Synthesis of 1,2-dioxetanes

A process for producing a 1,2-dioxetane compound having the formula:

• ##STR52## in which T is a spiro-bonded stabilizing group that prevents the dioxetane compound from decomposing before the bond between Y and Z is intentionally cleaved, Y is an aromatic, light-emitting fluorophore-forming fluorescent chromophore group capable of absorbing energy to form an excited energy state from which it emits optically detectable energy to return to its original energy state, Z is hydrogen, a chemically cleavable group or an enzyme-cleavable group, and R is a C.sub.1 -C.sub.20 unbranched or branched, substituted or unsubstituted, saturated or unsaturated alkyl group;
• a heteroalkyl group or aralkyl group;
• a substituted or unsubstituted polynuclear or heteropolynuclear aralkyl group;
• a saturated or unsaturated cycloalkyl group;
• an N, O or S heteroatom-containing group;
• or an enzyme-cleavable group, with one or more of T, Y, Z or R being substituted with a group that enhances the water solubility of the 1,2-dioxetane or unsubstituted with such a group, which comprises:
• reacting an aldehyde having the formula:
• T--CHO
• with an aromatic organolithium compound having the formulae:
• R' O Y Li
• or XMgYOR' and X is halogen wherein R' is a substituent as defined for R hereinabove, and oxidizing the thus-obtained reaction to form the corresponding ketone having the formula:
• ##STR53## reacting the ketone with base plus an R-ylating agent to form the corresponding enol ether having the formula:
• ##STR54## selectively deetherifying the enol ether to form the corresponding monohydroxy enol ether having the formula:
• ##STR55## converting the hydroxy group in the monohydroxy enol ether to a Z group to form the corresponding enol ether having the formula:
• ##STR56## and oxygenating the T.dbd.C double bond ether to give the corresponding 1,2-dioxetane compound.

A process for producing a 1,2-dioxetane compound having the formula:

• ##STR68## wherein T is a polycycloalkylidene group, R is a C.sub.1 -C.sub.20 unbranched or branched, substituted or unsubstituted, saturated or unsaturated alkyl group;
• a heteroalkyl group or aralkyl group;
• a substituted or unsubstituted polynuclear or heteropolynuclear aralkyl group;
• a saturated or unsaturated cycloalkyl group;
• an N, O or S heteroatom-containing group;
• or an enzyme-cleavable group;
• Y is an aromatic, light-emitting fluorophore-forming fluorescent chromophore group capable of absorbing energy to form an excited energy state from which it emits optically detectable energy to return to its original energy state, and Z is an O-glycosidically linked sugar molecule, which comprises reacting a monohydroxy enol ether having the formula:
• ##STR69## with a tetra-O-acyl-D-hexopyranosyl halide to give a compound having the formula:
• ##STR70## hydrolyzing the O-tetraacetate groups in the D-hexopyranoside tetraacetate to give a compound having the formula:
• ##STR71## and oxygenating the double bond to give the corresponding 1,2-dioxetane compound.