Optical clocks with an unprecedented accuracy of 10-18 promise innovations in precision spectroscopy and measurement. To harness the full power of optical clocks, we need optical frequency synthesizers (OFSs) to accurately convert the stabilities and accuracies of optical clocks to other desired frequencies. This work demonstrates such an OFS referenced to an ytterbium optical clock. The OFS is based on an optical frequency comb phase-locked to a commercial rubidium microwave clock; in this way most combs can operate robustly. Despite comb frequency instability at 10-11, the synthesis noise and uncertainty reach 6×10-18 (1 s) and 5×10-21, respectively, facilitating frequency synthesis of the best optical clocks. In the OFS, the coherence of the OFS internal oscillator at 1064 nm is accurately transferred to a 578 nm laser for resolving the hertz-level-linewidth ytterbium clock transition (unaffected by megahertz-linewidth comb lines) and faithfully referencing the OFS to an ytterbium optical clock.