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Resins, reagents support solid phase synthesis |
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Wang Resins
Wang support is the most widely
used resin in SPOC. Attachment of carboxlic acid can be
achieved with DCC/DMAP or 2,6-dichlrobenzoyl chloride/pyridine. Cleavage of esters involves concentrated TFA or TFA-DCM to
provide the corresponding carboxylic acids. A general method of
coupling and cleaving primary, secondary and tertiary alcohols was
reported. In this method, the polymeric benzylic alcohol is
converted into the reactive Wang trichloroacetimidate, which
couples with the chosen alcohol in the presence of catalytic
amounts of mild Lewis acid. Alcohol is cleaved from the Wang resin
by treatment with 10% TFA-DCM for 30 min at ambient temperature.
Conditions under which such Wang ethers are stable include
Grignard reactions, ester sponification with lithium hydroxide,
Weinreb amide formation, Mitsunobu reactions and enolate
alkylations, as well as Heck reactions.
Merrifield Resins
The poly Merrifield resin was the standard
support for the synthesis of peptide acids by Boc SPPS. In peptide
chemistry, it is now really only used in the synthesis of small to
medium sized peptides, as the benzylic ester resin linkage is not
completely stable towards repetitive treatment with TFA.
Attachment of the C-terminal residue is generally achieved by
heating the resin in DMF with the appropriate amino acid cesium
salt in the presence of KI; although, Me4N salts,
sodium salts in THF with Bu4NF catalysis and, more
recently, zinc salts in EtOH have also been used.
Cleavage is normally effected by treatment of resin with HF or
TFMSA, or by hydrogenolysis. Alcohols can be released using
reducing agents such as DIBAL or LiBH4. Methyl esters
can be produced by transesterification with methoxide.
Resins with Functional Groups as Scavengers
Resins with functional groups can be used as
scavengers for the removal of residues of crude reaction products
by solution-phase syntheses. The use of scavenger resins makes it
possible to remove the impurities by a single filtration.
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