Evolution of a gram-scale synthesis of (+)-discodermolide

An efficient, highly convergent, stereocontrolled total synthesis of the po tent antimitotic agent (+)-discodermolide (1) has been achieved on gram sca le. Key elements of the successful strategy include (1) elaboration of thre e advanced fragments from a common precursor (CP) which embodies the repeat ing stereochemical triad of the discodermolide backbone, (2) a-bond install ation of the Z trisubstituted olefin, exploiting a modified Negishi cross-c oupling reaction, (3) synthesis of a late-stage phosphonium salt utilizing high pressure, and (4) Wittig installation of the Z disubstituted olefin an d the terminal (Z)-diene.