Total synthesis of vitamin

In March 1976, M.A. Wuonola and R.B. Woodward accomplished the conversion of cobyric acid (4) to vitamin B12 (1). The total synthesis of vitamin B12 can thus be claimed, see reference Id, footnote 11, p. 1420. The formal total synthesis of 1 had been accomplished in 1973. 

Sapphyrins were discovered serendipitously by Woodward33 during the course of synthetic studies directed towards the total synthesis of vitamin B, 2. The sapphyrins were the first example of expanded porphyrins in the literature. Due to sapphyrin exhibiting a deep-blue color in the crystalline state and intense green in solution. Woodward coined the expression sapphyrin with reference to the deep-blue color of sapphire stones. 

The fact that pentacarbonyl carbene complexes react with enynes in a chemo-selective and regiospecific way at the alkyne functionality was successfully applied in the total synthesis of vitamins of the Kj and K2 series [58]. Oxidation of the intermediate tricarbonyl(dihydrovitamin K) chromium complexes with silver oxide afforded the desired naphthoquinone-based vitamin K compounds 65. Compared to customary strategies, the benzannulation reaction proved to be superior as it avoids conditions favouring (E)/(Z)-isomerisation within the allylic side chain. The basic representative vitamin K3 (menadione) 66 was synthesised in a straightforward manner from pentacarbonyl carbene complex 1 and propyne (Scheme 38). 

The total synthesis of vitamin Bi2 is a monumental synthetic work published by R. B. Woodward (Harvard) and A. Eschenmoser (Swiss Federal Institute of Technology) ... 

Wick, A. E. Felix, D. Steen, K. Eschenmoser, A. Helv. Chim. Acta 1964, 47, 2425. Albert Eschenmoser (Switzerland, 1925-) is best known for his work on, among many others, the monumental total synthesis of Vitamin B12 with R. B. Woodward in 1973. He now holds appointments at ETH Zurich and Scripps Research Institute, La Jolla. Felix, D. Gschwend-Steen, K. Wick, A. E. Eschenmoser, A. Helv. Chim. Acta 1969, 52, 1030. 

By any standards, the successful total synthesis of vitamin Bi2 which was accomplished by the combined efforts of the Harvard and E.T.H. Zurich groups under Woodward and Eschenmoser, respectively, must rank as a landmark in synthetic organic chemistry. 

A total synthesis of vitamin B12 was announced in 1972, as the result of a collaborative effort between R. B. Woodward (Harvard) and A. Eschenmoser (Zurich). The synthesis was completed after 11 years of effort involving 100 co-workers from 19 countries. A number of important techniques and reactions of synthetic value were developed during the course of this work, including the principle of conservation of orbital symmetry (the Woodward-Hoffman rules, Section 21-10). The biochemical action of vitamin B12 is considered in Chapter 31. 

Initial cyclizadons were effected by the addition of an enamine to an imidate ester, both groups being suitably located by ligand coordination.263 An analogous process can be carried out on a thioimidate but a sulfide is formed and removal of sulfur with consequent ring contraction yields the corrin (100).264 These two complementary routes can be effected with different metal ions, nickel(II), palladium(II) and cobalt(III) in the first route, zinc(II) in the second. Removal of zinc ions easily provides the free corrin macrocycle. These two routes are summarized in Scheme 64. The sulfide contraction route was used in the Eschenmoser-Woodward total synthesis of vitamin Bn-265... 

Vitamin B12, the coenzyme, is sometimes called cyanocobalamine, and is contained in the liver in ppm level. It is comprised of Co2+, porphyrine, cyanide, and porphyrine-side chained nucleoside, and is a complicated complex, as can be seen in Figure 11.1. It is well known that the first total synthesis of vitamin B12 was carried out by Woodward. Vitamin B12 plays a variety of important roles such as rearrangement of C-C bonds (1,2-acyl transfer) and rearrangement of C-N bonds, through radical species. Eq. 11.1 shows a typical acyl-transfer between glutamic acid and... 

Woodward RB (1973) The total synthesis of vitamin B12. Pure Appl Chem 33 145-177... 

Scheme 41. Total synthesis of vitamin E involving a benzannulation.

The key features of a new total synthesis of vitamin E from 2,3,5-trimethylhydroquinone are an enantioselective Wacker cyclisation which generates the chroman ring system with the... 

The preparation of corrins and the total synthesis of vitamin B12 was achieved in the 1970s in the laboratories of Eschenmoser and Woodward as a climax in synthetic chemistry. Indeed, once made accessible by laboratory synthesis, the corrin ring stmcture proved to be accessible on various oxidation levels by an array of ring closme reactions conceived for their possible biosynthetic model... 

Reduction of ArCOOCHi to ArCHi. Saucy and co-workers were able to effect the direct reduction of diester 1 to 2 using this reagent [see also 3, 261). The phenol 2 is an intermediate in a total synthesis of vitamin E. 

Selective hydrolysis of an amide. The analogous reagent -chloro-N-cyclohcxyl-aoetaldonitrone was used in a total synthesis of vitamin Bj 2 to eflect selective hydrolysis of an amide function in the presence of six methyl ester groups. Thu.s treatment of the a-chloronitrone with silver tetrafluoroborate generates the electrophilic cation (I). This... 

The total synthesis of Vitamin B12 provided a sort of proof that nowadays chemists can, in principle, synthesize any (low-molecular-weight) natural product structure, provided they are willing to invest the necessary time... 

This chapter deals with the total synthesis of vitamin E (1) comprising a Pd(II)-catalyzed domino Wacker-Heck reaction as the key step, which allows not only the formation of the chiral chroman framework with an enantioselectivity of 96 % ee but also the simultaneous introduction of part of the side chain. ... 

Tietze and coworkers developed a new total synthesis of vitamin E (1) using a novel enantioselective domino Wacker Heck process as the key step. This allows the formation of the chroman framework 22 with the required i -configuration at the stereogenic center C-2 in 97 % ee with concomitant introduction of part of the vitamin E side chain in 84 % yield. Condensation with (3i )-3,7-dimethyloctanal (21), synthesized from 7 -citronellol (20), followed by reaction with methyl lithium and hydrogenation completed the synthesis. 

As part of the total synthesis of vitamin D3, compound III was converted into IV by a number of stages, two of which involved use of the Wittig reaction. Show how this conversion might have been carried out. 

Enynes of the structural type (57) have been used as key intermediates in the total synthesis of vitamin D. The enyne (57) can be obtained by a simple synthesis based on Pd-catalyzed coupling of the keto-enol triflate (56) and an alkynic compound containing the vitamin D A-ring fragment (Scheme 38). ... 

As a postdoctoral fellow, he worked with R. B. Woodward at Harvard on the total synthesis of vitamin Bj2. X-Ret (See pages( and( ) He is a professor of chemistry at the Universite Louis Pasteur in Strasbourg, France, and at the College de France in Paris. 

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