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The total synthesis of Vitamin B12 was accomplished by the collaborating research groups of Robert Burns Woodward at Harvard and Albert Eschenmoser at ETH in 1972. It is considered a classic in the field of total synthesis of natural products. Work on the synthesis started 1960 at ETH, and in 1961 at Harvard, it was collaboratively pursued after 1965, and required the effort of no less than 91 post-doctoral fellows (mostly at Harvard) and 12 Ph.D. students (at ETH) from 19 different nations. There are two variants of this synthesis, concomitantly accomplished in 1972. These two syntheses are intricately intertwined chemically, yet they basically differ in their overall strategy of creating the macrocyclic corrin ligand system of the vitamin molecule. The variant collaboratively pursued and finished at Harvard closes the macrocyclic corrin ring between rings A and B (the "A/B variant"), while the synthesis accomplished at ETH achieves the corrin ring closure between rings A and D by a photochemical process (the "A/D variant"). Woodward reported on the A/B variant in lectures published in 1968, 〔 1971,〔 and 1973,〔 culminating in the announcement of the "Total Synthesis of Vitamin B12" in his lecture at the IUPAC Conference in New Delhi, July 1972.〔 Eschenmoser discussed the ETH-contributions to the A/B variant in his Centenary Lecture, published in 1970,〔 and presented the approach to the photochemical A/D variant of the B12 synthesis at the 23rd IUPAC Congress in Boston, published in 1971.〔 A full report on the photochemical variant is given in a Science article 〔 of 1977 which is an extended English translation of a 1974 Naturwissenschaften article,〔 based on a lecture given by Eschenmoser at the Chemical Society of Zürich. The two variants of the chemical synthesis of vitamin B12 have been reviewed by R.V. Stevens and Nicolaou & Sorensen,〔 and discussed in more or less detail in more than 40 other publications. The account given here is based on the three published B12 lectures of Woodward 〔〔〔 and, therefore, deals with the Harvard-ETH A/B variant only. The X-ray crystal structure of Vitamin B12 had been determined by Dorothy Hodgkin (Oxford University) in collaboration with Kenneth N. Trueblood (UCLA) and John G. White (Princeton University) in 1956. According to Woodward, an observation made during the synthesis of the Harvard A-D component played an essential role in the conception of the Woodward–Hoffmann rules for orbital symmetry control of organic reactions formulated in 1965. ==The molecule== The core of the molecule vitamin B12 (cobalamin) is a corrin structure (depicted in red) with at its center a cobalt ion. Several vitamins exist with different cobalt ligands but the total synthesis concerned the one with a cyano ligand called cyanocobalamin. The corrin rim is lined with methyl groups (8) and lined with amide groups (6) linked through C1 and C2 spacers. A seventh amide group is N-alkylated by a large tail consisting of an isopropanol group, a phosphate group, a ribose group and a dimethylbenzimidazole group. One of the nitrogen atoms on the imidazole is a fifth nitrogen ligand for the cobalt atom. A total of nine carbon atoms on the corrin frame are chiral, adding another challenge to the synthesis. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Vitamin B12 total synthesis」の詳細全文を読む スポンサード リンク
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