Stereoselective synthesis of the C4-C16 polyketide fragment of portimines A and B is reported, enabled by our previously established method for the stereoselective synthesis of syn-α,α'-dihydroxyketones. The preparation of this advanced fragment provides insights useful for the total synthesis of portimines A and B. An asymmetric Evans aldol reaction was used to install the C10-C11 adjacent stereogenic centers before incorporation of indantrione, followed by epoxidation and epoxide opening to forge the challenging syn-α,α'-dihydroxyketone functionality.