Total synthesis and structural confirmation of the marine natural product Dysinosin A: a novel inhibitor of thrombin and Factor VIIa.
The structure and absolute configuration of the marine antithrombotic product dysinosin A was confirmed by total synthesis. The strategy involved disconnections to three subunits, of which two were synthesized from the readily available l-glutamic acid, d-leucine, and d-mannitol. The Grubbs olefin metathesis carbocyclization reaction was utilized to prepare two intermediates.
Hanessian
Stephen
S
Department of Chemistry, Université de Montréal, C.P. 6128, Succursale Centre-ville, Québec H3C 3J7 Canada. stephen.hanessian@umontreal.ca
Margarita
Roberto
R
Hall
Adrian
A
Johnstone
Shawn
S
Tremblay
Martin
M
Parlanti
Luca
L
D000818:Animals; D015942:Factor VIIa / Q000037:antagonists & inhibitors*; D007211:Indoles / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis*; D013917:Thrombin / Q000037:antagonists & inhibitors*
D007211:Indoles; D011758:Pyrroles; D015842:Serine Proteinase Inhibitors; C470588:dysinosin A; D015942:Factor VIIa; D013917:Thrombin