An approach to cytochalasan synthesis: macrolide formation by an intramolecular Diels-Alder reaction. X-Ray structure of methyl (1RS, 2SR, 5RS, 6RS)-2,5-dimethyl-1-hydroxy-6-[(1RS)-1-hydroxy-2-phenylethyl]cyclohex-3-ene-1-carboxylate

Abstract

When heated in toluene under reflux, under high dilution conditions, trans,trans-hexadeca-12,14-dienoyloxymaleic anhydride (4) cyclized via an intramolecular Diels-Alder reaction to give the macrocyclic lactone (5) in 27% yield together with 5% of a regioisomer (23). (1RS, 2SR, 5RS, 6RS)-2,5-Dimethyl-1-octanoyloxycyclohex-3-ene-1,6-dicarboxylic acid anhydride (11) was converted into methyl (1RS, 2SR, 5RS, 6RS)-2,5-dimethyl-1-octanoyloxy-6-benzylcarbonylcyclohex-3-ene-1-carboxylate (33), but selective reduction of this ketone was unsuccessful. The structure of one of the reduction products, methyl (1RS, 2SR, 5RS, 6RS)-2,5-dimethyl-1-hydroxy-6-[(1RS)-1-hydroxy-2-phenylethyl] cyclohex-3-ene-1-carboxylate (35) was confirmed by an X-ray structure determination.