The thesis entitled "Synthesis of Novel Chalcogenides using Acyloxyphosphonium Intermediates and Doubly Activated Cyclopropanes" is divided into six chapters. Chapter 1: Part 1: Synthesis of thioesters from carboxylic acids and alkyl halides using benzyltriethylammonium tetrathiomolybdate In this chapter, we describe the synthesis of thioesters from carboxylic acids and alkyl halides. Aryl carboxylic acids are first activated using PPh3 and NBS to form the corresponding acyloxy phosphonium intermediates which then on further reaction with reagent, 1generate thioaroylate ions in situ. These thioaroylates on further reaction with various electrophiles such as alkyl halides / dihalides in the same pot gives the corresponding functionalized thioesters. This methodology was then extended to carbohydrate based thioesters as they are important synthetic intermediates in various transformations and also they could be deprotected later to synthetically more valuable thiols. For this study, we took 1,2,3,4tetra-O-acetyl-β-D-glucopyranuronic acid which on treatment with PPh3,NBS, reagent, 1 and I-bromo propane (CHCl3, 28°C, 2h) afforded the corresponding thioester in 55% yield. An intramolecular version of the reaction was then performed on a compound containing both anomeric bromide and carboxylic acid functionality. This was achieved by treating tetra acetyl glucuronic acid, with HBr/AcOH to form α-D-bromo-glucopyranuronic acid which on further treatment with PPh3, NBS and reagent, 1 gave the corresponding bicyclic thiolactone in 55% yield. Chapter 1: Part 2: Synthesis of Thioesters by Simultaneous Activation of Carboxylic Acids and Alcohols using PPh3/NBS In this chapter, we have shown the synthesis of thioester from carboxylic acids and alcohols. Both carboxylic acids and alcohols are first activated using PPh3 and NBS to form the corresponding phosphonium salts. Reagent, 1 then reacts selectively with acyloxyphosphonium intermediates to generate thioaroylate ions in situ which then react either with alkoxy phosphonium salts or the corresponding alkyl bromide to give thioesters in good yield. The same methodology was then used for a one pot conversion of N-Boc serine ester to s-protected cysteine using reagent 1 as the key sulfur transfer reagent. Chapter 2: Part 1: Tetrathiomolybdate mediated Michael addition of thioaroylates generated from acyloxyphosphonium salts In this chapter, we have reported an easy and alternative protocol for the Michael addition of thioacids to various Michael acceptors. Acyloxyphosphonium salts and tetrathiomolybdate reacts to generate thioaroylate ions which then undergo Michael additionto givethe corresponding Michael adducts. This methodology was then extended for the synthesis carbohydrate based thiolactone by an intramolecular Michael addition reaction to show the applicability of the methodology. Chapter 2: Part 2: Regioselective and chemoselective ring opening of aziridines and epoxides using thioaroylate ions In this chapter, we have demonstrated nucleophilic ring opening of Aziridines and epoxides using thioaroylate ions generated from acyloxyphosphonium salts and tetrathiomolybdate as a sulfur transfer reagent. We have also demonstrated chemoselective ring opening of azirdines in the presence of an epoxide and tosylate to show the novelty of our method. Chapter 3: Synthesis of bromo esters and bromo thioesters by ring opening of cyclic ethers and thiiranes via acyloxyphosphonium intermediates In this chapter, we report the synthesis of bromo esters and thioesters by the ring opening of epoxides, tetrahydrofuran, and thiiranes with bromide ion to form the corresponding bromo alcohols and thiols followed by the nucleophilic displacement of triphenylphosphine oxide from acyloxyphosphonium salts. At first THF and epoxides were subjected for the ring opening reactions to give the corresponding bromo esters. The methodology was then extended to thiiranes to synthesis bromo thioesters in good to moderate yield. Chapter 4: Synthesis of doubly activated cyclopropranes and their applications to the synthesis of dihydrothiophenes and thiophenes In this chapter we discuss the synthesis and ring opening of doubly activated cyc1opropanes using tetrathiomolybdate and their applications towards the formation of dihydrothiophenes and other bioactive molecules. At first, we synthesized a number of doubly activated cyc1opropanes from dimethyl-α-arylsulfonium bromide,24 a protocol developed by Chow and others. With the doubly activated cyclopropanes in hand, we then attempted the ring opening of cyclopropanes containing a cyano group with tetrathiomolybdate to give the corresponding dihydrothiophene derivatives. Also we have used our methodology for the synthesis of HIV-1 reverse transcriptase inhibitor Chapter 5: Synthesis of unsymmetrical sulfide and disulfide derivatives via ring opening of doubly activated cyclopropanes Here, we describe the synthesis of various monosulfides and mixed disulfides by doubly activated cyclopropane ring opening mediated by tetrathiomolybdate in one pot. Tetrathiomolybdate is known for the reduction of disulfides while diaryl disulfides gives monosulfide, dialkyl disulfides give mixed disulfides with the corresponding doubly activated cyclopropane. Thus diaryl disulfide cleaves readily as the resultant thiolate ion is stable and opens the cyclopropane ring to give a monosulfide. Dibenzyl disulfide on the other hand being less reactive gave a mixed disulfide instead of a monosulfide. We also extended this ring opening reactions for the synthesis of symmetrical disulfides Using tetrathiomolybdate as the key sulfur transfer reagent. Chapter 6: A mild protocol for the nucleophilic ring opening of doubly activated cyclopropanes using selenolates generated in situ Nucleophilic ring opening of doubly activated cyc1opropanes with selenolate ions generated by the reduction of diselenides using NaB14 is discussed in this part of the work. A variety of doubly activated cyc1opropanes have been tested for this reaction giving the corresponding selenium compounds in good yield. This methodology was then extended to other diselenides using nitroester cyclopropane as standard and also to other substituted nitroester cyclopropanes using diphenyl diselenide as standard. This methodology was also then extended to the synthesis of homoselenocysteines by the reduction of nitro group using Sn/HCI for the reduction. (For structural formula pl refer the hard copy)

People experience the irritating tearing and burning sensation of lachrymatory factor (LF, propanthial S-oxide) when cutting or chopping onion bulbs. LF is produced by lachrymatory factor synthase (LFS) specifically from 1-propenyl sulfenic acid, a breakdown product of trans-1-propenyl-L-cysteine sulfoxide (1-PRENCSO) by alliinase. This thesis describes strategies to produce a tearless onion by using RNA interference (RNAi) silencing. To determine whether a gene silencing cassette can silence lfs gene transcripts from onion (Allium cepa L.), a crop recalcitrant to genetic transformation, a gene silencing assessment system was developed by using a model plant as a host for the gene of interest. Tobacco (Nicotiana tabacum) plants transgenic for LFS enzyme activity from onion were first produced by introducing a CaMV 35S-onion-lfs gene construct. These plants were then subjected to a second transformation with an RNAi construct directed against the lfs gene sequence. LFS enzyme activity assay showed that the transgenic plants, containing both the lfs gene and the RNAi construct, had significantly reduced LFS activity. This observation was supported by Western analysis for the LFS protein and further validated by quantitative RT-PCR analysis that demonstrated a significant reduction in the lfs transcript level in the dual transformants. This work demonstrated that the RNAi construct is a suitable candidate for the development of a tearless onion. This model plant RNAi system has wide reaching applications for assessment and targeting of plant secondary pathway genes, from poorly studied or recalcitrant plant species, that are important in pharmacological, food and process industries. The functional RNAi vector identified in the model system was transformed into onion. Endogenous lfs transcript levels were successfully reduced by up to 43-fold in six transgenic lines. In consequence, LFS enzyme activity was decreased by up to 1573-fold and this observation was supported by Western analysis for the LFS protein. Furthermore, the production of the deterrent LF upon tissue disruption was reduced up to 67-fold. Subjective olfactory assessment of silenced lines indicated that the pungent odour given off by the leaf and bulb material was much reduced compared with that of non-transgenic counterparts, and that this was replaced by a sweeter milder onion odour. A novel colorimetric assay demonstrated that this silencing had shifted the 1-PRENCSO breakdown pathway so that by reducing LFS protein, more 1-propenyl sulfenic acid was converted into di-1-propenyl thiosulfinate. A consequence of the raised thiosulfinates levels was a marked increase in the downstream production of a non-enzymatically produced zwiebelane isomer that has never previously been identified, and other volatile compounds, di-1-propenyl disulfides and 2-mercapto-3,4-dimethyl-2,3-dihydrothiophenes, which had previously been reported either in small amounts or had not been detected in onions. These raised volatile sulfur compounds provide an explanation for the unique flavour notes of the LF reduced onion and are predicted to have health benefits akin to those found in garlic. These results demonstrated that silencing of LFS enzyme activity by introducing an RNAi construct directed against the lfs gene sequence simultaneously reduced levels of the deterrent LF and increased the desirable thiosulfinates in onions.