Synthesis of dolastatin 11 and analogs: Molecular modeling studies in this series

Persistent Link:
http://hdl.handle.net/10150/282652
Title:
Synthesis of dolastatin 11 and analogs: Molecular modeling studies in this series
Author:
Stessman, Chad Christian, 1972-
Issue Date:
1998
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The synthesis of dolastatin 11 was repeated on a much larger scale. Most of the yields and reaction conditions in the original synthesis were improved upon. Several problems that arose in the scale up were solved. The synthetic dolastatin 11 was obtained for the first time. The synthetic dolastatin 11 had good activity against a variety of cancer cell lines. The structure of the major by-product of the dolastatin 11 synthesis was determined. Several analogs of dolastatin 11 were synthesized. Testing results on the beta-alanine analog of dolastatin 11 showed it to have similar activity to the natural product. Molecular modeling studies on dolastatin 11 in both chloroform and water were pursued. The molecular modeling structure results in chloroform were consistent with NOE and coupling constant evidence. Molecular modeling calculations were also carried out on several dolastatin 11 analogs. These calculations combined with the testing results on dolastatin 11 and its beta-alanine analog indicate that the lowest energy conformation calculated for dolastatin 11 in chloroform may be the most active conformation.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Pharmacology.; Chemistry, Biochemistry.; Chemistry, Organic.; Health Sciences, Oncology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
Bates, Robert B.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleSynthesis of dolastatin 11 and analogs: Molecular modeling studies in this seriesen_US
dc.creatorStessman, Chad Christian, 1972-en_US
dc.contributor.authorStessman, Chad Christian, 1972-en_US
dc.date.issued1998en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe synthesis of dolastatin 11 was repeated on a much larger scale. Most of the yields and reaction conditions in the original synthesis were improved upon. Several problems that arose in the scale up were solved. The synthetic dolastatin 11 was obtained for the first time. The synthetic dolastatin 11 had good activity against a variety of cancer cell lines. The structure of the major by-product of the dolastatin 11 synthesis was determined. Several analogs of dolastatin 11 were synthesized. Testing results on the beta-alanine analog of dolastatin 11 showed it to have similar activity to the natural product. Molecular modeling studies on dolastatin 11 in both chloroform and water were pursued. The molecular modeling structure results in chloroform were consistent with NOE and coupling constant evidence. Molecular modeling calculations were also carried out on several dolastatin 11 analogs. These calculations combined with the testing results on dolastatin 11 and its beta-alanine analog indicate that the lowest energy conformation calculated for dolastatin 11 in chloroform may be the most active conformation.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectChemistry, Biochemistry.en_US
dc.subjectChemistry, Organic.en_US
dc.subjectHealth Sciences, Oncology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorBates, Robert B.en_US
dc.identifier.proquest9831817en_US
dc.identifier.bibrecord.b38626007en_US
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