國立高雄大學圖資館 |

登入

回首頁

Synthetic study of C-1027-CHR.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Synthetic study of C-1027-CHR.
作者:	Jiang, Yu.
面頁冊數:	265 p.
附註:	Adviser: Martin Semmelhack.
附註:	Source: Dissertation Abstracts International, Volume: 63-10, Section: B, page: 4681.
Contained By:	Dissertation Abstracts International63-10B.
標題:	Chemistry, Organic.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3067150
ISBN:	0493866280

Synthetic study of C-1027-CHR.
Jiang, Yu.

Synthetic study of C-1027-CHR. [electronic resource] - 265 p.

Adviser: Martin Semmelhack.

Thesis (Ph.D.)--Princeton University, 2003.

A study of the synthesis of the enediyne core structure A and its analogs is presented in chapter 3. The key step is the cyclization step to form a highly strained cyclic 9-membered enediyne molecule. Several model enediynes were synthesized. Among several cyclization methodologies tested on those models, the chromium chloride/nickel chloride mediated cyclization between an aldehyde and an iodoacetylene showed the highest efficiency and consistency. Nevertheless, the technology for the key cyclization step is not fully satisfactory. The Bergman rearrangement of the model enediynes was demonstrated to he fast at room temperature by NMR study. The masked cyclopentene moiety of the part A was synthesized.

ISBN: 0493866280Subjects--Topical Terms:

193634
Chemistry, Organic.

Synthetic study of C-1027-CHR.
LDR:03594nmm _2200301 _450 001 161832
005 20051017073342.5
008 230606s2003 eng d
020 $a 0493866280
035 $a 00148333
035 $a 161832
040 $a UnM $c UnM
100 0 $a Jiang, Yu. $3 226906
245 1 0 $a Synthetic study of C-1027-CHR. $h [electronic resource]
300 $a 265 p.
500 $a Adviser: Martin Semmelhack.
500 $a Source: Dissertation Abstracts International, Volume: 63-10, Section: B, page: 4681.
502 $a Thesis (Ph.D.)--Princeton University, 2003.
520 # $a A study of the synthesis of the enediyne core structure A and its analogs is presented in chapter 3. The key step is the cyclization step to form a highly strained cyclic 9-membered enediyne molecule. Several model enediynes were synthesized. Among several cyclization methodologies tested on those models, the chromium chloride/nickel chloride mediated cyclization between an aldehyde and an iodoacetylene showed the highest efficiency and consistency. Nevertheless, the technology for the key cyclization step is not fully satisfactory. The Bergman rearrangement of the model enediynes was demonstrated to he fast at room temperature by NMR study. The masked cyclopentene moiety of the part A was synthesized.
520 # $a The enediyne natural products are potent cytotoxins which target DNA as a primary biological substrate, causing double or single stranded cleavage. Cycloaromatization of the enediyne unit to a 1,4-arene diradical, which subsequently abstracts hydrogen atoms from the DNA sugar-phosphate backbone is the accepted mechanism by which these compounds render cytotoxicity.
520 # $a The mechanism of activation for C-1027 is still not clear. Several proposed mechanisms of activation for C-1027 are reviewed in chapter 1, which are based both on molecular modeling and incomplete experimental support. Our goal is the synthesis of the natural enediyne C-1027-chr and its functional analogs. A total synthesis would alleviate the problem of the limited supply of the natural product while the designed models offer an opportunity to test possible mechanisms of activation. New enediyne analogies based on a full understanding of the mechanism might improve potency and selectivity in the action of these compounds.
520 # $a The synthesis of the amino sugar B is presented in chapter 4. The key steps include an oxidation of a primary alcohol at C-6 to either aldehyde or ester in the presence of a 4-amino group and double methylation at the C-5 position with an ester at the alpha position. The structure of an unexpected beta-lactam product was established by X-ray diffraction. The structure of the final product was confirmed by comparison NMR spectra data with that of the natural product.
520 # $a The synthesis of the beta-amino acid C is presented in chapter 2. The key steps include the enantioselective Michael addition of an amide anion to an alpha,beta-unsaturated ester and selective debenzylation. The structure of the final compound was confirmed by X-ray crystallography. An efficient coupling reaction between the beta-amino acid and the enediyne core structure A under mild conditions was demonstrated on a model system.
590 $a School code: 0181.
650 # 0 $a Chemistry, Organic. $3 193634
650 # 0 $a Health Sciences, Oncology. $3 226907
710 0 # $a Princeton University. $3 212488
773 0 # $g 63-10B. $t Dissertation Abstracts International
790 $a 0181
790 1 0 $a Semmelhack, Martin, $e advisor
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://libsw.nuk.edu.tw/login?url=http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3067150 $z http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3067150