000147mol) and 2ml dry toluene. Polymerization was carried out in a preheated oil bath 95 °C for 12 h under inert atmosphere. The resulting homopolymer was precipitated in diethyl ether.

[0131] Yield 82% H NMR (400 MHz, CDCI3) 5 ppm: 0.75 - 0.97 (m, 46 H) 1.11 - 1.23 (m, 27 H) 1.23 - 1.46 (m, 114 H) 1.51 - 1.71 (m, 126 H) 1.71 - 1.94 (m, 60 H) 2.21 (d, 7=2.88 Hz, 14 H) 2.25 - 2.41 (m, 98 H) 2.54 (s, 7 H) 2.50 (s, 6 H) 2.65 (t, 7=5.94 Hz, 24 H) 3.38 (s, 7 H) 3.42 - 3.53 (m, 19 H) 3.56 - 3.83 (m, 249 H) 3.96 - 4.20 (m, 83 H) 5.55 (br. s„ 22 H) 7.49 (t, 7=7.57 Hz, 11 H) 7.58 - 7.71 (m, 22 H) 8.11 (d, 7=7.88 Hz, 10 H).13C NMR (CDCI3 5): 27.84, 28.66, 30.94, 34.36, 60.12, 61.87, 63.24, 124.12, 127.83, 128.05, 131.78, 132.82, 146.85, 190.42, 172.48. FTIR (cm1)3594, 2893,1735, 1455, 1354, 1263, 1151, 959, 842.

[0132] Example 4: Synthesis of Alkyne-terminated poly[(o-nitrobenzyl functionalized caprolactone)-co-(s-caprolactone)] copolymer (P2) & (P3) (Common name: PONBCL-co-CL) m= 10-30 and n = 10-30

[0133] In a dried Schlenk tube E-Caprolactone (1.82 g, 0.0159 mol), ONB -caprolactone (compound 5, 1g, 0.002 mol), propargyl alcohol (0.008g, 0.000148 mol), Sn(Oct)2 (0.0083g, 0.000147mol) and 2ml dry toluene. Polymerization was carried out in a preheated oil bath 95 °C for 12 h under inert atmosphere. The resulting co-polymer was precipitated in diethyl ether.

[0134] NMR (400 MHz, CDC13) 5 ppm: 1.25 (m, 4H, -CH2), 1.37 (m, 30H, -CH2), 1.68 (m, 60H, -CH2), 1.77 (m, 52H, -CH2), 1.80-1.94 (m, 28H, -CH2), 2.24-2.54 (m, 73H, -CO-CH2).2.64 (m, 38H, COCH^, 3.37-3.53 (m, 18H, -CH2-O), 3.55-3.83 (m, 45H, -CH2-O), 4.04 (s, 30H, -CH2-O), 4.11 (s, 36H, -CH2-O), 4.66 (br, s 2H, alkyne -CH2), 5.45-5.61 (s, 40H, Ar-CH2-O), 7.48 (m, 20H, Ar), 7.54-7.71 (m, 40H, Ar), 8.09 (m, 20H, Ar)13C NMR (CDCI3 5): 27.84, 28.66, 30.94, 34.36, 60.12, 61.87, 63.24, 124.12, 127.83, 128.05, 131.78, 132.82, 146.85, 190.42, 172.48. FTIR (cm1)3594, 2893,1735, 1455, 1354, 1263, 1151, 959, 842. A similar procedure as above explained in example 4A was followed for P3 random copolymer by varying the ratio of c-Capro lactone and ONB -caprolactone.

[0135] NMR (400 MHz, CDC13) 8 ppm: 1.37 (m, 32H, -CH2), 1.63 (m, 57H, -CH2), 1.68 (m, 8H, -CH2), 1.70-1.94 (m, 57H, -CH2), 2.20-2.43 (m, 60H, -CH2), 2.54-2.73 (m, 30H, -O-CH2).3.37-3.53 (m, 14H, -CH2), 3.61-3.81 (m, 33H, -CH2-CO), 4.04 (br, s, 30H, -CH2-O), 4.10 (br, s, 25H, -CH2-O), 4.66 (s, 2H, -CH2-O), 5.53 (br, s 28H, Ar-CH2-O), 7.48 (m, J=7.42 Hz, 14H, Ar), 7.55-7.69 (m, 28H, Ar), 8.08 (m, 11H, Ar)13C NMR (CDCI3 8): 27.84, 28.66, 30.94, 34.36, 60.12, 61.87, 63.24, 124.12, 127.83, 128.05, 131.78, 132.82, 146.85, 190.42, 172.48. FTIR (cm1)3594, 2893,1735, 1455, 1354, 1263, 1151, 959, 842.

[0136] Example 5: Synthesis of PEG-acetal-block-[poly(o-nitrobenzyl functionalized s-caprolactone)- co-poly(;:-caprolactone ) | (P5) x=10-120, m: 10-30 and n: 10-30

[0137] In a Schlenk tube, Pl, polymer (0.5g 6.66xl0-5mmol) and polyethylene Glycol monomethyl ether acetal azide (0.211g 0.0001 mmol) were dissolved in THF and purged with nitrogen gas for 30 min. and PMDETA (2eq.) were added and reaction mixture was degassed three times by freeze pump thaw cycles. Then Cu(I)Br (1 eq.) was added and again the reaction mixture was degassed three times by freeze pump thaw cycles. The reaction mixture was kept at room temperature for 18h under nitrogen flow. The crude product was purified by 3.5 kD Dialysis tubing three times wash with methanol.to remove unreacted PEG and copper catalyst.

[0138] Yield = 0.642 g (92%) H NMR (400 MHz, CDCI3) 8 ppm: 1.25 (m, 4H, -CH2), 1.37 (m, 30H, -CH2), 1.68 (m, 60H, -CH2), 1.77 (m, 52H, -CH2), 1.80-1.94 (m, 28H, -CH2), 2.24-2.54 (m, 73H, -CO-CH2). 2.64 (m, 38H, CO-CH2), 3.37-3.53 (m, 18H, -CH2-O), 3.55-3.83 (m, 178H, -CH2-O), 3.56-3.82 (m, 46H, -CH2-O) 4.04 (s, 30H, -CH2-O), 4.11 (s, 36H, -CH2-O), 5.45-5.61 (s, 40H, Ar-CH2-O), 7.48 (m, 20H, Ar), 7.54-7.71 (m, 41H, Ar), 8.09 (m, 20H, Ar)13C NMR (CDCI3 8): 27.84, 28.66, 30.94, 34.36, 60.12, 61.87, 63.24, 124.12, 127.83, 128.05, 131.78, 132.82, 146.85, 190.42, 172.48.

[0139] A similar procedure as above explained in example 5 was followed for P6 and P7 copolymer by varying the ratio of c-Capro lactone and ONB -caprolactone.

[0140] Example 6: Synthesis of Alkyne and disulfide-terminated [poly(Boc-methyl aminoethyl functionalized ;:-caprolactone)-co-poly(;:-caprolactone)| (DI)

[0141] 30, n=10-30

[0142] In a clean and dried Schlenk tube e -Caprolactone, NBoc-functionalizede-caprolactone, propargyl and hydroxyl containing disulfide compound, Sn(Oct)2 and dry toluene were taken. Polymerization was carried out by immersing in a pre-heated oil bath at 95 °C for 12 h under inert atmosphere. The resulting copolymer was precipitated in diethyl ether.

[0143] Yield= 0.8 ppm: 1.37 (m, 32H, -CH2), 1.63 (m, 57H, -CH2), 1.68 (m, 8H, -CH2), 1.70-1.94 (m, 57H, -CH2), 2.20-2.43 (m, 60H, -CH2), 2.54-2.73 (m, 30H, -O- CH2). 3.37-3.53 (m, 14H, -CH2), 3.61-3.81 (m, 33H, -CH2-CO), 4.04 (br, s, 30H, -CH2-O), 4.10 (br, s, 25H, -CH2-O), 4.66 (s, 2H, -CH2-O), 5.53 (br, s 28H, Ar-CH2-O), 7.48 (m, J=7.42 Hz, 14H, Ar), 7.55-7.69 (m, 28H, Ar), 8.08 (m, 11H, Ar)13C NMR (CDCI3 8): 27.84, 28.66, 30.94, 34.36, 60.12, 61.87, 63.24, 124.12, 127.83, 128.05, 131.78, 132.82, 146.85, 190.42, 172.48.

[0144] Example 7: Synthesis of TEG-G3functionalized-dendron-click -disulfide-poly [(DASA functionalized s-caprolactone)-co-(s-caprolactone)] (D2) m=10-30, n=10-30

[0145] In a Schlenk tube, alkyne-terminated NBoc-substituted poly(s-caprolactone) and TEG-G3-azide were dissolved in THF, purged with nitrogen gas for 30 min and PMDETA (2eq) was added. Reaction mixture was degassed three times by freeze -pump-thaw cycle. Then Cu(I)Br (leq) was added and again the reaction mixture was degassed three times by freeze -pump-thaw cycles. Then reaction mixture was stirred at room temperature for 18h under nitrogen flow and polymer was isolated by precipitation and purified by dialysis.

[0146] Yield= 0.642 g (92%) H NMR (400 MHz, CDCI3) 8 ppm: 1.25 (m, 4H, -CH2), 1.37 (m, 30H, -CH2), 1.68 (m, 60H, -CH2), 1.77 (m, 52H, -CH2), 1.80-1.94 (m, 28H, -CH2), 2.24-2.54 (m, 73H, -CO-CH2). 2.64 (m, 38H, CO-CH2), 3.37-3.53 (m, 18H, -CH2-O), 3.55-3.83 (m, 178H, -CH2-O), 3.56-3.82 (m, 46H, -CH2-O) 4.04 (s, 30H, -CH2-O), 4.11 (s, 36H, -CH2-O), 5.45-5.61 (s, 40H, Ar-CH2-O), 7.48 (m, 20H, Ar), 7.54-7.71 (m, 41H, Ar), 8.09 (m, 20H, Ar)13C NMR (CDCI3 8): 27.84, 28.66, 30.94, 34.36, 60.12, 61.87, 63.24, 124.12, 127.83, 128.05, 131.78, 132.82, 146.85, 190.42, 172.48.

[0147] Characterization of the compounds

[0148] Table 1: Characterization data of homopolymers and copolymers

[0149] Table 2: Characterization data of copolymers

[0150] Example 8: Camptothecin (CPT) anti-cancer drug release study using said prepared compound (polymer)

[0151] The stimuli-responsive in vitro release of Camptothecin from the micelle was performed in PBS of 7.4 to match the physiological condition.

[0152] 1) Only light as stimulus: Initially three polymers Pl, P2, and P3 in PBS at pH 7.4 after 2 h UV light irradiation showed a release of 49%, 42%, and 22%, respectively (refer, Fig.4a)

[0153] 2) Only pH as stimulus: CPT release at pH 7.4, at 48 h was 20%, 17%, 14% and at pH 4, at 24 h it was 68%, 63%, and 54% for Pl, P2, and P3 respectively (Fig.4c). Also, CPT release at pH 5, at 48 h was 35%, 32%, and 29% for Pl, P2, and P3 respectively (Fig.4d).

[0154] 3) pH followed by light (Dual stimuli): In PBS of pH 4 for 8 h about 10-15% of CPT was gradually released, for Pl, P2, P3 as shown in Figure 4b. This was followed by 2 h UV light irradiation of this solution. In comparison to PBS pH 4 alone with PBS pH 4 followed by 2 h UV light irradiation, ~35, 32, 22% increase in CPT release was observed for Pl, P2, and P3 respectively. After UV light irradiation the solution was left at pH 4 for 14 h and a total 78%, 59%, and 51% of drug release was observed for Pl, P2, and P3 respectively. Thus, the newly designed ONB substituted amphiphilic PEG-b-PCL block copolymers were shown to self-assemble as stable spherical nanoparticles in water and were also capable of loading water-insoluble anticancer drugs such as Camptothecin and Doxorubicin.

[0155] Example 9: Cytotoxicity

[0156] The cytotoxicity studies for free DOX, and DOX-loaded polymers were investigated in triplenegative Brest Cancer cell MDA-MB-231. The in vitro cytotoxicity assay (MTT assay) was carried out. The relative percent cell viability in the presence of different concentrations of the polymer is shown in Fig. 5a. Greater than 80% cell viability was observed up to 500 mg mL-1 with UV irradiation of polymers, which suggests excellent biocompatibility of the synthesized block copolymers. The free DOX and DOX-loaded polymer (up to 10 mg) with and without UV irradiation showed a cytotoxic effect (up to 40% cell viability) after 2 h UV irradiation (Fig.5b).

[0157] Cellular Uptake Cellular uptake of Dox into the cells was monitored by CLSM as well. Figure 6 shows that channel (c) has the highest fluorescence intensity of Dox in Pl -Dox loaded micelles with UV light irradiation in the presence of pH 4 DMEM, indicating that the cleavage of ONB linkage and acetal linkage indeed enhanced the drug release. The higher concentration of Dox released from Pl Dox-loaded polymer micelle with UV and pH 4 also resulted in more serious damage to the cells as indicated by morphology of cells.

[0158] ADVANTAGES OF THE INVENTION

[0159] • Provides efficient and better biodegradable polymers / copolymers containing photoresponsive groups.

[0160] • A caprolactone moiety with photocleavable group provides better scope in subsequent homopolymers / copolymers formation with photoresponsive groups, and with better yields and selectivity.

Claims

We Claim1. A caprolactone based biodegradable compound of formula (I)p is in the range of 10-100; m is in the range of 0-5 ; n is in the range of 0-5;B is o-nitrobenzyl or protected-NBoc-methylamine;B” is DASA, azobenzene or spiropyran;q is in the range of 10-30; g is 0-5; u= 0-5;X is -S-S-(CH2)2-O-CO-C6H5-O-(CH2)-, -S-S-(CH2)2-O-CO-C6H5-O-CH2-CSCH, -S-S- (CH2)2-O-CO-C6H5-O-(CH2)2-triazolyl-Y, or -S-S-(CH2)2-O-CO-C6H5-O-(CH2)2-triazolyl- Z;Y is -(CH2)r-O-CO-Z, or -(CH2)2-O-CH(CH3)-O-((CH2)2-O)t-CH3; r is in the range of 1-6; t is in the range of 1-50; andZ is polyethyleneglycol-monomethylether, G3-Polyglyceroldendrimer or TEG functionalized dendron; provided that: one or more substituents D, D”, X, Y, B& B” may be present or absent in the compound of formula (I).

2. The compound of formula (I) as claimed in claim 1 , wherein the compound of formula (I) is selected from the group consisting of:A. Formula (IA)A-O-(CH2)m-CO-O-(CH2)n-BFormula (IA) wherein:m is in the range of 0-5; n is in the range of 0-5; andB is o-nitrobenzyl or protected-NBoc-methylamine.B. Formula (IB)p is in the range of 10-100; m is in the range of 0-5; n is in the range of 0-5;B is o-nitrobenzyl or protected-NBoc-methylamine;B” is absent; -triazolyl-Y;q is in the range of 10-30; andY is -(CH2)2-O-CH(CH3)-O-((CH2)2-O)t-CH3; and T is in range of 1-50.C. Formula (IC)Formula (IC) wherein:A is p is in the range of 10-100; m is in the range of 0-5 ; n is in the range of 0-5 ;B is o-nitrobenzyl or protected-NBoc-methylamine;B” is DASA, azobenzene or spiropyran;D” is -H or absent;X is -S-S-(CH2)2-O-CO-C6H5-O-CH2-C^CH,-S-S-(CH2)2-O-CO-C6H5-O-(CH2)2- triazolyl-Y, or -S-S-(CH2)2-O-CO-C6H5-O-(CH2)2-triazolyl-Z;Y is -(CH2)r-O-CO-Z; r is in range of 1-6; andZ is selected from the group consisting of polyethylene glycol monomethyl ether, G3-Polyglycerol dendrimer or TEG functionalized dendron [TEG-G3];DASA is selected from the group consisting of Meldrums DASA, Pyra DASA or Barbituric acid DASA.

3. The compound of formula (I), (IA), (IB), and (IC) as claimed in any of claims 1 and 2, wherein the compound of formula I, IA, IB or IC are monomer, polymer, copolymer, or homopolymer; and wherein when B is present, then B” is absent, and / or when B” is present, then B is absent.

4. A process of preparation of compound of formula (I) or (IA) as claimed in claim 1 and 2, comprising the steps of: i. reacting compound of formula 1 with oxidant and solvent at room temperature in the range of 25-35°C for a period in the range of 6 to 12 h to obtain a compound of Formula 2; ii. mixing compound of formula 2 with deprotecting agent for a period in the range of 3 to 6 h to obtain a compound of Formula 3; iii. adding compound of Formula 3 with coupling agent and a solvent with stirring for a period in the range of 12 to 24 h to obtain a compound of Formula 4; iv. adding compound of Formula 4 with oxidant and a solvent or a period in the range of 12 to 24 h to obtain a compound of Formula 5 of formula (I) or (IA); v. adding compound of Formula 3 with coupling agent, base and a solvent with stirring for a period in the range of 12 to 24 h to obtain a compound of Formula 6; andvi. adding compound of Formula 6 with oxidant and a solvent or a period in the range of 12 to 24 h to obtain a compound of Formula 7 of formula (I) or (IA).

5. A process of preparation of compound of Formula (I) or (IB) as claimed in claim 1 and 2, comprising the steps of: i. polymerizing compound of Formula 5 [ONB-caprolactone], propargyl alcohol, a catalyst and a solvent in a preheated oil bath at temperature in the range of 95 to 150°C to obtain polymer Pl of Formula (I) or (IB); or ii. polymerizing E-Caprolactone, compound of Formula 5 [ONB-caprolactone], propargyl alcohol, a catalyst and a solvent in a preheated oil bath at temperature in the range of 95 to 150°C to obtain polymer P2 and P3 of Formula (I) or (IB).

6. A process of preparation of compound of formula (I) or (IB) as claimed in claim 1 and 2, comprising the steps of: i. dissolving Pl polymer, and polyethylene Glycol monomethyl ether acetal azide in presence of a catalyst, a reducing agent and a solvent at room temperature in the range of 25-35 °C for a period in the range of 24 to 36 h to obtain a compound of Formula P4 of Formula (I) or (IB); ii. dissolving polymer P2 or P3 and polyethylene Glycol monomethyl ether acetal azide in presence of a catalyst, a reducing agent and a solvent at room temperature in the range of 25-35 °C for a period in the range of 24 to 36 h to obtain a compound of Formula P5, P6 or P7 of formula (I) or (IB);7. A process of preparation of compound of formula (I) or (IC) as claimed in claim 1 , 3 and 4, comprising the steps of: i. polymerizing a reaction mixture comprising e-Caprolaclone, NBoc -functionalized E- caprolactone of formula IA, and propargyl and hydroxyl containing disulfide compound, in presence of a catalyst and a solvent in a preheated oil bath at temperature in the range of 95 to 150°C for a period in the range of 10 to 12 h to obtain compound DI of formula (I) or (IC); iii. reacting DI with TEG-G3-azide Dendron and DASA by dissolving polymer DI of alkyne-terminated NBoc-substituted poly(s-caprolactone) with TEG-G3-azide in presence of a catalyst, a solvent and a reducing agent with stirring at room temperature in the range of 25-35 °C for a period in the range of 18 to 20 h to obtain an intermediate, further reacted with DASA in presence of a depreotecting agent and a solvent to finally obtain a compound D2 of formula (I) or (IC).

8. The process as claimed in claims 4 to 7, whereina) the solvent used is selected from the group consisting of dichloromethane (DCM), dimethylformamide (DMF), toluene, tetrahydrofuran (THF), 1,4-dioxane and water; b) the base is selected from potassium tertiary butoxide (tBuOK) and sodium hydride (NaH).

9. The process as claimed in claims 4 to 7, wherein a) the oxidant is selected from the group consisting of pyridinium chlorochromate (PCC), Pyridinium dichromate (PDC), Potassium perchromate (IGC^O?) and m- chloroperbenzoic acid (m-CPBA); b) the deprotecting reagent is selected from trifluoroacetic acid and hydrochloric acid (HC1).

10. The process as claimed in claims 4 to 7, wherein a) the coupling reagent is selected from the group consisting of Ethylcarbodiimide hydrochloride, 1 -Hydroxybenzotriazole, N,N-dicyclohexyl carbodiimdie (DCC), and 4-Dimethyl aminopyridine (DMAP); b) the catalyst is selected from the group consisting of Tin(II) 2-ethylhexanoate, copper bromide, copper sulphate, and l,8-Diazabicyclo[5.4.0]Undec-7-ene (DBU); c) the reducing agent is selected from N-Pentamethyldiethylenetriamine(PMDETA) and ascorbic acid.

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