IISc Logo    Title

etd AT Indian Institute of Science >
Division of Chemical Sciences >
Organic Chemistry (orgchem) >

Please use this identifier to cite or link to this item: http://hdl.handle.net/2005/931

Title: Studies Of NIS Mediated Cyclopropane Ring Opening Reactions In Carbohydrate Chemistry
Authors: Haveli, Shrutisagar D
Advisors: Chandrasekaran, S
Keywords: Carbohydrate Chemistry
Cyclopropane Ring
Perhydrofuro Pyrans - Synthesis
Perhydrofuro/Pyrano Butyrolactones - Synthesis
Amino Acid Nucleosides - Synthesis
Spiro-Perhydrofuropyrans - Synthesis
1, 2- Cyclopropane
NIS Mediated Ring
Submitted Date: Mar-2009
Series/Report no.: G22931
Abstract: The thesis entitled ‘Studies of NIS Mediated Cyclopropane Ring Opening Reactions in Carbohydrate Chemistry’ is divided into four chapters. Chapter 1: Section 1: Efficient Synthesis of Fused Perhydrofuro[2,3-b]pyrans (and furans) by Ring Opening of 1,2-Cyclopropanated Sugar Derivatives. In this section a general and efficient methodology for the synthesis of carbohydrate derived perhydrofuro[2,3-b]pyrans (and furans) from the corresponding 1,2-cyclopropane carboxylates has been discussed. A wide range of linear-fused perhydrofuro[2,3-b]pyran or furan ring systems are encountered in a number of biologically active natural products. A few approaches are available for the construction of this kind of fused motifs which involve harsh reaction conditions and lengthy reaction sequence. The methodology utilizes the potential ability of cyclopropanated sugars to undergo N-iodosuccinimide (NIS) mediated electrophilic ring opening assisted by the pyran ring oxygen followed by intramolecular trapping of oxonium intermediate to generate the furan ring system. Cyclopropantion of tribenzyl glucal using methyl diazoacetate and catalytic amount of dirhodiumtetracetate furnished corresponding exo-1,2-cyclopropane carboxylate exclusively. To generate a nucleophile, cyclopropane carboxylate ester was reduced to the corresponding alcohol which upon treatment with NIS in CH3CN underwent ring opening followed by intramolecular ring closure to give the corresponding perhydro[2,3-b]furopyran along with an oxidized product. After various modifications we found that using CH2Cl2 as a solvent gave the expected perhydrofuropyran as the sole product in good yield (Scheme I). The stereochemistry of the product was established on the basis of 1H-1H NOESY experiment. There are many natural products that contain the perhydrofuro[2,3-b]furyl glycal core such as clerodin, jodrelline B and caryoptin, which show insect anti-feedant properties. With this in mind, the methodology has been successfully extended to the cyclopropanated tetrahydrofuran derivatives resulting in the synthesis of furofuryl glycal moiety (Scheme II). Scheme II Chapter 1: Section 2: Synthesis of Carbohydrate Derived Fused Perhydrofuro/pyrano[2,3-b]-γ-butyrolactones. In this section a general and efficient methodology for the synthesis of carbohydrate derived perhydrofuro/pyrano[2,3-b]-γ-butyrolactones has been discussed. The fusion of the γ-butyrolactone onto a substituted tetrahydrofuran/pyran ring makes a distinctive class natural diterpenoids. Representative members of this family include the marine diterpenoids norrisilide and miniolutelide A. In this chapter we describe a neutral and general method for the construction of perhydrofuro/pyrano[2,3-b]-γ-butyrolactones by NIS mediated ring opening of carbohydrate derived 1,2-cyclopropane carboxylic acids (Scheme III). Scheme III The present strategy is complementary to the existing methods and it is useful since it incorporates an additional chiral center in the molecule under milder conditions, which can be used for further transformations. Chapter 2: Ring Opening of Activated Cyclopropanes with NIS/NaN3: One-pot Synthesis of C-1 Linked Pseudo Disaccharides. Ring opening reactions of activated cyclopropanes have been widely used in organic synthesis. But they are restricted to only selected nucleophiles such as alcohol/ water, as most of the ring opening reactions need acidic activation. This chapter deals with studies of reactivity of various activated cyclopropanes with NIS as a neutral activator and sodium azide as a source of nitrogen nucleophile (Scheme IV). Scheme IV We have clearly demonstrated not only the importance of the donor-acceptor feature in the cyclopropanes in the electrophilic ring opening reaction, but also the selectivity in its functionality. Scheme V This methodology has been successfully utilized in a one-pot synthesis of C-1 linked pseudo-disaccharides from carbohydrate derived 1,2-cyclopropane carboxylates (Scheme V). Chapter 3: Synthesis of Unnatural C-2 Amino Acid Nucleosides Using NIS Mediated Ring Opening of 1,2-Cyclopropane Carboxylated Sugar Derivatives. In this chapter, we have efficiently demonstrated the utility of NIS mediated regioselective ring opening of carbohydrate derived donor-acceptor cyclopropanes for the synthesis of C-2 amino acid nucleosides. This leads to a new class of analogs of peptidyl nucleosides (Scheme VI). Scheme VI One of the advantageous factors is the attachment of nucleobase as well as generation of amino acid precursor in the same reaction which avoids lengthy reaction sequence. We have also shown the synthetic utility of our methodology to pyrimidine based furanosyl C-2 amino acid nucleosides which are of interest, since polyoxins having similar structural core exhibit antifungal activity (Scheme VII). Chapter 4: Attempts Towards the Synthesis of Carbohydrate Derived Spiro-perhydrofuropyrans Using NIS Mediated Cyclopropane Ring Opening Reaction. In this chapter we present various attempts to synthesize spiro-perhydrofuropyran/furans by ring opening of spiro-cylopropane derivatives and attempts towards stereoselective synthesis of spiro-cyclopropane carboxylates. Spiroacetal can be synthesized from the corresponding exo-cyclopropyl methanol, which can be obtained from the corresponding exo- cyclopropane carboxylate. The cyclopropyl carboxylate can be obtained from an exo- vinyl ether. Cyclopropanation of carbohydrate derived exo-glycal failed to give any selectivity under a variety of reaction conditions (Scheme VIII). Carbohydrate derived C1-unsaturated ester on cyclopropanation reaction using standard conditions (Pd(OAc)2/CH2N2) was found to be inert. The reaction under Simmons-Smith cyclopropanation conditions also gave similar results. Reduction of the ester part of the molecule to the corresponding alcohol was found to be helpful in the Simmon-Smith cyclopropanation reaction (CH2I2, Et2Zn) to obtain the corresponding exo-cyclopropane, but disappointingly without any selectivity (Scheme IX). In order to get exo-cyclopropane carboxylate with high stereoselectivity, we decided to use one of the hydroxyl group present in the molecule, as a chiral auxiliary. All the established methods for the diazoester formation failed to attach diazo ester at C-4 position (Scheme X). Scheme X (For structural formula pl see the pdf file)
URI: http://etd.iisc.ernet.in/handle/2005/931
Appears in Collections:Organic Chemistry (orgchem)

Files in This Item:

File Description SizeFormat
G22931.pdf5.64 MBAdobe PDFView/Open

Items in etd@IISc are protected by copyright, with all rights reserved, unless otherwise indicated.


etd@IISc is a joint service of SERC & IISc Library ||
|| Powered by DSpace || Compliant to OAI-PMH V 2.0 and ETD-MS V 1.01