Synthesis of camptothecin derivatives

Duygu, Arife Neşe
This study presents synthetic studies on camptothecin, a potent antitumor agent in order to improve its stability and solubility without reducing its activity. The study consists of the modification of camptothecin at 20-OH position a new strategy for the targeted and controlled release of the drug and modification at C-7 position to overcome the stability and solubility problems of the free drug. In the first part of the study, the 20-OH functional group of camptothecin was replaced with an unsymmetrical benzoin derivative that is able to release the drug under photolysis at 350 nm. The new prodrugs synthesized possessed higher stability than the camptothecin itself. The in vitro irradiation of the prodrugs at 350 nm was satisfactory without any decomposition of the active substance. The second part of the study comprises the studies on the modification of the 7th position of camptothecin, which is the most suitable position for the modification. In this part of the study, 7-amino and silyl substituted camptothecins were synthesized.Combination of camptothecin with some other drugs such as cisplatin was also investigated in this study. The synthetic efforts showed that the reactions are very promising and the combination studies can be studied as a major subject in the future.


A facile synthesis of (+/-)-mintlactone
Tanyeli, Cihangir; Demir, AS (Informa UK Limited, 1997-01-01)
(+/-)-Mintlactone has been synthesized by applying a novel effective synthetic sequence. 4-Methylcyclohexanone was subjected to acetoxylation with Pb(OAc)(4). Hydrolysis followed by reaction with 2-chloroprogionyl chloride,then treatment with triethyl phosphite and, finally, Horner-Emmons-type intramolecular cyclization afforded (+/-)-Mintlactone.
Synthesis and enzymatic resolution of various cyclopentenoid and cyclohexenoid type compounds
İyigün, Çiğdem; Tanyeli, Cihangir; Department of Chemistry (2005)
The aim of this thesis is to synthesize enantiomerically enriched cyclopentenoid and cyclohexenoid type of compounds with quaternary carbon stereocenters that are the simplest precursors of the complex natural products. The first part of the study involves the preparation of ?'-acetoxy ?'-substituted ?,β-unsaturated cyclic ketones. Methylation, ethylation, benzylation and allylation of cyclohexenone and cyclopentenone derivatives are performed. Then, these compounds are regioselectively oxidized at the ?'-p...
Synthesis of novel chiral N,N-dialkyl substituted 1,4-amino alcohols and applications in asymmetric transformation reactions
Çakır, Esen; Tanyeli, Cihangir; Department of Chemistry (2007)
Amino alcohols are valuable bioactive substances and frequently used as chiral catalyst in various asymmetric transformation reactions. In the synthetic route, the asymmetric synthesis of novel chiral N,N-dialkyl substituted chiral 1,4-amino alcohols are performed starting with meso-anhydride 38. Quinine-mediated desymmetrization of the anhydride with methanol afforded (2S,3R)-cis-monoester 39 with a high enantiomeric excess (up to 98% ee). Chemoselective amidation of hemiester with various N,N-dialkyl subs...
Asymmetric syntheses of various novel chiral ligands with norbornene backbone : the use of chiral catalyst in asymmetric reactions
Elmalı, Olcay; Tanyeli, Cihangir; Department of Chemistry (2005)
The synthetic strategy of this study mainly depends upon the asymmetric desymmetrization of meso norbornene type an anhydride. Asymmetric desymmetrization was achieved by using chinchona alkaloids under kinetically controlled conditions. The resultant mono ester carboxylic acid was epimerized to trans configuration. Subsequent esterification followed by lithium aluminum hydride reduction afforded the first chiral diol ligand with 98 % ee. Transformation of diol to corresponding trans diamine was achieved vi...
Fabrication of gallic acid loaded Hydroxypropyl methylcellulose nanofibers by electrospinning technique as active packaging material
Aydogdu, Ayca; Şümnü, Servet Gülüm; Şahin, Serpil (Elsevier BV, 2019-03-15)
The objective of this study was to encapsulate gallic acid in Hydroxypropyl methylcellulose (HPMC)/poly-ethylene oxide (PEO) blend nanofiber by using electrospinning and examine the usage of nanofibers as active packaging materials. Gallic acid loaded nanofibers showed homogenous morphology. Gallic acid was loaded into nanofibers efficiently and nanofibers showed strong antioxidant activity. As the gallic acid amount increased, the TGA curves had shifted one stage to two stage degradation and degradation te...
Citation Formats
A. N. Duygu, “Synthesis of camptothecin derivatives,” Ph.D. - Doctoral Program, Middle East Technical University, 2005.