Synthesis of carborane analogues of γ-aminobutanoic acid

Ol’shevskaya, V. A.; Ayuob, Rami; Brechko, Zhanna G.; Petrovskii, P. V.; Kononova, Elena G.; Левит, Г. Л.; Краснов, В. П.; Charushin, Valery N.; Чупахин, О. Н.; Калинин, В. Н.

doi:10.1016/j.jorganchem.2005.01.056

Cited by 25 publications

(4 citation statements)

References 8 publications

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“…Coupling of racemic N Boc amino acid 5 with N α benzyloxycarbonyl(Z) L lysine methyl ester (14) in the presence of DCC and HOBt gave amide 15 as a mixture of diastereomers (HPLC on silica gel).…”

Section: Methodsmentioning

confidence: 99%

“…1,2 ) were used. Carborane derivatives containing ami no and/or carboxy groups, including 3 amino 1,2 dicar ba closo dodecaborane (1) 13 and 2 (3 amino 1,2 dicar ba closo dodecaboran 1 yl)acetic acid (2) 14 are promis ing objects for the synthesis of novel BNCT agents Amino acids and peptides are essential components of proliferating malignant cells. The mechanisms of active transport are most efficient for L amino acid derivatives containing free carboxy and α amino groups.…”

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Synthesis of novel carboranyl derivatives of α-amino acids

et al. 2010

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New routes to closo carboranyl derivatives of L lysine and L glutamic acid with free α NH 2 groups were proposed.Boron neutron capture therapy (BNCT) is a modern approach to cancer treatment that is under intensive de velopment. This is based on capturing thermal neutrons by 10 B nuclei followed by fission of radioactive 11 B iso topes emitting α particles, which cause local damage to the target cells. This results in selective death of cells con taining boron compounds. Intensive relevant investiga tions in the last decade were aimed at searching for new BNCT agents. 1-4 In this respect, dicarba closo dodecab orane (carborane) derivatives are very promising. Essen tial requirements to BNCT agents include selective deliv ery to tumor cells and the ability to be retained and accu mulate in these cells. In previous attempts at designing such agents, carborane containing derivatives of biomol ecules (nucleosides, 5-7 porphyrins, 8,9 amino acids, 10-12 etc. 1,2 ) were used. Carborane derivatives containing ami no and/or carboxy groups, including 3 amino 1,2 dicar ba closo dodecaborane (1) 13 and 2 (3 amino 1,2 dicar ba closo dodecaboran 1 yl)acetic acid (2) 14 are promis ing objects for the synthesis of novel BNCT agents Amino acids and peptides are essential components of proliferating malignant cells. The mechanisms of active transport are most efficient for L amino acid derivatives containing free carboxy and α amino groups. 15, 16 Recent investigations showed that tumor cells are char acterized by increased and selective uptake of folic acid. 17-19The highest affinity for folate receptors is exhibited by folic acid derivatives with the modified γ carboxy group of the L glutamic acid fragment and the free α carboxy group. 19-22Targeted introduction of carborane residues into ami no acids containing additional functional groups (e.g., lysine or glutamic acid) can be an important step in the preparation of promising BNCT agents and thus is of con siderable interest.The goal of the present work was to develop methods for the synthesis of carborane containing derivatives of L lysine and N γ (1,2 dicarba closo dodecaboran 3 yl) L glutamic acid. Results and DiscussionWe used (1,2 dicarba closo dodecaboran 1 yl)acetic acid (3) and N protected (3 amino 1,2 dicarba closo dodecaboran 1 yl)acetic acids 4 (see Ref. 14) and 5 (see Ref. 23) as the starting carborane containing reagents for the preparation of carboranyl derivatives of L lysine (Scheme 1). The starting L lysine derivative used was N α TFA L lysine methyl ester (6), because the N α TFA and COOMe protecting groups can simultaneously be re moved under mild conditions without destruction of the closo carborane cage. Earlier, in the synthesis of N [(3 amino 1,2 dicarba closo dodecaboran 1 yl)acetyl] deriv atives of amino acids, we have found that closo carboranes withstand basic hydrolysis under mild conditions. 23Coupling of carboranylacetic acids 3-5 with com pound 6 at room temperature using N,N´ dicyclohexyl carbodiimide (DCC) in the presence of 1 hydroxybenzot ri...

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Synthesis of novel carboranyl derivatives of α-amino acids

et al. 2010

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“…NH 3 has been found to efficiently dehalogenate these halogenated compounds even in the presence of water, thus converting them into less toxic material. 9 (H) Synthesis of aminophenanthridines from anilines: Diversely substituted phenanthridines have been obtained by condensation of anilines with 2-chlorobenzonitriles promoted by sodium amide in liquid ammonia. 10 liq.…”

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Synthetic Applications of Sodium in Liquid Ammonia

Raikar¹

2007

Synlett

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“…Removal of ester groups SCHEME 4 from the amino acid moieties leads to the amides with free amino-acid COOH groups which can be subjected to further modifications. -1,2-dicarba-closo-dodecaboranes 2-4 were prepared according to the previously described procedure 5 . tert-Butyl D-valinate (6) was prepared as described previously 7 .…”

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Synthesis of N-[(3-Amino-1,2-dicarba-closo-dodecaboran-1-yl)acetyl] Derivatives of α-Amino Acids

Левит

Краснов

Gruzdev

et al. 2007

Collect. Czech. Chem. Commun.

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The N- [(3-amino-1,2-dicarba-closo-dodecaboran-1-yl)acetyl] derivatives of α-amino acids were prepared starting from N-protected (Ac, Form, Bz, and Boc) 3-amino-1-(carboxymethyl)-o-carboranes and alkyl esters of natural α-amino acids using the carbodiimide method of coupling and removing the ester groups. All the amides obtained were diastereoisomeric mixtures. Some diastereoisomers were separated and the assignment of the absolute configuration of aminocarborane fragments was performed by X-ray crystallography.

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Synthesis of carborane analogues of γ-aminobutanoic acid

Cited by 25 publications

References 8 publications

Synthesis of novel carboranyl derivatives of α-amino acids

Synthesis of novel carboranyl derivatives of α-amino acids

Synthetic Applications of Sodium in Liquid Ammonia

Synthesis of N-[(3-Amino-1,2-dicarba-closo-dodecaboran-1-yl)acetyl] Derivatives of α-Amino Acids

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