Dehydrative cyclizations, acetyl chloride

The enantioselective total synthesis of streptazolin (609), a neutral lipophilic antibiotic isolated from cultures of Streptomyces viridochromogenes, utilizes a tandem iminium ion— vinylsilane cyclization of the tartrate-derived 607 together with intramolecular acylation as a way of achieving high stereoselectivity. Heating a mixture of 570 and ( )-4-bromo-4-(tri-methylsilyl)-3-buten-l-amine (605) followed by dehydration with acetyl chloride provides the imide (606) in reproducible yields of 90%. Reduction of 606 with sodium borohydride affords 607, which is refluxed in trifluoroacetic acid to provide, after careful purification, the single bicyclic adduct 608 in 74% yield. This is then transformed in four steps to the desired streptazolin (609) [196] (Scheme 134). 

The early antimicrobial compounds such as lucosit (219 R = Me) and globucid (219 R = Et) can be prepared by treatment of the 2-amino-l,3,4-thiadiazole with (V-acetylsulfonyl chloride in pyridine followed by deacetylation. A more recent antimicrobial compound (224) can be efficiently synthesized by the route shown in Scheme 35. The thiadiazole (220) is obtained by the usual cyclization procedure and then oximated to (221). Dehydration and the Pinner amidine synthesis followed by treatment with aminoacetaldehyde dimethyl acetal yields (222). Sulfuric acid cyclization furnishes the thiadiazoloimidazole derivative (223) which is further methylated, acetylated, nitrated and hydrolyzed to the desired (224) <69JHC(6)835). 

Dehydrative cyclization of the condensation product of 2,3,4,5-tetra-O-acetylgalactaroyl chloride with anthraiulic acid gave 1,2,3,4-tetra-O-acetyl-... 

---