Synthesis of Porphobilinogen via a Novel Ozonide Cleavage Reaction

• Published in: Journal of the American Chemical Society Vol. 123; no. 38; pp. 9307 - 9312
• Main Authors: Jacobi, Peter A, Li, Yongkai
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 26.09.2001; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Ozone - chemistry; Physical Sciences; Porphobilinogen - chemical synthesis; Science & Technology; REAGENT; BIOSYNTHESIS; DIELS-ALDER REACTION; CHEMISTRY; CONVENIENT; OXIDATIVE CLEAVAGE; CLAISEN REARRANGEMENT; CARBOXYLIC-ACIDS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja016303q

Porphobilinogen lactam methyl ester (3a) has been prepared in seven steps, and ∼20−30% overall yield, beginning with furfurylamine (4a). 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%). 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.