A chemoenzymatic total synthesis of ent-narciclasine

The synthesis of the title compound [(−)-1] has been achieved, for the first time, by reacting the aryl boronic acid ester 4 with the aminoconduritol derivative 6 under Suzuki–Miyaura cross-coupling conditions then subjecting the product phenanthridinone 23 to a global deprotection process using trimethylsilyl bromide. The aromatic building block 4 was prepared in ten steps from piperonal while compound 6 was obtained in nine steps from the enantiomerically pure cis-1,2-dihydrocatechol 7. This last compound is available, in multi-gram quantities, through a whole-cell-mediated biotransformation of bromobenzene using genetically engineered organisms that over-express the responsible enzyme, namely toluene dioxygenase. Since the enantiomer of compound 7 is available by related means, the present work also represents a formal total synthesis of the alkaloid narciclasine [(+)-1]. The single-crystal X-ray analysis of compound 13 is reported.

Subjection of compounds 4 and 6 to Suzuki–Miyaura cross-coupling under microwave irradiation conditions affords the phenanthridinone derivative 23 that upon treatment with trimethylsilyl bromide gives ent-narciclasine [(−)-1].Figure optionsDownload as PowerPoint slide