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Treatment of various phenylsulfoximines with nBuLi (1 equiv.) at -78°C in THF resulted in single ortho-lithiations and gave the corresponding o-lithiosulfoximines. According to NMR spectroscopy, the o-lithiosulfoximines are generally stable at 0°C. The o-lithiosulfoximines were efficiently trapped through deuteration, alkylation, silylation, and phosphanylation. Treatment of cyclic phenylsulfoximines also containing H atoms at their α-positions with nBuLi (1 equiv.) at -78°C furnished the o-lithiosulfoximines with high selectivity, whereas similar treatment at -50°C to room temperature yielded the corresponding α-lithiosulfoximines. At elevated temperatures, o-lithiosulfoximines also possessing α-H atoms underwent quantitative o,α-transmetalation to afford the corresponding α-lithiosulfoximines. Treatment of α,α-disubstituted cyclic and α,α,α-trisubstituted acyclic phenylsulf-

A new series of 2,3-diaryl-4/5-hydroxy-cyclopent-2-en-1-one analogues replacing the cis double bond of combretastatin A-4 (CA-4) by 4/5-hydroxy cyclopentenone moieties was designed and synthesized. The analogues displayed potent cytotoxic activity (IC50<1 microg/mL) against a panel of human cancer cell lines and endothelial cells. The most potent analogues 11 and 42 belonging to the 5-hydroxy cyclopentenone class were further evaluated for their mechanism of action. Both of the analogues led to cell cycle arrest at G2/M phase and induced apoptosis in endothelial cells. Antitubulin property of 42 was superior to 11 and comparable to CA-4. The compound 42 had better aqueous solubility, metabolic stability, and pharmacokinetic profile than CA-4 and also demonstrated significant tumor regression in the human colon xenograft model. Our data suggests that cis-restricted analogues of CA-4 are a new class of molecules that have the potential to be developed as novel agents for the treatment of cancer.