Formyl transfer

The transfer of 1-carbon units at this oxidation level originally was thought to involve two derivatives of H4-folate, 10-formyl-H4-folate and 5,10-methenyl-H4-folate which acted as cofactors for the two transformylases in de novo purine biosynthesis [67-69]. However, recent work has shown that the glycinamide ribonucleotide transformylase (GAR TFase) from E. coli as well as from avian liver utilize 10-formyl-H4-folate as the actual cofactor [70,71]. The preference for 10-for-myl-H 4-folate was masked by the presence of the opposite, unreactive diastereomer (R at C-6 in H4-folate) which is an excellent competitive inhibitor of the enzyme. The apparent reactivity of the 5,10-methenyl-H4-folate in the same assay arose because of a contaminating cyclohydrolase activity capable of selectively hydrolyzing it to the correct diastereomer of 10-formyl-H4-folate. 

TFase and vice versa. Furthermore, the transfer of the lO-formyl group does not appear to proceed through a dehydration-hydration sequence involving an amine function on either enzyme since 0 is not exchanged into the 1-carbon unit during transfer [73]. 

A bifunctional protein containing the dehydrogenase and cyclohydrolase activities has been purified from E. coli. Whether these activities reside at a single or multiple site is not yet resolved unequivocally. In the case of the trifunctional protein from porcine liver, probes employing tryptic digests and assays for intermediate species, e.g. the level of the intermediate 5,10-methenyl-H4-folate, implicate a proximal or single dehydrogenase-cyclohydrolase site [78-80]. 

Note that the hydrolytic ring opening of 5,10-methenyl-H4-folate proceeds to the N-10 formyl isomer which is the product of kinetic control. In this case (recall 

10-methylene) the higher basicity of N-5 relative to N-10 insures an increased degree of protonation, so that it is the preferred leaving group in the decomposition of any tetrahedral intermediate arising from nucleophilic addition to C-11 [81]. 

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FORMYL TRANSFER TO GRIGNARD REAGENTS 3-PHENYLPROPIONALDEHYDE (Benzenepropanal)... 

M. E. Jung and S. W. T. Choe, Stereospecific intramolecular formyl transfer via radical cyclization-fragmentation—preparation of alkyl 2-deoxy-2-ot-formylglucopyranosides and similar compounds, Tetrahedron Lett. 34 6247 (1993). 

A unique reaction of formyl complexes is formyl transfer," in which the formyl ligand undergoes apparent migration from one metal to another. This transformation was first observed with the manganese formyl 12, as shown in Eq. (19) (35, 47). However, 12 is unstable at room temperature and cannot be separated from trialkylborane by-product. Therefore, it is again important to establish that this type of reaction proceeds with pure formyl complexes. 

Two formyl transfer" reactions of isolated formyl complexes are shown in Eqs. (20) (37, 42) and (21) (37, 38, 42, 47, 66). Control experiments indicate that these reactions do not involve metal hydride intermediates (formed via decarbonylation). Straightforward intermolecular H transfer (rather than formyl ligand transfer) is believed to be taking place. 

Formyl transfers" involving neutral formyl complexes, such as shown in Eq. (22), have recently been reported (68). By precipitation of the metal carbonyl cation by-product, quite pure solutions of kinetically labile neutral formyl complexes may be obtained. 

When the reaction was conducted in benzene with 1.0-1.5 equiv. of Bu3SnH and 0.01-0.5 equiv. of AIBN under reflux, formyl-transfer product isopropyl 3,4,6-tri-0-acetyl-2-deoxy-2-C-formyl-o -D-glucopyranoside 162a was isolated in 40% yield. The bicyclic alcohols... 

Metal/halogen exchange with 2,5-dibromopyridine leads exclusively and efficiently to 2-bromo-5-lithiopyridine in a thermodynamically controlled process it has been suggested that the 2-pyridyl anion is destabilised by electrostatic repulsion between nitrogen lone pair and the adjacent anion " this same factor is probably important in the greater difficulty found in generating 2,3-pyridyne (see section 5.3.2). The example below illustrates the use of the Weinreb amide of formic acid as a formyl-transfer reagent. ... 

Chapter I. Methyl, hydroxyl and formyl transfer by G. L. Cantoni (Bethesda, Md.) Chapter II. Transaldolase and transketolase by B. L. Horecker (New York, N.Y.) Chapter III. Transfer of acyl groups (CoA structure, function) by R.Vagelos (Bethesda,... 

A formyl group can be transferred to an alkene [29]. When a mixture of aldehyde 52 and benzonorbornadiene was treated with a rhodium catalyst, a mixture of alkene 53 and aldehyde 54 was produced (Scheme 7.20). The formyl-transfer reaction proceeds through retro-hydroformylation of aldehyde 52 followed by hydroformylation of benzonorbornadiene. 

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