Abstract
An efficient, straightforward and inexpensive method for selective
Boc deprotection on Rink-amide MBHA resin using tin(IV) chloride
in dichloromethane is presented. Preliminary results suggest that
the low degree of cleavage from the resin accompanying the Boc deprotection
may depend on steric hindrance associated with the resin. This method
can be useful as a selective deprotection step in solid-phase syntheses
of cyclic peptides and small molecules in which only a few Boc deprotection
steps are required.
Key words
Boc - deprotection - orthogonal protecting
groups - SPPS - SPOS - Rink-amide MBHA resin
References and Notes
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Only the first experiment, to confirm
the feasibility of applying SnCl4 for Boc deprotection
on Rink-amide MBHA resin, was performed with a freshly opened bottle
of SnCl4 . All other experiments were conducted without
prior purification of the reagent.
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In this experiment, since there was
no Boc group present, only cleavage from the resin may occur. Considering
at least one equivalent of SnCl4 is required for complete
Boc deprotection, the amount of SnCl4 reacting with the
peptide-resin amide bond is considerably higher and we
would expect a greater loss of substrate through cleavage.
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General procedure for SnCl4 -mediated
Boc deprotection on Rink-amide MBHA resin: The resin was pre-washed
with anhyd CH2 Cl2 (2 × 2
min). The resin was subsequently treated with SnCl4 (2
equiv, 0.02 M in anhyd CH2 Cl2 , 2 × 5
min). Upon addition of the deprotection solution, gas evolution
was observed due to rapid CO2 release and the resin became
a bright red color. The resin was then washed with DMF (1 × 3
min), 20% MeOH in DMF (1 × 3
min), 10% DIEA in DMF (1 × 3
min) and DMF (2 × 2 min). The initial
wash with DMF instantly restored the resin to its original color.