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  • [Semisyntheses using proinsulin, II. Preparation and application of Nepsilon 29, Nepsilon 59-bis(methylsulfonylethoxycarbonyl)proinsulin (author's transl)].

[Semisyntheses using proinsulin, II. Preparation and application of Nepsilon 29, Nepsilon 59-bis(methylsulfonylethoxycarbonyl)proinsulin (author's transl)].

Hoppe-Seyler's Zeitschrift fur physiologische Chemie (1980-05-01)
E E Büllesbach, V K Naithani
ABSTRACT

Nepsilon 29, Nepsilon 59-Bis(methylsulfonylethoxycarbonyl)proinsulin was prepared from native beef proinsulin for its possible use in the semisynthesis of preproinsulin. The modification was made possible by first protecting the alpha-amino group of proinsulin either with the tert-butoxycarbonyl group, after reaction with bis(tert-butoxycarbonyl)oxide, or with the citraconyl group, after reaction with citraconic anhydride. Whereas Nalpha 1-tert-butoxycarbonylproinsulin was achieved by direct alkoxycarbonylation, Nalpha 1-citraconylproinsulin was obtained from partial deprotection of the quantitatively acylated proinsulin. The Nalpha 1-protected proinsulin derivatives were further quantitatively reacted with N-(methylsulphonylethoxycarbonyloxy)succinimide. The tert-butoxycarbonyl group was next removed by treatment with trifluoroacetic acid, or the citraconyl group removed by mild acid (pH 2.2) treatment. The resulting Nepsilon 29, Nepsilon 59-bis(methylsulphonylethoxycarbonyl)proinsulin was used in model reactions with the mixed anhydride of tert-butoxycarbonylmethionine with the aim of standardizing the coupling conditions to be used in the eventual synthesis of preproinsulin.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Di-tert-butyl dicarbonate, ReagentPlus®, 99%
Sigma-Aldrich
Di-tert-butyl dicarbonate, ≥98.0% (GC)
Sigma-Aldrich
Di-tert-butyl dicarbonate, ReagentPlus®, ≥99%
Sigma-Aldrich
Di-tert-butyl dicarbonate solution, 1.0 M in THF
Sigma-Aldrich
Di-tert-butyl dicarbonate solution, 2 M in methylene chloride
Sigma-Aldrich
Di-tert-butyl dicarbonate solution, 2 M in THF