The regiocontrolled syntheses of four chiral C1- or C3-symmetrical tribenzotriquinacene (TBTQ) derivatives bearing methoxy or hydroxy groups at the peripheral positions [(2,6-(OMe)2, (±)-18 and (±)-20; 2,6-(OH)2, (±)-19; and 2,6,10-(OMe)3, (±)-21] by two different synthesis protocols are reported. Compounds (±)-19, (±)-20, and (±)-21 and two (already-known) monosubstituted C1-symmetrical TBTQ analogues [2-OH (±)-23 and 2-OMe (±)-24] were readily resolved by chiral HPLC, and their absolute configurations were determined by X-ray crystallography and/or circular dichroism (CD) studies. Optical resolution of three closely related TBTQ derivatives [2,6-(OMe)2, (±)-18; 2-OMe, (±)-22; and 2-OH, (±)-25] containing the same peripheral substituents but other bridgehead residues failed. Enantiopure TBTQ derivatives of this sort are considered promising structural motifs toward the construction of molecular squares and cubes.