Synthese totale de la (±) negamycine

摘要: Abstract A total synthesis of (±) negamycine 1 has been achieved in 14 steps from the acrolein dimer 6, which possesses same carbon skeleton as key intermediate lactone 4. Treatment 2-acetoxymethyl 3,4-dihydro[2H]pyran 8, obtained with lead tetracetate gave allylic hemiketal 15, was converted into corresponding anomeric methyl ethers 23. Hydroxylation double bond 23 mercuric acetate, occurred selectively at γ-position and resulting isomeric alcohols 24 were isolated their dimesylates 25a 25b. Condensation sodium azide (trans-derivative resulted formation cis-diazide 26a by inversion configuration C3. Hydrogenation followed acetylation diamine cis-diamide 28 having required stereochemistry. Oxidation 29 means silver silicate yielded diacetamido-lactone 4, then hydrolysed δ-hydroxy β-lysine 2 refluxing aqueous HCl. Under conditions to protect amino-groups benzylcarbamates, 30 produced. However, directly hydrazine 36 condensation benzyl N-methyl-hydrazinoacetate acetonitrile m presence SiO2. Finally hydrogenolysis protecting groups 36. The antibacterial activities racemic antibiotic have compared, vitro vivo, those natural product gentamicine C.