Persistent Link:
http://hdl.handle.net/10150/187050
Title:
Synthetic approaches toward natural product synthesis.
Author:
Liu, Yunqi.
Issue Date:
1995
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:
1,2-Dithiolan-3-one-1-oxide exists in antihumor antibiotic leinamycin and can cause DNA cleavage in the presence of thiols. Diastereoselective synthesis of this unique ring system has been achieved by low temperature oxidation of the corresponding 1,2-dithiolan-3-ones with 3,3-dimethyldioxirane. 5-Methyl-1,2-dithiolan-3-one-1-oxides were synthesized by oxidation of 5-methyl-1,2-dithiolan-3-one with 3,3-dimethyldioxirane. Eu(fod)₃ and C₆D₆ induced proton chemical shift studies showed that the major isomer in the product has a trans sulfoxide relative to the 5-methyl group. Low temperature oxidation of 4-substituted-amino-5,5-dimethyl-1,2-dithiolan-3-ones by 3,3-dimethyldioxirane preferentially led to the corresponding trans-1,2-dithiolan-3-one-1-oxides. This assignment was made on the basis of a X-ray crystallographic structure study. Formation of azlactones as well as 1,2-dithiolan-3-one-1,1-dioxide were also observed when some substituted 1,2-dithiolan-3-ones were oxidized by 3,3-ditnethyldioxirane. Three 2,2-dimethyl-1,3-dithian-4-ones were synthesized by SnCl₄ mediated condensation of β-mercaptothioacids and acetone. Oxidation of 2,2,6-trimethyl-1,3-dithian-4-one with Ce(IV) did not give 1,2-dithiolan-3-one or 1,2-dithiolan-3-one-1-oxides as anticipated; 1,3-dithian-5-en-4-one was detected as the product instead. Synthetic approaches toward loline were explored. Intramolecular photoaddition of bicyclic olefinic N-nitrosamine did not give the desired product. An epoxide approach did not furnish loline due to unsuccessful epoxide ring opening by azide ion. In the urea approach, the tertiary nitrogen of the bicyclic urea preferentially undergoes a transannular iodocyclization. The same results were obtained by halocyclizing bis-silylimidate or mono-silylimidate of the bicyclic urea.
Type:
text; Dissertation-Reproduction (electronic)
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Chemistry; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Glass, Richard S.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleSynthetic approaches toward natural product synthesis.en_US
dc.creatorLiu, Yunqi.en_US
dc.contributor.authorLiu, Yunqi.en_US
dc.date.issued1995en_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.abstract1,2-Dithiolan-3-one-1-oxide exists in antihumor antibiotic leinamycin and can cause DNA cleavage in the presence of thiols. Diastereoselective synthesis of this unique ring system has been achieved by low temperature oxidation of the corresponding 1,2-dithiolan-3-ones with 3,3-dimethyldioxirane. 5-Methyl-1,2-dithiolan-3-one-1-oxides were synthesized by oxidation of 5-methyl-1,2-dithiolan-3-one with 3,3-dimethyldioxirane. Eu(fod)₃ and C₆D₆ induced proton chemical shift studies showed that the major isomer in the product has a trans sulfoxide relative to the 5-methyl group. Low temperature oxidation of 4-substituted-amino-5,5-dimethyl-1,2-dithiolan-3-ones by 3,3-dimethyldioxirane preferentially led to the corresponding trans-1,2-dithiolan-3-one-1-oxides. This assignment was made on the basis of a X-ray crystallographic structure study. Formation of azlactones as well as 1,2-dithiolan-3-one-1,1-dioxide were also observed when some substituted 1,2-dithiolan-3-ones were oxidized by 3,3-ditnethyldioxirane. Three 2,2-dimethyl-1,3-dithian-4-ones were synthesized by SnCl₄ mediated condensation of β-mercaptothioacids and acetone. Oxidation of 2,2,6-trimethyl-1,3-dithian-4-one with Ce(IV) did not give 1,2-dithiolan-3-one or 1,2-dithiolan-3-one-1-oxides as anticipated; 1,3-dithian-5-en-4-one was detected as the product instead. Synthetic approaches toward loline were explored. Intramolecular photoaddition of bicyclic olefinic N-nitrosamine did not give the desired product. An epoxide approach did not furnish loline due to unsuccessful epoxide ring opening by azide ion. In the urea approach, the tertiary nitrogen of the bicyclic urea preferentially undergoes a transannular iodocyclization. The same results were obtained by halocyclizing bis-silylimidate or mono-silylimidate of the bicyclic urea.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairGlass, Richard S.en_US
dc.contributor.committeememberMash, Eugene A.en_US
dc.contributor.committeememberEnemark, John H.en_US
dc.contributor.committeememberBates, Robert B.en_US
dc.identifier.proquest9531074en_US
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