Synthesis and complete stereochemical assignment of psymberin/irciniastatin A.
We describe a concise and flexible synthetic avenue for the preparation of compounds with structures relevant to those proposed for the novel marine-derived differential cytotoxins psymberin and irciniastatin A. Our efforts led to their complete stereochemical assignment and the notion that psymberin and irciniastatin A are identical compounds. Our total synthesis features an interesting termini-differentiating lactolization of a dialdehyde obtained from a C2-symmetrical bis-olefin precursor, a mild platinum-catalyzed hydrolysis of an epimerizable nitrile, a novel protocol to prepare sensitive methyl imidates, and a one-pot conversion of these imidates to N-acyl aminals. Starting from fragments 5-7 (prepared in 7-8 steps each, 30-49% overall yield) the synthesis of psymberin/irciniastatin A was completed in an additional 9 steps and 30% yield (17 steps longest linear sequence, 8.9% overall).
Jiang
Xin
X
Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, USA.
García-Fortanet
Jorge
J
De Brabander
Jef K
JK
D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry*; D008968:Molecular Conformation; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry*; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D003374:Coumarins; D011714:Pyrans; D011753:Pyrones; C498383:psymberin