2012- 21st Annual NC State Undergraduate Research Symposium

Session Time : 4/10/12 10:30 AM - 4/10/12 11:45 AM

Content Area : Chemistry

Poster Appointment: NONE

Student Presenters :
Richard McAlister Deans Chemistry

Mentors and/or Co-Authors :
Jonathan Lindsey Chemistry

Abstract Title : Facile Synthesis of a Close Analogue of Vitamin B12

Abstract :
Vitamin B₁₂ is the most architecturally complex molecule employed in enzymatic catalysis in living systems. Understanding the catalytic properties of such cofactors requires access to a range of synthetic analogues for examination in diverse model reactions. However, the complexity of vitamin B₁₂ has stymied this time-honored approach. The molecular skeleton of vitamin B₁₂ is a corrin, which differs from the well-known porphyrins (e.g., heme) in (i) the high degree of saturation, and (ii) the contraction of the ring by one carbon. Fully unsaturated corrin analogues (octadehydrocorrins) have been studied extensively, yet more reduced analogues have remained synthetically inaccessible. We found previously that self-condensation of a dihydrodipyrrin-acetal affords a B,D-tetradehydrocorrin (TDC-T⁷T¹⁷) in good yield. Tetradehydrocorrin macrocycles occupy a reduction level halfway between that of octadehydrocorrins and corrins, and have been little studied despite their close similarity to corrins. However, the reactive 1-acetal moiety of TDC-T⁷T¹⁷ was an Achilles heel, enabling rearrangement of the macrocycle to the analogous bacteriochlorin under acidic conditions. Here, the reaction of two distinct dihydrodipyrrins in the presence of Ga(OTf)₃ afforded (29% yield) a novel B,D-tetradehydrocorrin (TDC-EP⁷T¹⁷), which lacks the reactive 1-acetal moiety and is stable to acid. Furthermore, this directed route enabled the installation of distinct substituents on opposite sides of the macrocycle. We are presently examining the metalation of TDC-EP⁷T¹⁷ with cobalt and nickel to achieve further structural similarity with vitamin B₁₂. The facile access to stable, synthetically tailored metallo-B,D-tetradehydrocorrins should open the door to diverse fundamental studies related to vitamin B₁₂.