title: Synthesis of porphobilinogen via a novel ozonide cleavage reaction.
abstract: Porphobilinogen lactam methyl ester (3a) has been prepared in seven steps, and approximately 20-30% overall yield, beginning with furfurylamine (4a).(24) Hydrolysis of 3a following the literature procedure then gave porphobilinogen (1). A key intermediate in our synthesis of 3a is the 7-oxonorbornene derivative 7a, which was derived from 4a utilizing a tandem Johnson ortho ester Claisen rearrangement followed by intramolecular Diels-Alder cyclization (five steps, 55-65%).(24) Interesting steric accelerating effects were observed in this sequence. Conversion of 7a to 3a was then accomplished employing a novel ozonide cleavage/oxidation reaction, which generated tetrahydrofurans 16a, 32, and 33 in the proper oxidation state for direct aminolysis to pyrrole 3a. A mechanism is proposed for the ozonide cleavage/oxidation that accounts for the observed stereoselectivity of this step.
authors.affiliation: Contribution from the Burke Chemical Laboratory, Dartmouth College, Hanover, New Hampshire 03755.
authors.forename: P A
authors.initials: PA
authors.lastname: Jacobi
authors.forename: Y
authors.initials: Y
authors.lastname: Li
mesh_terms: D010126:Ozone / Q000737:chemistry*; D011162:Porphobilinogen / Q000138:chemical synthesis*
chemical_list: D010126:Ozone; D011162:Porphobilinogen