Five cyclitol analogues of SL0101 with variable substitution at the C-4' position (i.e., OH, Cl, F, H, OMe) were synthesized. The series of analogues were evaluated for their ability to inhibit p90 ribosomal S6 kinase (RSK) activity. The study demonstrated the importance of the B-ring C-4' hydroxy group for RSK1/2 inhibition.