An optimized fermentation process is described for the carbon‐14 labelling of rapamycin. It is characterized by good reproducibility, high radiochemical purity and excellent yields. L‐[14C2]Pipecolic acid and (1R,3R,4R)‐3,4‐dihydroxyl[1,7‐14C2]cyclohexane carboxylic acid ([14C2]DHCCA) synthesized in an effective stereoselective approach proved to be highly suitable precursors for this purpose. In a final step [14C4]rapamycin was converted by selective C(40)‐O‐alkylation to [14C4]NVP RAD001, a highly interesting immunosuppressant. Copyright © 1999 John Wiley & Sons, Ltd.

Addition of [3-14 C]D/L-tryptophan to the fermentation broth allowed radiofermentative labeling of staurosporine. The approach providing [4c,7a-14 C 2 ]staurosporine in a range from 700 to 1300 MBq/mmol was straightforward and easy to handle as well as safe from a radioprotection point of view. The presented example underlines that close cooperation of microbiologists and radiochemists is a requisite for the success of this approach.

As a highly specific and non peptide AT1‐antagonist Valsartan 2 is marketed under the tradename DIOVAN™ for effective treatment of hypertension. This paper describes the synthesis of C‐14 labelled Valsartan 2, which incorporates two C‐14 isotopes in the valine‐moiety. Reaction of (−)‐bromo‐[1,2‐14C]acetyl bornane‐10.2‐sultam 8a ((−)‐[14C2]BABS) with benzophenone imine gave (−)‐diphenyl‐methylene[1,2‐14C2]glycinyl bornane‐10.2‐sultam 9 ((−)‐[14C2]DPMGBS), which was alkylated with 2‐iodopropane to build‐up the valine structure 10. Initially the resulting sultam‐protected valine 11 was treated with the benzyl bromide 12 to produce the precursor 13. However, under conditions routinely used for sultam‐cleavage deprotection resulted in the racemization of the amino acid. Successful cleavage was accomplished via N‐Boc‐protection of 11 followed by hydrolytic cleavage of the auxiliary and esterification to give the L‐[14C2]valine benzyl ester 18. Finally [14C2]Valsartan 2 was synthesised in a 10 step synthesis in an overall radiochemical yield of 10 % relative to the (−)‐[1,2‐14C]BABS 8a employed. Copyright © 2000 John Wiley & Sons, Ltd.

No abstract

Use of Microwaves in Organic Synthesis: Application in the Synthesis of Isotopically Labelled Compounds Preparation of Tritium‐Labelled BIIL 260 with High Specific Radioactivity Synthesis of [3H]‐, [14C]‐ and [13C,2H]‐labelled Org 12962 Derivatives Labeling of BAY 58‐2667, an Activator of sGC Preparation and Use of [14C]N,N′‐Carbonylditriazole in the Labelling of Urea Derivatives Efficient Carbon‐14 Labeling of 2‐(3‐Hydroxypropyl)‐1H‐benzimidazole Synthesis of Some 14C‐Labelled Fungicides C‐14 Labelling of NVP‐ABE651 and NVP‐ABE697 Synthesis of Carbon‐13,14 Isotopomers of a Novel 4‐Substituted‐2‐Carboxy Tetrahydroquinoline [14C]CH2N2: A Suitable Precursor for the Preparation of 14C‐Labelled Anthracyclines Preparative HPLC: a Useful Approach to Speed‐up the Purification of Labelled Compounds. Use of Stable Isotopes for the Biosynthesis and Biodegradation of Fosfomycin Metalloradiopharmaceuticals for Nuclear Medicine Strategic outlook: Future Methods in DMPK and subsequent requirements for isotopically labelled compounds Isotopic Imaging of Glass‐based cDNA Microarray Hybridization New Developments in Radiation Measuring Technique