3-(3-Pyrrolyl)thiopyrrolidones as Precursors of Benzodipyrroles. Synthesis of Intermediates and Analogues Related to the Phosphodiesterase Inhibitors PDE I and PDE II and Antitumor Antibiotic CC-1065

Article abstract of DOI:10.1021/jo00240a008

The 4-lithio derivative of ethyl 5-(3-methylisoxazol-5-yl)pyrrole-2-carboxylate adds to the 3-position of 1-allylpyrrolidine-2,3-dione to give ethyl 4-(1-allyl-3-hydroxy-2-oxopyrrolidin-3-yl)-5-(3-methylisoxazol-5-yl)-pyrrole-2-carboxylate in 53percent yield.This adduct has been converted to ethyl 4-(1-allyl-2-thioxopyrrolidin-3-yl)-5-(1,3-dioxobutyl)pyrrole-2-carboxylate.This thiolactam is cyclized to ethyl 5-acetyl-6-allyl-4-hydroxy-3,6,7,8-tetrahydrobenzo<1,2-b:4,3-b'>dipyrrole-2-carboxylate by reaction with methyl iodide at 80 deg C.The cyclization product has been converted to methyl 5-acetyl-4-methoxy-3,6,7,8-tetrahydrobenzo<1,2-b:4,3-b'>dipyrrole-2-carboxylate, an intermediate in synthesis of PDE II methyl ester (Boger and Coleman, 1986).The thiolactam has also been converted to ethyl 7-allyl-4-oxo-3,4,5,6,7,8-hexahydrothiepino<2,3-b:5,4-b'>dipyrrole-2-carboxylate.This thiepinone undergos ring contraction to ethyl 6-allyl-4-hydroxy-3,6-dihydrobenzo<1,2-b:4,3-b'>dipyrrole-2-carboxylate.This compound has been converted to ethyl 6-acetyl-4-methoxy-3,6,7,8-tetrahydrobenzo<1,2-b:4,3-b'>dipyrrole-2-carboxylate, the 5-deoxy analogue of PDE II ethyl ester.