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Total Synthesis of the α‐Helical Eicosapeptide Antibiotic Alamethicin
Author(s) -
Schmitt Heribert,
Jung Günther
Publication year - 1985
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.198519850210
Subject(s) - alamethicin , chemistry , high performance liquid chromatography , membrane , circular dichroism , chromatography , trichoderma viride , bilayer , natural product , nuclear magnetic resonance spectroscopy , lipid bilayer , stereochemistry , biochemistry , food science
The voltage‐dependent membrane pore‐forming polypeptide antibiotic alamethicin F 30 (Ac‐Aib‐Pro‐Aib‐Ala‐Aib‐Ala‐Gln‐Aib‐Val‐Aib‐Gly‐Leu‐Aib‐Pro‐Val‐Aib‐Aib‐Glu‐Gln‐Phl, 1 ) was synthesized by segment condensations. It was obtained free of racemate ( <0.8% D‐components) via the segments 2 – 11 ( 4a ) and 12–20 ( 3a ) using the dicyclohexylcarbodiimide/1‐hydroxybenzotriazole and the mixed anhydride methods. The intermediates were unequivocally characterized by chromatographic and physical methods including 13 C NMR, circular dichroism, and chiral phase gas chromatography. The segments 2–6 ( 5a ) and 12–20 ( 3 ) were also proven by X‐ray structure determinations. — The final product 1 (150 mg) was obtained without HPLC separations in very high purity and in crystalline form. According to all analytical data and the comparison by spectroscopy and chromatographic analyses (HPLC, DC) the product 1 is identical with the main component F 30 of the microheterogeneous antibiotic metabolite isolated from Trichoderma viride . The antibiotic activities of synthetic alamethicin ( 1 ) and the stimulating effect on calcium/calmodulin‐dependent guanylate cyclase of Paramecium are identical with those of natural alamethicin. – The uniform synthetic alamethicin ( 1 ) shows perfectly homogeneous conductance states of single pores on measurements in lipid bilayer membranes which had not been reported so far for any synthetic or purified natural preparation.