1095272-75-5Relevant academic research and scientific papers
Total synthesis of (+)-psymberin (irciniastatin A): Catalytic reagent control as the strategic cornerstone
Smith III, Amos B.,Jurica, Jon A.,Walsh, Shawn P.
, p. 5625 - 5628 (2008)
(Chemical Equation Presented) 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,0-aminal moiety. The synthesis proceeds with a longest linear sequence of 21 steps from commercially available 2,2-dimethyl-1,3-propanediol.
Total synthesis of (+)-irciniastatin A (a.k.a. psymberin) and (-)-irciniastatin B
An, Chihui,Jurica, Jon A.,Walsh, Shawn P.,Hoye, Adam T.,Smith, Amos B.
, p. 4278 - 4296 (2013/06/27)
A unified synthetic strategy to access (+)-irciniastatin A (a.k.a. psymberin) and (-)-irciniastatin B, two cytotoxic secondary metabolites, has been achieved. Highlights of the convergent strategy comprise a boron-mediated aldol union to set the C(15)-C(17) syn-syn triad, reagent control to set the four stereocenters of the tetrahydropyran core, and a late-stage Curtius rearrangement to install the acid-sensitive stereogenic N,O-aminal. Having achieved the total synthesis of (+)-irciniastatin A, we devised an improved synthetic route to the tetrahydropyran core (13 steps) compared to the first-generation synthesis (22 steps). Construction of the structurally similar (-)-irciniastatin B was then achieved via modification of a late-stage (-)-irciniastatin A intermediate to implement a chemoselective deprotection/oxidation sequence to access the requisite oxidation state at C(11) of the tetrahydropyran core. Of particular significance, the unified strategy will permit late-stage diversification for analogue development, designed to explore the biological role of substitution at the C(11) position of these highly potent tumor cell growth inhibitory molecules.
