Total synthesis of amiclenomycin, an inhibitor of biotin biosynthesis.
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 1H 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-alpha-amino acid functionality was introduced by means of a Strecker reaction on the aldehydes 16 and 42, followed by enzymatic hydrolysis with immobilised pronase.
Mann
Stéphane
S
Laboratoire de Chimie Organique Biologique, Université Paris VI, UMR CNRS 7613, France.
Carillon
Sophie
S
Breyne
Olivier
O
Marquet
Andrée
A
D000613:Aminobutyrates / Q000138:chemical synthesis* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D001710:Biotin / Q000096:biosynthesis*; D015394:Molecular Structure
D000613:Aminobutyrates; D000900:Anti-Bacterial Agents; D001688:Biological Products; C006488:amiclenomycin; D001710:Biotin