A possible synthetic route to vitamin B12 , proposed by J. W. Cornforth, is discussed in the Introduction, which also briefly gives the present status of other synthetic routes to corrins and to vitamin B12 In Cornforth's approach, precursors of ring A and ring D of vitamin B12 are to be linked together directly by an adaptation of a bromo-nitro coupling reaction and the work described in Chapters 1, 2, 3 and 4 deals with attempts to achieve this coupling and related work. A new synthetic route to Hagemann's ester (4-carbethoxy-3 -methyl- cyclohex-2-ene-1-one), which makes available the t-butyl ester as well as the methyl and ethyl ester in improved yield, has been discovered and is discussed in Chapter 1 with some mechanistic detail. The t-butyl ester adds nitroethane (as do the other esters) in the presence of a Triton base to give a nitro -ester which can be readily hydrolysed to the nitro –acid. The nitro-ester, derived by addition of nitro ethane to ethyl-Hagemann's ester, is shown (Chapter 2) to consist of the two epimers of trans-4-carbethoxy- 3 (methyl, 2-nitroethyl)-cyclohexanone by a degradative sequence involving a Nef reaction followed by a hypobromite oxidation. The product is then related to the known trans-4-carbomethoxy-3 (methyl, carbomethoxy)- cyclohexanone. The nitro-adducts thus have the correct ring stereochemistry for further development into vitamin B12 , This degradation can also be used for correlation of the enantiomers of the nitro acid after resolution. The nitro-ethyl ester epimers are converted (Chapter 3) into a single bromo-isomer (trans-4-carbethoxy-3 (methyl, 2,2-bromonitro-ethyl)- cyclohexanone and a coupling reaction with a primary nitro-anion is described, The failure of this reaction to give coupled products leads to the protection of the ketone in the nitro -ethyl ester with an ethylene -ketal followed by conversion into a single bromo -isomer , This compound also failed in the coupling reaction. The production of a single bromo-isomer from two epimers has important implications and hence a series of acid quenching of nitroanions is studied. These show remarkable stereo selectivity and several novel mechanistic features are discussed. The stereochemistry of a possible ring D precursor had not been determined in its entirety and Chapter 4 shows how the problems can be resolved although only the initial stages have been achieved.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:594896 |
| Date | January 1970 |
| Creators | Begbie, Alexander Lovelace |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/72935/ |
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