Cyclodepsipeptides from a Kenyan marine cyanobacterium
- Authors: Dzeha, Thomas Mwambire
- Date: 2003
- Subjects: Cyanobacteria , Stereochemistry , Natural products -- Kenya
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4303 , http://hdl.handle.net/10962/d1004961 , Cyanobacteria , Stereochemistry , Natural products -- Kenya
- Description: An examination of an organic extract of the cyanobacterium Lyngbya majuscula collected from Wasini Island off the southern Kenyan coast led to the isolation of the known cyclodepsipeptide antanapeptin A (7), recently isolated from a Madagascan collection of L. majuscula, and a new bioactive cyclodepsipeptide, homodolastatin 16 (42). Although L. majuscula is a common, pantropical cyanobacterium this study represents the first investigation of the natural product chemistry of a Kenyan population of L. majuscula. The structures of the two cyclodepsipeptides were determined from 2D NMR and mass spectrometry data. The L- stereochemistry of the proline, valine, and N-methylphenylalanine amino acids in 7 and the L – proline configuration in 42, was confirmed by Marfey’s HPLC method. Chiral GC was used to determine the absolute stereochemistry of the hydroxyisovaleric acid moiety in 7 and 42, the lactate residue in 42 and tentatively propose an L-stereochemistry for the Nmethylisoleucine amino acid in 42. Homodolastatin 16, a higher homologue of the potential anti-cancer agent, dolastatin 16, exhibited moderate activity against two oesophageal cancer cell lines.
- Full Text:
- Date Issued: 2003
- Authors: Dzeha, Thomas Mwambire
- Date: 2003
- Subjects: Cyanobacteria , Stereochemistry , Natural products -- Kenya
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4303 , http://hdl.handle.net/10962/d1004961 , Cyanobacteria , Stereochemistry , Natural products -- Kenya
- Description: An examination of an organic extract of the cyanobacterium Lyngbya majuscula collected from Wasini Island off the southern Kenyan coast led to the isolation of the known cyclodepsipeptide antanapeptin A (7), recently isolated from a Madagascan collection of L. majuscula, and a new bioactive cyclodepsipeptide, homodolastatin 16 (42). Although L. majuscula is a common, pantropical cyanobacterium this study represents the first investigation of the natural product chemistry of a Kenyan population of L. majuscula. The structures of the two cyclodepsipeptides were determined from 2D NMR and mass spectrometry data. The L- stereochemistry of the proline, valine, and N-methylphenylalanine amino acids in 7 and the L – proline configuration in 42, was confirmed by Marfey’s HPLC method. Chiral GC was used to determine the absolute stereochemistry of the hydroxyisovaleric acid moiety in 7 and 42, the lactate residue in 42 and tentatively propose an L-stereochemistry for the Nmethylisoleucine amino acid in 42. Homodolastatin 16, a higher homologue of the potential anti-cancer agent, dolastatin 16, exhibited moderate activity against two oesophageal cancer cell lines.
- Full Text:
- Date Issued: 2003
Structural and stereochemical investigations of terrestrial and marine pyrone metabolites
- Authors: Collett, Lynne Alison
- Date: 1997
- Subjects: Metabolites , Stereochemistry , Siphonaria
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4348 , http://hdl.handle.net/10962/d1005013 , Metabolites , Stereochemistry , Siphonaria
- Description: This thesis presents an investigation into the chemistry of 6 substituted 5, 6-dihydro-a-pyrone compounds. A comprehensive review of these compounds was published in 1989 and the subsequent literature is covered in an updated review presented below. Eight 6-substituted 5,6-dihydro-a-pyrone metabolites from three different South African plant species Cryptocarya latijolia, Syncolostemon densiflorus, and Syncolostemon argenteus have been the subject of structural and stereochemical investigations. The absolute stereochemistry of the known compound "triacetate" from C. latijolia has been established as 6R-[2R,4S,6S-(triacetyloxy)heptylJ-5,6-dihydro-2H-pyran-2-one (74) using CD and acetonide formation with subsequent application of the modified Moshers method. The absolute stereochemistry of the related metabolite "diacetate", also from C. latijolia, has been assigned as 6R-[2S,4S-diacetyloxypentylJ-5,6-dihydro-2H-pyran-2-one (76). In addition, the outstanding stereochemistry at C-5' in syndenolide, from S. densiflorus, followed from conversion to its diacetonide and subsequent NMR analysis. Syndenolide is therefore 6R-[5S-(acetoxy)-IR,2R,3S-(trihydroxy)-heptylJ-5,6- dihydro-2H -pyran-2-one. The genus Syncolostemon has proved to be a rich source of a-pyrone compounds and the chemistry of S. argenteus, not investigated previously, was examined as part of an ongoing search for new 5,6-dihydro-a-pyrones. The study yielded five new a-pyrone natural products, synargentolide A-E. The structure of synargentolide A (82) has been assigned as 6R[4R,5R,6S-triacetyloxy-lE-heptenylJ-5,6-dihydro-2H-pyran-2-one using CD and NMR techniques. The structures of synargentolide B (87), C (92) and E (94) also followed from a detailed NMR analysis and the stereochemistry tentatively assigned based on CD and NMR data. Synargentolide D (93) was thermally unstable, and a paucity of material prevented stereochemical investigations, however the structure was determined from initial NMR analysis. The marine molluscs of the genus Siphonaria have only become the subject of chemical studies in the last fifteen years. These molluscs characteristically produce polypropionate type natural products. A review of Siphonarian polypropionate metabolites containing a pyrone functionality is presented. Examination of an endemic South African species Siphonaria serrata yielded one novel polypropionate metabolite containing a ),-pyrone functionality, siserrone A (131). The structure of this compound was unambiguously established using standard NMR experiments. The relative stereochemisty of the hemi-ketal moiety was assigned from a careful analysis of the ROESY NMR spectrum and the stereochemisty of the acyclic portion determined from a comparison of the 13C and 'H NMR data of a degradation product with the corresponding data of a synthetic compound. It was also established that the modified Moshers method could not be used to determine the absolute stereochemistry of the secondary hydroxy I substituent at C-11. The absolute stereochemistry of 131 was thus assigned in accordance with the proven stereochemistry of Siphonarian metabolites.
- Full Text:
- Date Issued: 1997
- Authors: Collett, Lynne Alison
- Date: 1997
- Subjects: Metabolites , Stereochemistry , Siphonaria
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4348 , http://hdl.handle.net/10962/d1005013 , Metabolites , Stereochemistry , Siphonaria
- Description: This thesis presents an investigation into the chemistry of 6 substituted 5, 6-dihydro-a-pyrone compounds. A comprehensive review of these compounds was published in 1989 and the subsequent literature is covered in an updated review presented below. Eight 6-substituted 5,6-dihydro-a-pyrone metabolites from three different South African plant species Cryptocarya latijolia, Syncolostemon densiflorus, and Syncolostemon argenteus have been the subject of structural and stereochemical investigations. The absolute stereochemistry of the known compound "triacetate" from C. latijolia has been established as 6R-[2R,4S,6S-(triacetyloxy)heptylJ-5,6-dihydro-2H-pyran-2-one (74) using CD and acetonide formation with subsequent application of the modified Moshers method. The absolute stereochemistry of the related metabolite "diacetate", also from C. latijolia, has been assigned as 6R-[2S,4S-diacetyloxypentylJ-5,6-dihydro-2H-pyran-2-one (76). In addition, the outstanding stereochemistry at C-5' in syndenolide, from S. densiflorus, followed from conversion to its diacetonide and subsequent NMR analysis. Syndenolide is therefore 6R-[5S-(acetoxy)-IR,2R,3S-(trihydroxy)-heptylJ-5,6- dihydro-2H -pyran-2-one. The genus Syncolostemon has proved to be a rich source of a-pyrone compounds and the chemistry of S. argenteus, not investigated previously, was examined as part of an ongoing search for new 5,6-dihydro-a-pyrones. The study yielded five new a-pyrone natural products, synargentolide A-E. The structure of synargentolide A (82) has been assigned as 6R[4R,5R,6S-triacetyloxy-lE-heptenylJ-5,6-dihydro-2H-pyran-2-one using CD and NMR techniques. The structures of synargentolide B (87), C (92) and E (94) also followed from a detailed NMR analysis and the stereochemistry tentatively assigned based on CD and NMR data. Synargentolide D (93) was thermally unstable, and a paucity of material prevented stereochemical investigations, however the structure was determined from initial NMR analysis. The marine molluscs of the genus Siphonaria have only become the subject of chemical studies in the last fifteen years. These molluscs characteristically produce polypropionate type natural products. A review of Siphonarian polypropionate metabolites containing a pyrone functionality is presented. Examination of an endemic South African species Siphonaria serrata yielded one novel polypropionate metabolite containing a ),-pyrone functionality, siserrone A (131). The structure of this compound was unambiguously established using standard NMR experiments. The relative stereochemisty of the hemi-ketal moiety was assigned from a careful analysis of the ROESY NMR spectrum and the stereochemisty of the acyclic portion determined from a comparison of the 13C and 'H NMR data of a degradation product with the corresponding data of a synthetic compound. It was also established that the modified Moshers method could not be used to determine the absolute stereochemistry of the secondary hydroxy I substituent at C-11. The absolute stereochemistry of 131 was thus assigned in accordance with the proven stereochemistry of Siphonarian metabolites.
- Full Text:
- Date Issued: 1997
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