Resins for the Syntheses of Peptide Acids by Fmoc Chemistry

 

The most popular and reliable resins used for the solid phase synthesis of peptide acids by Fmoc chemistry are Wang resin and 2-chlorotrityl chloride resin. 2-Chlorotrityl chloride resin has the advantage to produce peptides free from contamination by diastereomeric side-products caused during the attachment of the first residue. For both resins, cleavage of the peptide with concurrent side-chain deprotection can be carried out by treatment with 95% trifluoroacetic acid and proper scavengers.

 

 

10001

p-Benzyloxybenzyl Alcohol resin (HMP resin)

Substitution: 0.5 - 1.2 mmole/g resin

Bead size 100- 200 mesh (polystyrene- 1% DVB)

5 g

25 g

100 g

$25

$110

$335

 

10002

p-Benzyloxybenzyl Alcohol resin (HMP resin)

Substitution: 0.5 - 1.2 mmoleg resin

Bead size 200- 400 mesh (polystyrene- 1% DVB)

5 g

25 g

100 g

$25

$110

$335

Method for attachment of the first residue to Wang resin: In a typical experiment, Wang resin (10 g, 0.74 mmol hydroxylmethyl group/g) and Fmoc-amino acid (14.7 mmol, 2 eq) are shaken in 50 ml DMF at r. t. for 15 minutes. Pyridine (2 ml, 3.3 eq) and 2,6-dichlorobenzoyl chloride (2.1 ml, 2 eq) are added successively and the suspension is shaken for 15 - 20 h. The resin is filtered and washed with methylene chloride. Any remaining hydroxyl groups of the resin are then benzoylated with benzoyl chloride (3 ml) and pyridine (3 ml) in dichloroethane (80 ml) for 2 hours. The resulting resin is filtered, wahed with DCM, DMF and methanol, and dried under vacuum. The final substitution rate can be determined photometrically from the amount of Fmoc chromophore released upon treatment of the resin with piperidine/DMF.

[1] S.-W. Wang, J. Am. Chem. Soc., 1973, 95, 1328.

[2] G. Lu, et al, J. Org. Chem., 1981, 46, 3433.

[3] P. Sieber, Tetrahedron Lett., 1987, 28, 6147.

11001

2-Chlorotrityl chloride resin

Substitution: 0.8 - 1.6 mmole/g resin

Bead size 100- 200 mesh (polystyrene- 1% DVB)

1 g

5 g

25 g

100 g

$35

$140

$575

$2,300

 

11002

2-Chlorotrityl chloride resin

Substitution: 0.8 - 1.6 mmole/g resin

Bead size 200- 400 mesh (polystyrene- 1% DVB)

1 g

5 g

25 g

100 g

$35

$140

$575

$2,300

Attachment of the Fmoc-amino acid on 2-chlorotrityl chloride resin: In a typical experiment, Fmoc-amino acid (6 mmole) and DIEA (4.4 ml, 25 mmole) are dissolved in dry dichloromethane (100 ml). A small amount of DMF is added if the acid is not completely dissolved in DCM (just enough to facilitate dissolution of the acid). The resulting solution is added to 2-chlorotrityl chloride resin (10 g, 1.1 - 1.6 mmole/g). The suspension is stirred for other 20 minutes. Subsequently methanol (10 ml) is added, and stirring is continued for other 10 minutes. The resin is filtered, washed (with 3 x DCM, 2 x DMF, 2 x methanol), and dried in vacuum. The final substitution rate can be determined photometrically from the amount of Fmoc chromophore released upon treatment of the resin with piperidine/DMF. For long term storage of the pre-loaded resin, the Fmoc group should be removed as it has been found to be more stable in the basic form.