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Total Synthesis of Amiclenomycin, an Inhibitor of Biotin Biosynthesis
Author(s) -
Mann Stéphane,
Carillon Sophie,
Breyne Olivier,
Marquet Andrée
Publication year - 2002
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20020118)8:2<439::aid-chem439>3.0.co;2-5
Subject(s) - chemistry , stereochemistry , cycloaddition , biosynthesis , adduct , hydrolysis , total synthesis , derivative (finance) , cis–trans isomerism , trimethylsilyl , natural product , enzyme , medicinal chemistry , organic chemistry , catalysis , financial economics , economics
We describe the first synthesis of amiclenomycin, a natural product that has been found to inhibit biotin biosynthesis and, as a consequence, to exhibit antibiotic properties. Structure 1 , with a trans relationship between the ring substituents, had previously been proposed for amiclenomycin on the basis of its 1 H NMR spectrum. We have prepared the trans and cis isomers 1 and 2 by unequivocal routes and we conclude that the natural product is in fact the cis isomer 2 . The properly substituted cyclohexadienyl rings were constructed first. A cycloaddition reaction between 1,2‐di(phenylsulfonyl)ethylene and the N ‐allyloxycarbonyl diene 13 , followed by reductive elimination of the phenylsulfinyl groups, gave the cis isomer 15 . To obtain the trans isomer, the O ‐trimethylsilyl diene was used to give the cis hydroxylated Diels–Alder adduct 33 , which was transformed into the corresponding trans amino derivative by means of a Mitsunobu reaction. The L ‐ α ‐amino acid functionality was introduced by means of a Strecker reaction on the aldehydes 16 and 42 , followed by enzymatic hydrolysis with immobilised pronase.