Studies on the total synthesis of lactonamycin: construction of model ABCD ring systems.
Model studies on the synthesis of the tetracyclic ABCD ring system of lactonamycin (1) are described. The key step involved the double Michael addition reaction of alcohol 8 to propynoate esters to produce the BCD units 13 and 14 of the target 1. Alternatively, double Michael addition of alcohol 8 to di-tert-butyl acetylenedcarboxylate gave the corresponding BCD ring systems 36 and 37. Acid-mediated hydrolysis of the dihydroquinone monoketal units of 13 and 14 and 36 and 37 in the presence of air gave the corresponding quinones 7 and 39. These were converted into the tetracyclic ABCD units 6, 26a, 40, and 42 of lactonamycin (1) by either dihydroxylation or epoxidation and acid-catalyzed lactonization.
Henderson
David A
DA
Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, England.
Collier
Philip N
PN
Pavé
Gregoire
G
Rzepa
Paula
P
White
Andrew J P
AJ
Burrows
Jeremy N
JN
Barrett
Anthony G M
AG
D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D007211:Indoles; D009285:Naphthoquinones; C102442:lactonamycin