The synthesis of two potential cross-linking reagents: 2,2'-sulfonylbis(3-(benzylamino)-(E,E)-N-(2-oxoethyl)propenamide) (SBBOP) and 2,2'-sulfonyl(3-(benzylamino)-(E,E)-N-(2-chloroethyl)propenamide) (SBBCP)

The synthesis of the 2-oxoethyl- and 2-chloroethyl derivatives of 2,2'-sulfonylbis(3-(benzylamino)-(E,E)-N-propenamides) (SBBOP and SBBCP) provides improved hemoglobin cross-linking reagents. The two are prepared in 14.7% and 34% respective yields from dimethyl 2,2'-sulfonyldiacetate by a six-step convergent process. An alternative four-step route from the same substrate produces SBBCP in 65% yield. Subsequent X-ray studies show the SBBOP and SBBCP have a tether distance of 9.18 angstroms, enough to place them within hemoglobin's DPG pocket for cross-linking.