http://hdl.handle.net/2005/14 2013-05-21T15:08:35Z http://hdl.handle.net/2005/1938 Title: Enantiospecific Synthesis Of Bioactive Styryllactones Authors: Dhaware, Madhuri Gautam Abstract: The thesis entitled “Enantiospecific synthesis of bio-active stryllactones” comprise an introduction about stryllactone and two chapters describes the synthesis of stryllactones. Trees of the genus Goniothalamus of the plant family Annonaceae in South East Asia has been known for a long time for their proven as folkloric medicine. Stryryllactones were found to exhibit moderate to significant biological activity including antitumour, antifungal as well as antibiotic properties. Because of their unique and intriguing structures and the activity associated much effort has been centered on the development of methodology for the synthesis of these compounds. The structures and relative configurations of these compounds were determined either by X-ray crystallography or by extensive NMR spectral analysis and by mass spectroscopic techniques. The research group of McLaughlin isolated and characterized a series of styryllactones, possessing significant to marginal cytotoxic activity against human tumor cell lines. The structures and relative configurations of these compounds were determined either by X-ray crystallography or by extensive NMR spectral analysis. Classification of these styryllactones is based on the structural characteristics of the six different skeletons as shown in Figure 1. Figure 1:features styryllactone the genus In this thesis, enantioselective total synthesis of styryllactones ()-9-deoxygoniopypyrone 1, ()-goniopypyrone 2, ()-7-epi-goniofufurone 3, ()-7-epigoniodiol 4 and the putative structure of ()-etharvendiol 5 is presented. a) Total synthesis of ()-9-deoxygoniopypyrone, ()-goniopypyrone, ()-7-epigoniofufurone and ()-7-epi-goniodiol: Synthesis of the styrylalctones is relied on elaboration of the trihydroxy ester 11 derived from tartaric acid. Appropriate protection of the hydroxy groups and further modifications of the ester functionality (which can be transformed into the corresponding alcohol or aldehyde) is planned for the synthesis of the styryllactones 1-5. Accordingly, the bis-dimethylamide 9 derived from D-()-tartaric acid, was transformed to the -hydroxy amide 10 using a combination of Grignard reagent addition followed by reduction of the resultant ketone. Acid mediated deprotection of the acetonide with concomitant hydrolysis of the amide to the ester is accomplished in one pot by treating 10 with p-TSA in benzene/MeOH mixture Treatment of the trihydroxy ester with 2,2-dimethoxy propane in presence of p-TSA afforded the hydroxy ester 12 which was elaborated to the styrylalctones 9deoxygoniopypyrone, 7-epi-goniodiol, 7-epi-goniofufurone and goniopypyrone (Scheme-2). (Part of this work is published: Prasad, K. R.; Dhaware, M.G. Synlett. 2007, 11121114.; Prasad, K.R.; Dhaware, M.G. Synthesis 2007, 3697) b) Stereoselective synthesis of the putative structure of (+)-etharvendiol: In 1997, Bermejo et al isolated the styryl pyrone etharvendiol 5 from the ethanolic extract of stem bark from Goniothalamus arvensis. Hitherto, no synthesis of etharvendiol is reported in the literature. In this section, approach towards the synthesis of putative structure of etharvendiol will be discussed. Synthesis of etharvendiol 5 is anticipated by the elaboration of masked tetrol 15, comprising an alkene tether and four contiguous hydroxy groups installed with definite configuration. It is relied on exploiting the hydroxy directed lactonization via the oxidation of alkene in 15, and subsequent elaboration to 7. Bis-dimethylamide 9, derived from D-()-tartaric acid was identified as the suitable precursor for the synthesis of 15. Synthesis of masked tetrol 15 is accomplished from 9 involving a combination of selective Grignard additions and stereoselective reduction (Scheme 3). (For structural formula pl see the pdf file) 2013-02-24T18:30:00Z http://hdl.handle.net/2005/1969 Title: Enantiospecific Synthesis Of Tetraquinane Diterpenes Crinipellins Authors: Gowri, V Abstract: Among Nature's creation, terpenoids are more versatile and exciting compounds, and provide fertile ground for developing and testing new synthetic strategies because of their phenomenal structural diversity. The thesis entitled “Enantiospecific Synthesis of Tetraquinane Diterpenes Crinipellins” describes the first enantiospecific synthesis of norcrinipellin and crinipellins, and the tricyclic core structure of tricycloillicinone, ialibinones, and takaneones. In the thesis, the compounds are sequentially numbered (bold) and references are marked sequentially as superscripts and listed at the end of the thesis. All the spectra included in the thesis were obtained by xeroxing the original NMR spectra. Crinipellins, the first group of natural products to contain a tetraquinane carbon framework, were isolated in 1985 by the research groups of Steglich and Anke from the submerged cultures of the basidiomycete Crinipellis stipitaria. Recently, In 2010, Shen and Li also reported the isolation of four new crinipellins from the Crinipellis stipitaria 113. In the present thesis, first enantiospecific synthesis of norcrinipellin and crinipellins has been described. To begin with, (S)-campholenaldehyde was transformed into the (1R,5R)-7,8,8-trimethylbicyclo[3.3.0]oct-6-en-3-one employing an intramolecular rhodium carbenoid insertion of a diazoketone, which was then transformed into the methyl (1R,2S,6R,8S,10R)-10-methoxy-2-methyl-5-oxotricyclo[6.3.0.02,6]undecane-4-carboxylate via rhodium carbenoid promoted activation of a tertiary methyl group to generate the cis, anti, cis-linear triquinane. The triquinane obtained was then transformed into ethyl 4-[(1R,2S,6S,8S,10R)-10-methoxy-2,5dimethyl-3-oxotricyclo[6.3.0.02,6]undec-4-ene-6-yl]butanoate by a sequence of reactions including an alkylative 1,3-enone transposition, which on intramolecular Michael addition reaction followed by DBU mediated equilibration generated a 5:4 mixture of ethyl (1S,3S,5R,7R,8S,11S,12R) and (1S,3S,5R,7R,8S,11S,12S)-5-methoxy8,11-dimethyl-9-oxotetracyclo[6.6.0.01,11.03,7]tetradecane-12-carboxylates, which were transformed into (12R) and (12S)-15-hydroxy-5-methoxy-20-norcrinipellin-9-ones and (12S) and (12R)-5-methoxy-20-norcrinipell-15-en-9-ones. The methodology has been further modified and extended for the first enantiospecific synthesis of (12R) and (12S) 15-hydroxy-5-(methoxymethoxy)crinipellin-9-ones In 1995, Fukuyama and coworkers reported the isolation of tricycloillicinone from Illicium tashiroi, containing an interesting 3,4,4-trimethyltricyclo[5.3.1.01,5]undecane system. This tricyclic structure was also present in two groups of acylphloroglucinoid natural products, ialibinones and takaneones. An enantiospecific synthesis of the tricyclic core structure of tricycloillicinone, ialibinones, and takaneones have been accomplished starting from (S)-campholenaldehyde employing a transannular RCM reaction as the key step, (S)-Campholenaldehyde was converted into methyl (5R)-6,6,7-trimethyl-3-oxobicyclo[3.3.0]octa-1,7-diene-2-carboxylate via the methyl (1R,5R)-6,6,7-trimethyl-3-oxobicyclo[3.3.0]oct-7-ene-2-carboxylate, which was then transformed into (1R,3S,5S)-3-allyl-7,8,8-trimethyl-5-vinylbicyclo[3.3.0]oct6-en-3-ol containing the vinyl and allyl groups at C-1 and C-3 carbons syn to each other. Transannular RCM reaction of the hydroxy diene led to the tricyclic core structure of tricycloillicinone. Further elaboration of the side chain at C-3 position led to the tricyclic core structure of ialibinones, and takaneones. 2013-04-14T18:30:00Z http://hdl.handle.net/2005/1935 Title: Exo- And Endo-Receptor Properties Of Poly(Alkyl Aryl Ether) Dendrimers. Studies Of Multivalent Organometallic Catalysis And Molecular Container Properties Authors: Natarajan, B 2013-02-24T18:30:00Z http://hdl.handle.net/2005/1925 Title: Synthetic And Mechanistic Studies In Oxime And Amide Chemistry Authors: Veera Reddy, Yatham Abstract: The thesis entitled “Synthetic and Mechanistic Studies in Oxime and Amide Chemistry” consists of two chapters. Chapter 1 contains 3 parts, dealing with the Beckmann rearrangement under solvent free conditions, Mitsunobu conditions, and with catalytic succinic anhydride-ZnCl2. Chapter 2 deals with bond length and reactivity studies with several oxime esters. CHAPTER 1 Part 1: This describes studies aimed at the development of the Beckmann rearrangement in the solid state using phenylboronic acid. The adsorption of ketoximes on a mixture of phenylboronic acid and neutral alumina followed by heating >120 °C, afforded the expected amides, although with competing hydrolysis to corresponding ketones. It appeared that phenylboronic acid was being converted under the reaction conditions to triphenyl boroxine, which was presumably the active species effecting the Beckmann rearrangement. This was experimentally confirmed when the amide products were obtained in good yields when the reaction was performed with triphenyl boroxine. Part 2: This describes the Beckmann rearrangement under Mitsunobu conditions. Triphenyl phosphine and diethyl azodicarboxylate can react with various oximes to produce corresponding amides. Part 3: This describes the Beckmann rearrangement of oximes to amides by a combination of succinic anhydride and zinc chloride as catalyst. Zinc chloride can activate succinic anhydride, the activated succinic anhydride then reacting with the oximes. This forms the oxime ester of succinic acid, which undergoes the Beckmann rearrangement as shown. CHAPTER 2: This describes bond length and reactivity studies with several oxime esters. It was of interest to obtain a correlation between bond length and reactivity in ketoxime derivatives which are known to undergo the Beckmann rearrangement. Towards this end the crystal structures of a variety of oxime esters have been determined. The results indicate that the alkyl group anti to the oxime hydroxyl group is pre-disposed towards migration onto the nitrogen center. (pl refer the thesis for structural formula) 2013-02-13T18:30:00Z