Synthesis of PTDM

Structure

Chemicals

Maleic anhydride, furan, 4-dimethyl aminopyridine (DMAP), 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC), methanol, 1,3-Di-Boc-2-(2-hydroxyethyl)guanidine, benzyl alcohol, ethylvinyl ether and trifluoroacetic acid (TFA)  reagent grade from Aldrich, Fluka or Acros. The HPLC grade solvents ethyl acetate, pentane and hexane are from Aldrich, Fisher Scientific or Acros and can be used as received. Tetrahydrofuran (THF) (HPLC grade, Fisher Scientific) is distilled from sodium/benzophenone under nitrogen. Dichloromethane (DCM) (HPLC grade, Fisher Scientific) is distilled from CaH2 under nitrogen.

3rd generation Grubbs catalyst (Dichloro-di(3-bromopyridino)-N,N’-Dimesitylenoimidazolino-Ru=CHPh; G3):  Sigma 682330-100MG, $64.80.

Synthesis of 2:

(i)

Dissolve maleic anhydride (100 g, 1.02 mol) in 1 L toluene, add 150 mL (140.7 g, 2.05 mol) furan

Stir the solution for 3 days according to the literature.

Filter the product (1), wash with hexanes and dry under vacuum.

A colorless powder should be obtained.

(ii) Follow the same procedure as Lienkamp et.al. with minor modifications.

Dissolve  Compound 1, 10 mol% DMAP and 1.9 equivalents of the 1,3-Di-Boc-2-ethyl guanidine in DCM.

After all components dissolved, cool down the solution to 0 ^oC in an ice bath, and then add 1 equivalent of EDC.

Stire the solution over night.

Dilute the reaction mixture with DCM.

Wash with 10% KHSO4 (3 x 25 mL) and sat. NaHCO3 solution (3x 25 mL).

Next, dry the organic phase  over Na2SO4 and filtered.

Reduce the volume of solution by vacuum evaporation.

Purify the product with a short alumina column.

Vacuum evaporation of the solvent yields the pure product 2.

The yield ranged from ~80%.

Synthesis of monomer 3b:

Synthesis of 3a:

Dissolve compound 1 and 1.5 equivalents of the benzyl alcohol  in DCM

Add   10 mol% DMAP.

Stir the reaction mixture for 3 days.

Filter the precipitate and vacuum evaporation of residual solvent to yield the pure product 3a.

The yield is ~70%.

Synthesis of 3b:

Dissolve one equivalent of compound 3a, two equivalents of methanol and 10% DMAP  in 1:1 mixture of DCM:THF.

After all components dissolved, cool down the solution  to 0 oC in an ice bath, and add one equivalent of EDC.

Stir the solution over night.

Evaporate al the solvent 

Dissolve reaction mixture in DCM

Wash with 10% KHSO4 (3 x 25 mL) and sat. NaHCO3 solution (3x 25 mL).

Dry the organic phase over Na2SO4 and filter.

Reduce the volume of solution by vacuum evaporation

Purify the product with a short alumina column.

Vacuum evaporation of the solvent yieldx the pure product 3b.

The yield ranged from ~80%.

Synthesis of PTDM-1

Synthesis of polymer 4b.

Dissolve the monomer 2 and G3-catalyst  in 1 mL DCM each and subject to three freeze-thaw cycles.

Add the monomer  in one shot to the vigorously stirring catalyst solution at room temperature.

After 60 min, end-capped the living polymer chain  with an excess of ethylvinyl ether (1 mL, 754 mg, 10.5 mmol).

Stir the solution for 2h.

After evaporation of the solvent, dissolve the crude product in 1mL THF and precipitated in pentane.

Stir the pentane solution  for an additional 15 min and left standing unperturbed for an hour at 0oC.

Collect the precipitate by a fine sinter funnel to yield product 4a.

Dissolve polymer 4a  in 2 mL DCM and 2 mL TFA for deprotection.

After stirring overnight, remove the excess acid  by azeotropic distillation with methanol.

After complete evaporation of the acid, dissove samples  in water and dialyze against RO water until the conductivity of water is ~0.1 uS.

Recover  deprotected polymers  by lyophilization.

Store the final deprotected polymer 4b from moisture  at 4 ºC.

Synthesis of PTDM-2

Synthesis of Polymer 5b.

Dissolve monomers 2, 3b and G3-catalyst in 1 mL DCM each and subject to three freeze-thaw cycles.

First, add the monomer 3b  in one shot to the vigorously stirring catalyst solution at room temperature.

After 5 min, add the monomer 2  in the reaction mixture as a second block and reacted for 60 min.

After 60 min, end-capped the living polymer chain with an excess of ethylvinyl ether (1 mL, 754 mg, 10.5 mmol).

Stir the solution for 2h.

After evaporation of the solvent, dissolve the crude product  in 1mL THF and precipitate in pentane.

Stir the pentane solution for an additional 15 min and left standing unperturbed for an hour at 0oC.

Collect the precipitate  by a fine sinter funnel to yield product 5a.

Dissolve the polymer 5a in 2 mL DCM and 2 mL TFA for deprotection.

After stirring overnight, remove the excess acid  by azeotropic distillation with methanol.

After complete evaporation of the acid, dissolve samples in water and dialyzed against RO water until the conductivity of water was ~0.1uS.

Recover  deprotected polymers  by lyophilization.

Store the final deprotected polymer 5b  protected from moisture at 4 ºC.