Simple modular reaction schemes that allow access to any isotopomer of protected serine and homoserine have been worked out. These systems could be simply converted into cysteine, selenocysteine, homocysteine, homoselenocysteine, the essential amino acid methionine, and selenomethionine by Mitsunobu chemistry. These sulfur‐ and selenium‐containing amino acids fulfil many essential roles in the living organism. In addition, homoserine could be converted in a few steps into optically active L‐vinylglycine. As well as the stable isotopes 13C, 15N, 17O, and 18O, the radioactive isotopes of sulfur, selenium and carbon can also be easily introduced in a site‐directed fashion. In view of the wide scope of the Mitsunobu reaction, we feel that many more important systems with the carbon skeleton of serine and homoserine should be preparable through this basic chemistry in any site‐directed isotopically labeled form. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

In this paper a chemo‐enzymatic method has been developed that gives access to any isotopomer of the essential amino acids isoleucine and valine. The method gives the correct introduction of the second chiral center in (2S,3S)‐isoleucine and allows for discrimination between the two prochiral methyl groups in valine as shown by the preparation of (2S,3S)‐[4‐13C] valine. For the preparation of (2S)‐leucine in any isotopomeric form, the O’Donnell method to prepare optically active amino acids has been used. The protected glycine scaffold used in this method has been prepared by a strategy that allows access to any isotopomeric form. The preparation of [5‐13C]‐(2S,4R)‐leucine shows that the O’Donnell method in combination with the Evans method to obtain chiral 2‐methylpropyl iodide leads to a good discrimination between the two prochiral methyl groups. The O’Donnell strategy for the preparation of α‐amino acids is preferred over other methods since the reaction conditions are mild, the chiral auxiliary can be easily recovered and the optically active product can be easily separated. For the preparation of isotopically enriched valine and isoleucine the O’Donnell method is not suitable, because the alkyl substituents involved have a secondary halide substituent which is sterically too hindered to give an effective reaction with the protected glycine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Keywords: Diphenyl phosphonate reagents / Visual analogues / Stereo isomeric synthesis / Synthetic methods / Isomers 5-(2Ј,6Ј,6Ј-Trimethyl-1Ј-cyclohexen-1Ј-yl)-4-penten-2-yn-1-al has been prepared in a one-pot process starting from β-ionone in almost quantitative yield. Using 1,4-nucleophilic addition reactions, the corresponding 9-Cl, 9-Br, 9-I β-ionylideneacetaldehyde systems could be obtained in one step in quantitative yield as a mixture of (9Z) and (all-E) isomers. Even the corresponding fluoro derivative could be obtained in good yield as (9Z) and (all-E) isomers. In the case of a double bond having a halogen substituent, the IUPAC rules have the (E) nomenclature for a cis double bond and the (Z) for a trans double bond. Simple column chromatography gave the pure (9Z) and (all-E) form. Optimizing the Wadsworth−Emmons coupling gave the corresponding (all-E)-and (9Z)-retinonitriles in quantitative yield. Subsequent DIBAL-H reduction gave the corresponding retinals. For the preparation of the (11Z) isomers essential to vision, we found that Wadsworth−Emmons reactions with the diphenyl phosphonate group gave retinonitriles in quantitative yield, where the newly formed double bond is predominantly the