Total synthesis of (+)-irciniastatin A (a.k.a. psymberin) and (-)-irciniastatin B.

ABSTRACT: 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 chemos

SUBMITTER: An C 

PROVIDER: S-EPMC3651581 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature