Total synthesis of (+)-psymberin (irciniastatin A): catalytic reagent control as the strategic cornerstone.
An effective total synthesis of the marine sponge cytotoxin (+)-psymberin [irciniastatin A (1)] has been achieved. Highlights of the strategy include a Diels-Alder reaction between a bis-siloxy diene and an allene to construct the aromatic ring, a boron-mediated aldol reaction to elaborate the C(15-17) all syn stereotriad, catalytic reagent control to set the C(8, 9, 11 and 13) stereogenic centers of the tetrahydropyran core, and a late-stage Curtius rearrangement to install the sensitive N,O-aminal moiety. The synthesis proceeds with a longest linear sequence of 21 steps from commercially available 2,2-dimethyl-1,3-propanediol.
Smith
Amos B
AB
Department of Chemistry, Laboratory for Research on the Structure of Matter, and Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu
Jurica
Jon A
JA
Walsh
Shawn P
SP
D000818:Animals; D002384:Catalysis; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry; D011161:Porifera / Q000737:chemistry*; D011753:Pyrones
D003374:Coumarins; D003603:Cytotoxins; D011753:Pyrones; C498383:psymberin