Two members of a new class of calix[6]azacryptands,namely, calix[6]tampo and calix[6]tamb, have been synthesized through an efficient [1 + 1] macrocyclization reaction-reduction sequence. One of them has been obtained in aremarkably high overall yield from the known X
6H
3Me
3. Incomparison to all the other calix[6]azacryptands, they possessunique conformational properties since they present a rigidified cone conformation with a partial filling of the cavityby the methoxy groups. In contrast to calix[6]tampo, the fullyprotonated derivative of calix[6]tamb behaves as a remarkable molecular receptor toward polar neutral guests. NMRstudies have shown that the intracavity binding process isgoverned by a conformational flip of the aromatic walls ofthe calixarene core.