The first total syntheses and structural elucidation of cryptocaryol A and ayptocaryol B were achieved in 23 and 25 linear steps, respectively. The synthesis relied on the use Of a key pseudo-C, symmetric pentaol intermediate, which in a stereochemically divergent manner was converted into either enantiomer as well as diastereomers. This synthetic effort enabled the first structure-activity relationships of this class of PDCD4 stabilizing natural products.