Ircinal-related alkaloids

New approaches to total synthesis of manzamine A, ircinal A, and related alkaloids 99YGK1004. 

Ircinal B (70) and Ircinol B (71). The tetracyclic precursors of 65-69, ircinal B (70) [65] and ircinol B (71) [68], were isolated from two different Okinawan sponges, Ircinia sp. and Amphimedon sp., respectively. Surprisingly, the alcohol congener possessed the opposite absolute configuration to that of ircinal B and the aforementioned manzamine related alkaloids. Halicyclamines A (72) and B (73), halyclonacyclamines A... 

Nakadomarin A (4) (Fig. 8) was first isolated from the Okinawan marine sponge Amphimedon sp. (SS-264) by Kobayashi and coworkers in 1997 [105,106]. Nakadomarin A is considered to be a novel manzamine-related alkaloid which contains a unique 6/5/5/5/8/15 ring system involving a furan ring. The biological transformation of ircinal A to nakadomarin A was proposed (Scheme 19) [106]. 

Rao KV, Donia MS, Peng J, Garcia-Palomero E, Alonso D, Martinez A, Medina M, Franzblau SG, Tekwani BL, Khan SI, Wahyuono S, Willett KL, Hamann MT. Manzamine B and E and ircinal A related alkaloids from an Indonesian Acanthostrongylophora sponge and their activity against infectious, tropical parasitic and Alzheimer s diseases. J. Nat. Prod. 2006 69(7) 1034-1040. 

Scheme 25 Sequential formation of 13- and 8-membered azacycles in Martin s total synthesis of ircinal A (129) and related manzamine alkaloids [78]...

For a total synthesis of ircinal A and related manzamine alkaloids via RCM, see Scheme 25... 

S.F. Martin and co-workers utilized a double Swern oxidation in their synthesis of ircinal A and related manzamine alkaloids. The advanced tricyclic did intermediate was first subjected to the Swern oxidation conditions at -78 °C to afford the corresponding dialdehyde in excellent yield. In the next step, the dialdehyde was exposed to excess Wittig reagent under salt-free conditions to form the two terminal alkenes. 

The enantioselective syntheses of ircinol A (38) and the related manzamine alkaloids ircinal A and manzamine A were accomplished by Martin (Scheme 5.4.9). The concise synthesis of ircinol A (38) highlights the strategy for assembling the tricyclic ABC ring core via a domino Stille coupling/Diels-Alder reaction. 

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