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Synthesis studies on enediyne toxins

Record Type:	Electronic resources : Monograph/item
Title/Author:	Synthesis studies on enediyne toxins
Author:	Wu, Lingyun.
Description:	286 p.
Notes:	Adviser: Martin F. Semmelhack.
Notes:	Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0230.
Contained By:	Dissertation Abstracts International65-01B.
Subject:	Chemistry, Organic.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3120476
ISBN:	0496678426

Synthesis studies on enediyne toxins
Wu, Lingyun.

Synthesis studies on enediyne toxins [electronic resource] - 286 p.

Adviser: Martin F. Semmelhack.

Thesis (Ph.D.)--Princeton University, 2004.

For the purpose of better understanding of the activation mechanism of the labile enediyne c-1027-chr, a general method towards the synthesis of nine-membered enediynes which are stabilized with easily removable protection groups, such as cobalt complexation, is highly desirable. New enediyne precursors with alkyne-cobalt coordination or latent ene units have been designed and successfully synthesized. Unfortunately, the final ring closure reactions failed in these systems. The instability of the cobalt coordination under strongly basic conditions in addition to the intrinsic difficulty of the ring cyclization reaction to make the nine-membered enediynes have thwarted these efforts.

ISBN: 0496678426Subjects--Topical Terms:

193634
Chemistry, Organic.

Synthesis studies on enediyne toxins
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500 $a Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0230.
502 $a Thesis (Ph.D.)--Princeton University, 2004.
520 # $a For the purpose of better understanding of the activation mechanism of the labile enediyne c-1027-chr, a general method towards the synthesis of nine-membered enediynes which are stabilized with easily removable protection groups, such as cobalt complexation, is highly desirable. New enediyne precursors with alkyne-cobalt coordination or latent ene units have been designed and successfully synthesized. Unfortunately, the final ring closure reactions failed in these systems. The instability of the cobalt coordination under strongly basic conditions in addition to the intrinsic difficulty of the ring cyclization reaction to make the nine-membered enediynes have thwarted these efforts.
520 # $a The design and synthesis of functional analogs of natural enediynes with increased selectivity is an important goal in enediyne research. Selectivity improvement may be achieved via selective activation by specially designed triggers. A conformationally controlled trigger mechanism is proposed based on DFT calculations. The [7.3.1] enediyne with a boat cyclohexane ring should be much more stable than the chair conformer by these calculations. An example of this framework restricted in the boat conformation with a 1,3-lactone ring was evaluated by DFT calculations and found to be a promising candidate. The framework was synthesized through a Cr(II)-promoted cyclization, and showed the predicted high stability even at 74°C. Lactone ring-opening by basic hydrolysis or DIBALH reduction led to an enediyne which cannot be isolated using routine purification methods. The in situ generated ring-opened enediyne was evaluated by UV to have a very short half-lifetime (ca. 42 min) at 25°C. The experimental results support the assumption that the cyclohexane ring conformation is critical for the reactivity of [7.3.1] enediynes. With both theoretical calculation and experimental methods, a new trigger mechanism by conformational control is established for the [7.3.1] enediynes.
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