Arnold A. Liebman

A route to tritium labelled 11-methyl prostaglandins

Labelled 11-methyl prostaglandins have been prepared via the catalytic tritium reduction of 11-iodomethyl intermediates. Two examples are reported for the preparation of such 11-iodomethyl precursors in which the desired lower side chain is attached in non-radioactive steps. Subsequent tritium hydrogenolysis of the 11-iodomethyl lactones followed by addition of the delta 5 cis-double bond yielded prostaglandins having specific activities of 10-15 Ci/mmol.

The synthesis of 25-hydroxy-cholecalciferol-23,23,24,24-t4 of high specific activity

Abstract Catalytic tritium reduction of cholest-5-en-23-yne-3β,25-diol diacetate ( VIII ) gave cholest-5-ene-3β,25-diol diacetate- 23 , 23 , 24 , 24 - t 4 ( IX ) having a specific activity of 92 Ci/mmol. Bromination, dehydrobromination and hydrolysis of the labelled material gave cholesta-5,7-diene-3β,25-diol- 23 , 23 , 24 , 24 - t 4 ( XI ) which was photolyzed to the previtamin and then thermally equilibrated to 25-hydroxy-cholecalciferol- 23 , 23 , 24 , 24 - t 4 ( I ).

[25] Affinity labeling of tRNA-binding sites on ribosomes

During the past several years a variety of chemically reactive derivatives of tRNA have been synthesized for use as affinity labels for amino acid-tRNA ligases, ribosomes, and factors involved in protein biosynthesis. Particularly in the study of Escherichia coli ribosomes, progress has been rather rapid. Besides affinity-label derivatives of tRNA, reactive derivatives of oligo- and polynucleotides have been constructed to label the ribosomal site for mRNA binding. Furthermore, a number of small-molecular-weight substances, such as antibiotics and GTP, have been chemically modified to obtain specific reagents for their respective ribosomal binding sites. The field of affinity labeling of ribosomes has been reviewed before with emphasis on various aspects of this problem (Cantor et al. 1974; Pellegrini and Cantor 1977; Zamir 1977; Cooperman 1978; Kuechler 1978). Here we want to concentrate primarily on affinity-labeling studies dealing with the ribosomal binding site for tRNA and on the interaction of tRNA with mRNA. The results will be correlated with the existing data on the structural organization of the ribosome as obtained by electron and immuno-electron microscopy and used to outline the functional domains on the ribosome for different regions of the tRNA. AFFINITY- AND PHOTOAFFINITY-LABEL DERIVATIVES OF tRNA Position of the Affinity-labeling Group Attachment of an affinity-labeling group to aminoacyl-tRNA requires special precautions to insure single-site specificity. In most studies, advantage has been taken of the existence of the single, highly reactive α -amino group on the aminoacyl moiety of tRNA. Thus, affinity reagents have usually been bound via an amide bond with the...

[5] Synthesis of carotenoids specifically labeled with isotopic carbon and tritium

Publisher Summary The chemistry used in the synthesis of carotenoids is extensive and has been periodically reviewed. This chapter discusses the expanding use of chiral reagents and other tools of modern organic synthesis and the increasing use of isotopically labeled carotenoids in a variety of applications. In general, carotenoids that have been specifically labeled at one or more particular positions have been prepared with stable isotope variants, while carotenoids labeled with a radioactive isotope have usually been prepared from a labeled precursor by biosynthesis. Notable exceptions are certain carotenoids labeled with tritium. Partial reduction of an alkyne precursor of these carotenoids with tritium gas produces these labeled materials. Specific labeling is necessary in areas, such as mass spectral rationalizations of carotenoids, in which the use of deuterium enrichment is essential for meaningful interpretation. In addition, methodology has now been developed to prepare carotenoid compounds specifically labeled with isotopic carbon along with tritium.

Selective reduction of a carboxyl group with diborane. Synthesis of specifically carbon-14 labelled D,L-2-Amino-4-(2-aminoethoxy)butanoic acid

Specific labelling of the title compound was achieved through intermediate 3a, methyl 2-(2-phthalimidoethoxy)acetate, derived from methyl bromoacetate-2-14C. Conversion to the corresponding acid (4) was followed with selective diborane reduction which provided 2-(2-phthalimidoethoxy)ethanol-2-14C (5). Treatment with thionyl chloride yielded the chloride 6 which is identical with the intermediate used in the nonlabelled synthesis and reaction with sodium ethyl phthalimidomalonate provided the title compound after hydrolytic work-up.

[6] The preparation of l-ascorbic acid [35S]2-sulfate having a high specific activity

Publisher Summary The preparation of tracer levels of ascorbic acid [35S]2-sulfate generally involves the treatment of a 5,6-acetal of L-ascorbic acid with an amine-sulfur trioxide complex in a polar aprotic solvent. This chapter discusses the preparation of L-ascorbic acid [35S]2-sulfate having a high specific activity. The sulfation of 5,6-O-isopropylidene ascorbic acid (III) can be carried out more efficiently with sulfur trioxide in dimethylformamide. Removal of the 5,6-isopropylidene group is effected by passage of the labeled substrate (IV) through a column of Dowex 50 (H+) ion-exchange resin, a method that minimizes contamination of the product with inorganic sulfate. The resulting ascorbic acid [35S]2-sulfate can be crystallized as the dipotassium salt or as the barium salt; the insolubility of barium sulfate in water makes purification in this latter case much easier.

SELECTIVE REDUCTION OF A CARBOXYL GROUP WITH DIBORANE. SYNTHESIS OF SPECIFICALLY CARBON‐14‐LABELED D,L‐2‐AMINO‐4‐(2‐AMINOETHOXY)BUTANOIC ACID

Specific labelling of the title compound was achieved through intermediate 3a, methyl 2-(2-phthalimidoethoxy)acetate, derived from methyl bromoacetate-2-14C. Conversion to the corresponding acid (4) was followed with selective diborane reduction which provided 2-(2-phthalimidoethoxy)ethanol-2-14C (5). Treatment with thionyl chloride yielded the chloride 6 which is identical with the intermediate used in the nonlabelled synthesis and reaction with sodium ethyl phthalimidomalonate provided the title compound after hydrolytic work-up.