Isotopic labelling aldol reactions

When the hydrogen transferred as hydride to the cofactor is retransferred to the same carbon atom in the product, the movement is far more difficult to detect. The conversion of D-glucose 6-phosphate (58) into lL-mt/o-inositol 1-phosphate (61) occurs by cyclization of the carbon skeleton, with formation of a new bond between C-l and C-6. When each carbon atom in turn was specifically labeled with tritium, there was complete retention of tritium, even in the presence of added NADH, although there was an apparent, small isotope-effect with D-glucose-5-t 6-phosphate.19 The mechanism proposed for the cyclization19 was an initial oxidation at C-5 to give NADH and xylo-hexos-5-ulose 6-phosphate (59), followed by an aldol reaction causing cyclization to lL-myo-inosose-2 1-phosphate (60), which is then... 

Reactions in plants are of course catalyzed by enzymes, but the reactions are simply those allowed by organic chemical principles. Familiar processes such as methylation, oxidation, reduction, decarboxylation, aldol condensations, and so on, are frequently involved. In many cases it is difficult to determine the exact sequence of events, but the broad outlines of the biosynthesis of many alkaloids have been elucidated. To take a simple case for illustration of a biosynthetic pathway, the synthesis of coniine in the hemlock tree will be presented. Coniine (3.6) is the poison in hemlock that was used to kill Socrates. As found in Scheme 3.5, the amino acid lysine is the precursor of coniine. The use of radioactive isotopic labels is invaluable in proving such pathways. 

Chiral a-unsubstituted a,)8-unsaturated, isotopically carbon-labeled imides or esters (such as 249 above) needed as starting materials for such applications are best prepared by Horner-Wadsworth-Emmons reaction of e.p. (7 )-or-(5)-A-diethylphosphonoacetyl 4-substituted l,3-oxazolidin-2-ones or bornane-10,2-sultams or of (1R,2S,3R)/ (15,2R,35)-3-[A-phenylsulfonyl-A-(3,5-dimethylphenyl)amino]bornyldiefhylphosphono-acetates (e.g., 252) with aldehydes For purposes of isotopic synthesis, labels could be incorporated either via the haloacetyl group or the aldehyde component, or both, as suggested in Figure 11.87. Entities of the 249-type are also accessible through aldol reaction of the respective homochiral acetyl derivatives 253 with aldehydes, (9-acetylation of the resultant diastereomeric )8-hydroxy intermediates 254 and elimination of HO Ac upon treatment with Both methods avoid the separate preparation of labeled... 

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