Total Synthesis of Cobyric Acid: Historical Development and Recent Synthetic Innovations

Abstract

The total synthesis of vitamin B12 and its precursor, cobyric acid, has been one of the most demanding and elusive goals in synthetic organic chemistry for over thirty years. This review outlines the historical development leading to the first and so far only total synthesis, by Woodward and Eschenmoser, and gives an account of later contributions from the groups of R. V. Stevens, P. A. Jacobi, and J. Mulzer. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Analysis of vitamin B12 in foods ‐ development and application of stable isotope dilution assays for naturally occurring cobalamins

“…(namely CNCbl), straightforward incorporation between the corrin ring and the nucleotide-containing lower ligand has been accomplished since 1960 [116] . Until now, synthetic chemists are still working on alternative routes for a more efficient synthesis of the cobyric acid but so far no other total synthesis has been successfully achieved [117] .…”

Analysis of vitamin B12 in foods ‐ development and application of stable isotope dilution assays for naturally occurring cobalamins

“…(namely CNCbl), straightforward incorporation between the corrin ring and the nucleotide-containing lower ligand has been accomplished since 1960 [116] . Until now, synthetic chemists are still working on alternative routes for a more efficient synthesis of the cobyric acid but so far no other total synthesis has been successfully achieved [117] .…”

Applications of the Wittig–Still Rearrangement in Organic Synthesis

“…Thus the classic Woodward–Eschenmoser total synthesis still remains the only completed one. Efforts of Mulzer and others are summarized in a review …”

Anwendungen der Wittig‐Still‐Umlagerung in der organischen Synthese

“…Somit bleibt die klassische Woodward‐Eschenmoser‐Totalsynthese die einzig vollendete Synthese. Die Synthesestudien von Mulzer und anderen wurden in einem Übersichtsartikel zusammengefasst …”

Analysis of vitamin B12 in foods ‐ development and application of stable isotope dilution assays for naturally occurring cobalamins

“…(namely CNCbl), straightforward incorporation between the corrin ring and the nucleotide-containing lower ligand has been accomplished since 1960 [116] . Until now, synthetic chemists are still working on alternative routes for a more efficient synthesis of the cobyric acid but so far no other total synthesis has been successfully achieved [117] .…”

Applications of the Wittig–Still Rearrangement in Organic Synthesis

“…Thus the classic Woodward–Eschenmoser total synthesis still remains the only completed one. Efforts of Mulzer and others are summarized in a review …”

Anwendungen der Wittig‐Still‐Umlagerung in der organischen Synthese

“…Somit bleibt die klassische Woodward‐Eschenmoser‐Totalsynthese die einzig vollendete Synthese. Die Synthesestudien von Mulzer und anderen wurden in einem Übersichtsartikel zusammengefasst …”

Analysis of vitamin B12 in foods ‐ development and application of stable isotope dilution assays for naturally occurring cobalamins

“…(namely CNCbl), straightforward incorporation between the corrin ring and the nucleotide-containing lower ligand has been accomplished since 1960 [116] . Until now, synthetic chemists are still working on alternative routes for a more efficient synthesis of the cobyric acid but so far no other total synthesis has been successfully achieved [117] .…”

Applications of the Wittig–Still Rearrangement in Organic Synthesis

“…Thus the classic Woodward–Eschenmoser total synthesis still remains the only completed one. Efforts of Mulzer and others are summarized in a review …”

Anwendungen der Wittig‐Still‐Umlagerung in der organischen Synthese

“…Somit bleibt die klassische Woodward‐Eschenmoser‐Totalsynthese die einzig vollendete Synthese. Die Synthesestudien von Mulzer und anderen wurden in einem Übersichtsartikel zusammengefasst …”