Synthesis of N-Substituted phosphoramidic acid esters as “reverse” fosmidomycin analogues
- Adeyemi, Christiana M, Hoppe, Heinrich C, Isaacs, Michelle, Klein, Rosalyn, Lobb, Kevin A, Kaye, Perry T
- Authors: Adeyemi, Christiana M , Hoppe, Heinrich C , Isaacs, Michelle , Klein, Rosalyn , Lobb, Kevin A , Kaye, Perry T
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/443238 , vital:74101 , https://doi.org/10.1016/j.tet.2019.02.003
- Description: An efficient synthetic pathway to a series of novel “reverse” fosmidomycin analogues has been developed, commencing from substituted benzylamines. In these analogues, the fosmidomycin hydroxamate moiety is reversed and the tetrahedral methylene carbon adjacent to the phosphonate moiety is replaced by a nitrogen atom bearing different benzyl groups. The resulting phosphonate esters were designed as potential antimalarial “pro-drugs”.
- Full Text:
- Date Issued: 2019
- Authors: Adeyemi, Christiana M , Hoppe, Heinrich C , Isaacs, Michelle , Klein, Rosalyn , Lobb, Kevin A , Kaye, Perry T
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/443238 , vital:74101 , https://doi.org/10.1016/j.tet.2019.02.003
- Description: An efficient synthetic pathway to a series of novel “reverse” fosmidomycin analogues has been developed, commencing from substituted benzylamines. In these analogues, the fosmidomycin hydroxamate moiety is reversed and the tetrahedral methylene carbon adjacent to the phosphonate moiety is replaced by a nitrogen atom bearing different benzyl groups. The resulting phosphonate esters were designed as potential antimalarial “pro-drugs”.
- Full Text:
- Date Issued: 2019
Synthesis and anti-parasitic activity of C-benzylated (N-arylcarbamoyl) alkylphosphonate esters
- Adeyemi, Christiana Modupe, Isaacs, Michelle, Mnkandhla, Dumisani, Krause, Rui W M, Klein, Rosalyn, Hoppe, Heinrich C, Lobb, Kevin A, Kaye, Perry T
- Authors: Adeyemi, Christiana Modupe , Isaacs, Michelle , Mnkandhla, Dumisani , Krause, Rui W M , Klein, Rosalyn , Hoppe, Heinrich C , Lobb, Kevin A , Kaye, Perry T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125641 , vital:35803 , https://doi.org/10.1016/j.tet.2017.01.045
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl)phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
- Date Issued: 2017
- Authors: Adeyemi, Christiana Modupe , Isaacs, Michelle , Mnkandhla, Dumisani , Krause, Rui W M , Klein, Rosalyn , Hoppe, Heinrich C , Lobb, Kevin A , Kaye, Perry T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125641 , vital:35803 , https://doi.org/10.1016/j.tet.2017.01.045
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl)phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
- Date Issued: 2017
Application of Baylis-Hillman methodology in the direct construction of chromone derivatives
- Faridoon, H, Olomola, Temitope O, Klein, Rosalyn, Kaye, Perry T
- Authors: Faridoon, H , Olomola, Temitope O , Klein, Rosalyn , Kaye, Perry T
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/442488 , vital:73992 , https://doi.org/10.1016/j.tet.2015.11.039
- Description: Pyridinium chlorochromate oxidation of Baylis-Hillman-derived tert-butyl 2H-chromene-3-carboxylates affords chromone-3-carboxylate esters, providing the first application of Baylis-Hillman methodology in a direct and convenient three-step synthesis of chromone derivatives.
- Full Text:
- Date Issued: 2016
- Authors: Faridoon, H , Olomola, Temitope O , Klein, Rosalyn , Kaye, Perry T
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/442488 , vital:73992 , https://doi.org/10.1016/j.tet.2015.11.039
- Description: Pyridinium chlorochromate oxidation of Baylis-Hillman-derived tert-butyl 2H-chromene-3-carboxylates affords chromone-3-carboxylate esters, providing the first application of Baylis-Hillman methodology in a direct and convenient three-step synthesis of chromone derivatives.
- Full Text:
- Date Issued: 2016
Elucidating Latent Mechanistic Complexity in Competing Acid-Catalyzed Reactions of Salicylaldehyde-Derived Baylis–Hillman Adducts
- Olomola, Temitope O, Klein, Rosalyn, Caira, Mino, R, Kaye, Perry T
- Authors: Olomola, Temitope O , Klein, Rosalyn , Caira, Mino, R , Kaye, Perry T
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/442596 , vital:74010 , https://doi.org/10.1021/acs.joc.5b02372
- Description: 1H NMR-based kinetic studies have revealed the latent mechanistic complexity of deceptively simple hydrochloric acid-catalyzed reactions of salicylaldehyde-derived Baylis–Hillman adducts. Reactions conducted at 0 °C afforded 2-(chloromethyl)cinnamic acid derivatives as the major products and the corresponding 3-(chloromethyl)coumarin derivatives as the minor products. In reactions conducted in refluxing acetic acid, however, the 3-(chloromethyl)coumarin derivatives are the sole products. Variable-temperature 1H NMR analysis permitted the determination of the rate constants and kinetic parameters involved in the pseudo-first-order formation of (Z)-2-(chloromethyl)-3-(2-hydroxyphenyl)-2-propenoic acid. The kinetic data clearly preclude the operation of classical kinetic versus thermodynamic control and indicate the operation of three independent reaction pathways. Theoretical studies of these pathways undertaken at the B3LYP/6-31G(d) level permitted rationalization of the experimental data and provided insights into the possible mechanism of the enzymic E–Z isomerization and cyclization of (E)-cinnamic acid analogues to afford coumarins.
- Full Text:
- Date Issued: 2016
- Authors: Olomola, Temitope O , Klein, Rosalyn , Caira, Mino, R , Kaye, Perry T
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/442596 , vital:74010 , https://doi.org/10.1021/acs.joc.5b02372
- Description: 1H NMR-based kinetic studies have revealed the latent mechanistic complexity of deceptively simple hydrochloric acid-catalyzed reactions of salicylaldehyde-derived Baylis–Hillman adducts. Reactions conducted at 0 °C afforded 2-(chloromethyl)cinnamic acid derivatives as the major products and the corresponding 3-(chloromethyl)coumarin derivatives as the minor products. In reactions conducted in refluxing acetic acid, however, the 3-(chloromethyl)coumarin derivatives are the sole products. Variable-temperature 1H NMR analysis permitted the determination of the rate constants and kinetic parameters involved in the pseudo-first-order formation of (Z)-2-(chloromethyl)-3-(2-hydroxyphenyl)-2-propenoic acid. The kinetic data clearly preclude the operation of classical kinetic versus thermodynamic control and indicate the operation of three independent reaction pathways. Theoretical studies of these pathways undertaken at the B3LYP/6-31G(d) level permitted rationalization of the experimental data and provided insights into the possible mechanism of the enzymic E–Z isomerization and cyclization of (E)-cinnamic acid analogues to afford coumarins.
- Full Text:
- Date Issued: 2016
Photocatalysis of 4-nitrophenol using zinc phthalocyanine complexes
- Marais, Eloïse, Klein, Rosalyn, Antunes, Edith M, Nyokong, Tebello
- Authors: Marais, Eloïse , Klein, Rosalyn , Antunes, Edith M , Nyokong, Tebello
- Date: 2007
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/281286 , vital:55709 , xlink:href="https://doi.org/10.1016/j.molcata.2006.07.055"
- Description: Photodegradation of 4-nitrophenol (4-Np) in the presence of zinc tetrasulfophthalocyanine (ZnPcS4), zinc octacarboxyphthalocyanine (ZnPc(COOH)8) and a sulfonated ZnPc containing a mixture of differently sulfonated derivatives (ZnPcSmix), as photocatalysts is reported. ZnPcSmix is the most effective catalyst in terms of a high quantum yield for 4-Np degradation and the stability of the catalyst. However ZnPc(COOH)8 degrades readily during the catalysis, but it has a higher quantum yield (Φ4-Np) for 4-Np degradation than the rest of the complexes. The Φ4-Np values were closely related to the singlet oxygen quantum yields ΦΔ and hence aggregation. The rate constants for the reaction with 4-Np were kr = 0.67 × 106 mol−1 dm3 s−1 for ZnPcSmix and 2.8 × 108 mol−1 dm3 s−1 for ZnPc(COOH)8.
- Full Text:
- Date Issued: 2007
- Authors: Marais, Eloïse , Klein, Rosalyn , Antunes, Edith M , Nyokong, Tebello
- Date: 2007
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/281286 , vital:55709 , xlink:href="https://doi.org/10.1016/j.molcata.2006.07.055"
- Description: Photodegradation of 4-nitrophenol (4-Np) in the presence of zinc tetrasulfophthalocyanine (ZnPcS4), zinc octacarboxyphthalocyanine (ZnPc(COOH)8) and a sulfonated ZnPc containing a mixture of differently sulfonated derivatives (ZnPcSmix), as photocatalysts is reported. ZnPcSmix is the most effective catalyst in terms of a high quantum yield for 4-Np degradation and the stability of the catalyst. However ZnPc(COOH)8 degrades readily during the catalysis, but it has a higher quantum yield (Φ4-Np) for 4-Np degradation than the rest of the complexes. The Φ4-Np values were closely related to the singlet oxygen quantum yields ΦΔ and hence aggregation. The rate constants for the reaction with 4-Np were kr = 0.67 × 106 mol−1 dm3 s−1 for ZnPcSmix and 2.8 × 108 mol−1 dm3 s−1 for ZnPc(COOH)8.
- Full Text:
- Date Issued: 2007
Synthesis of triprenylated toluquinone and toluhydroquinone metabolites from a marine-derived Penicillium fungus
- Scheepers, Brent A, Klein, Rosalyn, Davies-Coleman, Michael T
- Authors: Scheepers, Brent A , Klein, Rosalyn , Davies-Coleman, Michael T
- Date: 2006
- Language: English
- Type: Article
- Identifier: vital:6592 , http://hdl.handle.net/10962/d1004341
- Description: Two triprenylated toluquinone and toluhydroquinone marine fungal metabolites, 5-methyl-2-[(2′E,6′E)-3′,7′,11′-trimethyl-2′,6′,10′-dodecatrienyl]-2,5-cyclohexadiene-1,4-dione and 5-methyl-2-[(2′E,6′E)-3,7,11-trimethyl-2′,6′,10′-dodecatrienyl]-1,4-benzenediol, were synthesized in four and five steps, respectively, from 2-methyl-1,4-benzoquinone. The synthesis extends the applicability of the oxidative ether cleavage of hydroquinone dimethyl ethers with argentic oxide under acidic conditions to include the oxidative demethylation of polyprenylated-1,4-dimethoxy-toluhydroquinones with a quantitative survival of the oxidation- and acid-sensitive polyprenyl side chain. Graphical abstract: Marine fungal metabolites 1 and 2 were synthesized from 2-methyl-1,4-benzoquinone in four and five steps, respectively. [For graphic image see full-text version]
- Full Text:
- Date Issued: 2006
- Authors: Scheepers, Brent A , Klein, Rosalyn , Davies-Coleman, Michael T
- Date: 2006
- Language: English
- Type: Article
- Identifier: vital:6592 , http://hdl.handle.net/10962/d1004341
- Description: Two triprenylated toluquinone and toluhydroquinone marine fungal metabolites, 5-methyl-2-[(2′E,6′E)-3′,7′,11′-trimethyl-2′,6′,10′-dodecatrienyl]-2,5-cyclohexadiene-1,4-dione and 5-methyl-2-[(2′E,6′E)-3,7,11-trimethyl-2′,6′,10′-dodecatrienyl]-1,4-benzenediol, were synthesized in four and five steps, respectively, from 2-methyl-1,4-benzoquinone. The synthesis extends the applicability of the oxidative ether cleavage of hydroquinone dimethyl ethers with argentic oxide under acidic conditions to include the oxidative demethylation of polyprenylated-1,4-dimethoxy-toluhydroquinones with a quantitative survival of the oxidation- and acid-sensitive polyprenyl side chain. Graphical abstract: Marine fungal metabolites 1 and 2 were synthesized from 2-methyl-1,4-benzoquinone in four and five steps, respectively. [For graphic image see full-text version]
- Full Text:
- Date Issued: 2006
Asymmetric α-alkylation reactions
- Authors: Klein, Rosalyn
- Date: 2000
- Subjects: Asymmetric synthesis , Alkylation , Chemical reactions
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4405 , http://hdl.handle.net/10962/d1006710 , Asymmetric synthesis , Alkylation , Chemical reactions
- Description: A novel camphor-derived hydroxy ketal 138 has been developed as a crural auxiliary, and used to prepare a series of six carboxylic esters of increasing steric bulk. The α-benzylation of this series of esters was achieved with diastereoselectivities of 59 - 83% d. e. and in 39 - 48% material yield. These results compared very favourably with those obtained in earlier studies using a regioisomeric analogue as the chiral auxiliary. Computer.modelling studies of the putative enolate intermediate has provided some insight into the possible mode of electrophilic attack at the α-carbon and the roles of the ketal protecting group and the lithium cation in these asymmetric transformations. In a related investigation, based on earlier work, a camphor-derived imino lactone has provided convenient access to α-alkyl α-amino acids, the imino lactone serving as a masked glycine equivalent. Using straight chain primary alkyl iodides [RI; R = Me, Et, Pr, Bu, CH₃(CH₂)₄ and CH₃(CH₄)₅], alkylation of the potassium enolate of the camphor-derived imino lactone was effected with 54 - 89% d.e. and in 54 - 87% material yield. Four novel alkylated derivatives were synthesised using isopropyl iodide, sec-butyl iodide and allyl iodide, the latter reagent resulting in both the monoallylated and diallylated products. While very good diastereoselectivities were achieved (83 - 88% d. e.) in these reactions, the material yields from reaction with the secondary alkyl iodides were low (31- 35%) due, presumably, to their decreased electrophilicity. Computer modelling studies of the enolate were carried out and support the hypothesis of endo attack by the electrophile on the enolate intermediate. These studies also indicate the possibility of coordination of the postassium cation to the endocyclic ester oxygen, thus effectively anchoring the bulky cation away from the reaction site.
- Full Text:
- Date Issued: 2000
- Authors: Klein, Rosalyn
- Date: 2000
- Subjects: Asymmetric synthesis , Alkylation , Chemical reactions
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4405 , http://hdl.handle.net/10962/d1006710 , Asymmetric synthesis , Alkylation , Chemical reactions
- Description: A novel camphor-derived hydroxy ketal 138 has been developed as a crural auxiliary, and used to prepare a series of six carboxylic esters of increasing steric bulk. The α-benzylation of this series of esters was achieved with diastereoselectivities of 59 - 83% d. e. and in 39 - 48% material yield. These results compared very favourably with those obtained in earlier studies using a regioisomeric analogue as the chiral auxiliary. Computer.modelling studies of the putative enolate intermediate has provided some insight into the possible mode of electrophilic attack at the α-carbon and the roles of the ketal protecting group and the lithium cation in these asymmetric transformations. In a related investigation, based on earlier work, a camphor-derived imino lactone has provided convenient access to α-alkyl α-amino acids, the imino lactone serving as a masked glycine equivalent. Using straight chain primary alkyl iodides [RI; R = Me, Et, Pr, Bu, CH₃(CH₂)₄ and CH₃(CH₄)₅], alkylation of the potassium enolate of the camphor-derived imino lactone was effected with 54 - 89% d.e. and in 54 - 87% material yield. Four novel alkylated derivatives were synthesised using isopropyl iodide, sec-butyl iodide and allyl iodide, the latter reagent resulting in both the monoallylated and diallylated products. While very good diastereoselectivities were achieved (83 - 88% d. e.) in these reactions, the material yields from reaction with the secondary alkyl iodides were low (31- 35%) due, presumably, to their decreased electrophilicity. Computer modelling studies of the enolate were carried out and support the hypothesis of endo attack by the electrophile on the enolate intermediate. These studies also indicate the possibility of coordination of the postassium cation to the endocyclic ester oxygen, thus effectively anchoring the bulky cation away from the reaction site.
- Full Text:
- Date Issued: 2000
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