Total Synthesis of Geldanamycin

The total synthesis of geldanamycin, a well-known polyketide that exhibited potent anticancer activity by inhibiting Hsp90, was finished in 26 long linear steps with 2.65% overall yield. High convergency of the synthesis was achieved by the disconnection between C12 and C13 that gives C5-C12 and C13-C21 fragments as major building blocks. The use of an alkynyl ketone as the precursor of the CS-C12 fragment enabled a reagent-controlled establishment of C7 chirality and a highly flexible substituent exchange at C8, making the synthetic route suitable for deep-seated structural modifications on geldanamycin.

Automated summary

The total synthesis of geldanamycin, a well-known polyketide with potent anticancer activity, was completed in 26 linear steps with an overall yield of 2.65%. High convergency was achieved by disconnecting between C12 and C13 to create C5-C12 and C13-C21 fragments, and using an alkynyl ketone as the precursor for the CS-C12 fragment allowed for reagent-controlled establishment of C7 chirality and flexible substituent exchange at C8.