Anhydride, label attachment with

Hydroxy or hydroxymethyl groups attached to quinolizine substrates normally show the expected reactivity. For instance, compound 109 was linked to histamine receptor antagonists by esterification with succinic anhydride followed by amidification with the antihistaminic drug to give the fluorescently labeled stmcture 110 for in vivo studies of receptor binding (Scheme 13) <2003BML1717>. 

Several syntheses of carbon-14 labeled taxols have been reported. N-3 -[Carbonyl- " C]-taxol 11.1.1 was prepared by coupling a [carbo-nyl- C]-A -benzoyl- 5-lactam with 7-(triethylsilyl)baccatin III (378), while the same group prepared [3 - " C]-taxol 11.1.2 by using a / -lactam prepared from carbonyl- " C-benzaldehyde (379). [3 - " C]-Docetaxel 11.1.3 was prepared by attachment of a labeled cinnamoyl side chain to 7,10-ditroc-10-deacetylbaccatin III, followed by hydroxyamination of the side chain (380). A slightly different approach was used to prepare [2, 3 - " C2]taxol, in that the required doubly labeled /3-lactam synthon was prepared using a doubly labeled Oppolzer s bromoacylbomanesul-tam intermediate (381). 7-([carbonyl- C]-acetyl)taxol was prepared by simple acylation of 2 -(triethylsilyl)taxol with [carbonyl--acetic anhydride and deprotection (382). The taxol analog PNU-105298 (4.1.3.12) was also prepared in both deuterium and carbon-14 labeled forms in both cases the label was placed on the side chain (383). 

As shown in Scheme 12.71, and as affirmed by labeling experiments, an amino acid (shown using phenylalanine [Phe, F] as an example in the scheme) to be added to the growing peptide (protein) chain is activated for reaction by attachment at the carboxylate to adenosine triphosphate (ATP) to make an anhydride of the amino acid with adenosine monophosphate (and the loss of inorganic phosphate). Then, in the next step, the activated amino acid is esterified by the C-2 or the C-3 hydroxyl of a ribosyl unit of AMP, which is attached via phosphate at the 5 carbon to the aminoacyl transfer end of tRNA. If attachment is to C-2, rearrangement to C-3 follows and the aminoacyl-tRNA is activated and ready to be added to the growing peptide chain at the synthesis site on the ribosome. 

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