Synthesis of Enantiomerically Pure Building Block for Tolyporphins : Synthesis of an Enantiomerically Pure Ring A building block for Tolyporphin and Tolyporphin Derivatives

The enantiomerically pure pyrrolidine diester (Ring A) is a useful building block for the synthesis of chiral tolyporphin and other hydroporphyrin compounds. This was synthesized from enantiomerically pure lactam-lactone. Treatment of optically active aromatic amines with bislactone gave pairs of N-alkylated lactam-lactone diastereomers. These diastereomers were separated by MPL chromatography and debenzylated using ceric (IV) ammonium nitrate (CAN) to yield enantiomerically pure lactam-lactone isomers. The (-)-lactam-lactone enantiomer was treated with methanolic cyanide solution which selectively opened lactone ring to form the cyano lactam. This was further transformed into the cis- and trans-thiocyanolactam isomers. The configurations of these isomers were established by NOE experiment which was confirmed by X-ray measurement and theoretical means(ab initio calculations). Coupling of cis-thiocyanolactam with bromomalonic diester according to the sulphide contraction method gave the enantiomerically pure pyrrolidine diester.