Synthesis of the marine sponge derived beta2-adrenoceptor agonist S1319.
[reaction: see text] The marine sponge derived beta2-adrenoceptor agonist S1319 has been synthesized following a six-step linear sequence. Central to the approach employed is the formation of a 7-lithiated-2,4-dialkoxybenzothiazole intermediate obtained via a directed-lithiation/benzyne-mediated cyclization reaction. The incorporation of a tert-butyl ether residue into the cyclization precursor for the pivotal ring-closing step has been shown to significantly increase the efficiency of the reaction by the suppression of a competing directed ortho-lithiation reaction.
Fairhurst
Robin A
RA
Novartis Institutes for BioMedical Research, Novartis Respiratory Research Centre, Wimblehurst Road, Horsham, West Sussex, RH12 5AB, United Kingdom. robin.fairhurst@pharma.novartis.com
Janus
Diana
D
Lawrence
Annabel
A
D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D000818:Animals; D052160:Benzothiazoles; D003500:Cyclization; D004983:Ethanolamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification
C120088:4-hydroxy-7-(1-(1-hydroxy-2-methylamino)ethyl)-1,3-benzothiazole-2(3H)-one; D000318:Adrenergic beta-Agonists; D052160:Benzothiazoles; D004983:Ethanolamines; D013844:Thiazoles