- A step-wise synthetic approach is necessary to access γ-conjugates of folate: Folate-conjugated prodigiosenes
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Despite the vast literature that describes reacting folic acid with a pharmacophore, this route is ineffective in providing the correct regioisomer of the resulting conjugate. We herein present a step-wise route to the preparation of nine folate conjugate
- Figliola, Carlotta,Marchal, Estelle,Groves, Brandon R.,Thompson, Alison
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p. 14078 - 14092
(2019/05/21)
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- Synthesis and analysis of bacterial folate metabolism intermediates and antifolates
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The mechanism of action of para-aminosalicylic acid (PAS), a drug used to treat drug-resistant tuberculosis (TB), has been confirmed through the first synthesis and biochemical characterization of its active metabolite 7. The synthesis features the coupling of N2-acetyl-6-formylpterin obtained from the degradation of folic acid and appropriately functionalized arylamines to form Schiff bases. The sequential chemoselective reduction of the imine and pterin ring led to the formation of dihydrofolate analogue 7 and two other dihydropteroate species.
- Dawadi, Surendra,Kordus, Shannon L.,Baughn, Anthony D.,Aldrich, Courtney C.
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supporting information
p. 5220 - 5223
(2017/11/06)
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- Site-specific folate conjugation to a cytotoxic protein
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Conjugation to folic acid is known to enhance the uptake of molecules by human cells that over-produce folate receptors. Variants of bovine pancreatic ribonuclease (RNase A) that have attenuated affinity for the endogenous ribonuclease inhibitor protein (
- Smith, Bryan D.,Higgin, Joshua J.,Raines, Ronald T.
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experimental part
p. 5029 - 5032
(2011/10/09)
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- POSITRON EMISSION TOMOGRAPHY IMAGING METHOD
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Described herein are compositions and methods for diagnosing and/or monitoring pathogenic disease states using positron emission tomography, wherein the pathogenic cells uniquely express, preferentially express, or overexpress vitamin receptors. Also described herein are 18F conjugates of vitamins and vitamin receptor- binding analogs and derivatives.
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Page/Page column 30-31
(2008/12/08)
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- PROCESSES FOR MAKING EPOTHILONE COMPOUNDS AND ANALOGS
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The present invention relates to processes for making epothilone compounds and analogs thereof, such as epi-epothilone A or epi-epothilone B, and aziridinyl-epothilone analogs.
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Page/Page column 47
(2009/01/20)
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- AZIRIDINYL-EPOTHILONE COMPOUNDS
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The present invention is directed to aziridinyl epothilone compounds as further described herein, and/or pharmaceutically-acceptable salts and/or solvates thereof having the following Formula: wherein K is —O—, —S—, or —NR7—; A is —(CR8R9)—(CH2)m-Z- wherein Z is —(CHR10)—, —C(═O)—, —C(═O)—C(═O)—, —OC(═O)—, —N(R11)C(═O)—, —SO2—, or —N(R11)SO2—; B1 is hydroxyl or cyano and R1 is hydrogen or B1 and R1 are taken together to form a double bond; R2, R3, and R5 are, independently, hydrogen, alkyl, substituted alkyl, aryl or substituted aryl; or R2 and R3 may be taken together with the carbon to which they are attached to form an optionally substituted cycloalkyl; R4 is hydrogen, alkyl, alkenyl, substituted alkyl, substituted alkenyl, aryl, or substituted aryl; R6 is hydrogen, alkyl or substituted alkyl; R7, R8, R9, R10, R11 and R12 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heterocycloalkyl, substituted heterocycloalkyl, heteroaryl, or substituted heteroaryl; and R13 is aryl, substituted aryl, heteroaryl or substituted heteroaryl.
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Page/Page column 29-30
(2008/06/13)
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- The synthesis of folic acid, multiply labelled with stable isotopes, for bio-availability studies in human nutrition
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Two different methods for the synthesis of folic acid, which are suitable for the incorporation of compounds multiply labelled with stable isotopes, are described. The first method is based on the use of a novel reductive amination to link 2-acetyIamino-4-hydroxy-6-formylpteridine withp-aminobenzoyl-L-glutamic acid. The second method is based on the penultimate formation of an amide bond between Ar-2-acetyl-Ar-10-trifluoroacetyIpteroic acid and dimethyl L-glutamate. Both methods have been used to transform [13C6]aniline into folic acid, labelled with [13C6] in the p-aminobenzoate moiety, and [3,3,4,4-2H4]-L-glutamic acid into folic acid, labelled with [2H4] in the glutamate moiety. Doubly labelled [13C6,2H 4]-p-aminobenzoyl-L-glutamate has also been prepared by the former method.
- Maunder, Peter,Finglas, Paul M.,Mallet, Anthony I.,Mellon, Fred A.,Aaqib Razzaque,Ridge, Brian,Vahteristo, Liisa,Witthoeft, Cornelia
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p. 1311 - 1323
(2007/10/03)
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- Efficient syntheses of pyrofolic acid and pteroyl azide, reagents for the production of carboxyl-differentiated derivatives of folic acid
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Reaction of folic acid (1) with excess trifluoroacetic anhydride provides access to both the previously unknown N10-(trifluoroacetyl)pyrrofolic acid (8) and pyrofolic acid (9). Reaction of either of these materials with hydrazine selectively affords pteroyl hydrazide (13), which may be oxidized to pteroyl azide (27) on a large scale (62% overall from I without the need for chromatography). Treatment of 27 with differentially protected glutamates provides a convenient and high-yielding synthesis of differentially protected, optically pure folates.
- Luo, Jin,Smith, Michael D.,Lantrip, Douglas A.,Wang, Susan,Fuchs
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p. 10004 - 10013
(2007/10/03)
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- Synthesis and biological activity of novel folic acid analogues: Pteroyl- S-alkylhomocysteine sulfoximines
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The synthesis of a novel series of γ-substituted folic acid analogues, pteroyl-S-alkyl-DL-homocysteine (RS)-sulfoximines, and the corresponding S- methylhomocysteine sulfone is described. Side reactions of the sulfoximine groups of the amino acid ester reactants were considered. The correct structures of the isolated target compounds were confirmed by NMR and FAB/MS excluding other alternatives. The replacement of the γ-COOH of the glutamate moiety of folic acid with S-alkylsulfoximine groups of S-methylsulfone did not affect the substrate activity of the vitamin for dihydrofolate reductase. The resulting tetrahydrofolate analogues could serve as cofactors for the thymidylate synthase cycle of murine leukemia L1210 cells in situ. The analogues inhibited the growth of these cells in culture with 2 orders of magnitude lower IC50 values [(2-4) x 10-4 M] than the parent folic acid.
- Harvison,Kalman
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p. 1227 - 1233
(2007/10/02)
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- Folic acid derivatives
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Folic acid derivatives, such as radiolabeled pteroyltyrosine, are conveniently synthesized from either pteroic acid or by the direct condensation of 6-formylpterin with p-aminobenzoyltyrosine methyl ester. The radioiodinated derivatives are particularly useful in competitive protein binding and radioimmuno-assays of folate compounds.
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- Chemical Conversion of Folic Acid to Pteroic Acid
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Treatment of folic acid with acetic anhydride in acetic acid gave a mixture of acetylated azlactones, which are cleaved with mild base at room temperature to give mainly acetylated pteroic acids.Removal of the acetyl groups from the components of this mix
- Temple, Carroll,Rose, Jerry D.,Montgomery, John A.
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p. 3666 - 3667
(2007/10/02)
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- Folic acid derivatives and use in radio-assay
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Novel folic acid derivatives useful for radio-assaying folic acid and its metabolites in biological liquids are prepared from pteroyl-γ-glutamyl-tyrosines by iodination with I125 or I131.
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