Synthesis of the cytotoxic sponge metabolite haliclamine A.
A new convergent and unified synthesis of the marine natural alkaloid haliclamine A is described. The synthesis of 3-alkylpyridine monomers 8 and 9 was first achieved from a common thiophene intermediate 5. These syntheses make use of thiophene chemistry and the ability of cyclopropylcarbinols 20 and 21 to rearrange to the homoallylic bromides 22 and 23, respectively. The Zincke procedure for the synthesis of pyridinium salts was then applied to the corresponding amino derivatives 8 and 9 to give efficiently unsymmetrical bis-pyridinium macrocycle 1, whose reduction afforded haliclamine A.
Michelliza
Sophie
S
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette, France.
Al-Mourabit
Ali
A
Gateau-Olesker
Alice
A
Marazano
Christian
C
D000470:Alkaloids / Q000138:chemical synthesis*; D000818:Animals; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry*; D013876:Thiophenes / Q000737:chemistry
D000470:Alkaloids; D011725:Pyridines; D013876:Thiophenes; C472463:haliclamine A