Utility of polymer-supported reagents in the total synthesis of lamellarins.
Four solid-supported reagents have been utilized in the multistep synthesis of lamellarins. The use of Amberlyst A-26 Br(3)(-) and polymer bound pyridine hydrobromide perbromide (PVPHP) for keto alpha-bromination of the less studied ortho-substituted acetophenone derivatives selectively furnished the corresponding monobromination products (phenacyl bromide derivatives), which were used directly in condensation reactions with benzyldihydroisoquinoline mediated by Amberlyst A-26 NaCO(3)(-). The 2H-pyrrole carbonates subsequently underwent intramolecular Friedel-Crafts transacylation followed by lactonization to provide the lamellarin skeleton. Alternatively, Amberlyst A-26 NaCO(3)(-) effectively served as base in condensation reaction of benzyldihydroisoquinoline with alpha-nitrocinnamate derivatives to provide the corresponding 2-ethoxycarbonyl pyrroles, which smoothly underwent O-debenzylation reaction followed by lactonization to furnish the lamellarin skeleton. The novel Amberlyst-15 mediated lactonization reactions effectively combined the otherwise two separate steps into a single transformation.
Ploypradith
Poonsakdi
P
Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Vipavadee-Rangsit Highway, Bangkok 10210, Thailand. poonsakdi@tubtim.cri.or.th
Kagan
Rachel Kirk
RK
Ruchirawat
Somsak
S
D000470:Alkaloids / Q000138:chemical synthesis*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003374:Coumarins / Q000138:chemical synthesis*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D015394:Molecular Structure
D000470:Alkaloids; D003374:Coumarins; D006576:Heterocyclic Compounds, 4 or More Rings; C489096:lamellarin alpha