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Page Updated on 19th June, 2007

Achievements

 Some Recent Works

 

¨      Basic Research

¨      Designer molecules from sugar amino acids and other scaffolds:

 

¨      Synthesis of Non-natural Peptides with Skeletal and Secondary Structural Diversity from C-linked Carbo-amino acids (Caa)

 

Peptides play an important role in many physiological processes and hence their de novo design has emerged as a valuable tool to critically evaluate the rules of folding and structural stabilization. A variety of secondary structures have been found in b-as well as in g- and d-peptides derived from unnatural amino acids, providing a promising class of peptidomimetics. The presence of additional C-atom in b-amino acids increases the structural diversity, which raises exponentially in g- and d-amino acids. In recent years, we have developed C-linked carbo-b-amino acids (b3-Caas) as a new class of b-amino acids and utilized them to prepare b-peptides with helical diversity and robustness. Though b-amino acids are ubiquitous in nature, b-, g- and d-peptides are not. Hence, new designs were envisaged and peptides were realized with novel helices such as 9-, 9/11-, 11/9-, 12/10- and 11/13-helices form different backbones, while using L-Pro-Gly as turn motif, Helix-Turn-Helix super secondary structure was achieved (Angew. Chem. Int. Ed. 2005, 44, 5878; Angew. Chem. Int. Ed. 2006, 45, 2994; J. Am. Chem. Soc. 2006, 128, 14657; Angew. Chem. Int. Ed. 2006, 45, 8207; J. Org. Chem. 2006, 71, 3976).

 

 

 

¨      Synthesis and structural studies of peptides containing a glucose-derived furanoid sugar amino acid (Gaa)

 

Conformational analysis of peptides containing a glucose-derived furanoid sugar amino acid (Gaa) by detailed NMR and constrained MD studies revealed that the peptides with repeating Gaa-Leu-Val units had conformational signatures very similar to those of linear homooligomers of Gaa (Tetrahedron Lett. 2005, 46, 3065-3070).

 

 

¨      Conformational Analysis of some C2-symmetric Cyclic Peptides Containing Tetrahydrofuran Amino Acids

 

Cyclic oligomers of tetrahydrofuran amino acids – cyclo-(Taa1-Leu-Val)2 (left), cyclo-(Taa2-Leu-Val)2 (middle) and cyclo-(Taa2-Phe-Leu)2 (right) – displayed well-defined intramolecularly hydrogen-bonded structures with distorted ”b-b corner” motifs similar to the tennis ball seam (J. Org. Chem. 2006, 71, 6240-43).

 

 

¨      Crystal Engineering

 

Conformational variability exhibited by mellitic acid anions (MA-n) with organic amine cations: Structures with an abundance of NH…OC hydrogen bonds and a paucity if hydrogen bonds: (J. Chem. Crystallography 2005, 35, 835 – 845).

 

 

The nonplanar disposition of the pyridine ring in 1 made it possible for both pyridines available for salt formation resulting arrangement with alternating layers of P2+ ions and sheets of MA-2 ions.

Surprisingly efforts to obtain a complex from 2 and mellitic acid by mixing aqueous solutions resulted in hard crystals that could be rationalized on the basic prior hydrolysis of 2 to ethylene diamine and the parent ketone.

 

 

¨      Organic Synthesis and Synthesis of Natural Products

 

¨      Total synthesis of stevastelin B3

 

The total synthesis of stevastelin B3 was achieved using, as a key step, a method developed by us for the synthesis of 2-methyl-1,3-diols by Ti(III)-mediated diastereo- and regioselective opening of trisubstituted 2,3-epoxy alcohols, to carry out the stereoselective construction of its propionate-derived fatty acid segment (Tetrahedron Lett. 2003, 44, 4989-4992).

 

 

 

¨      Studies directed towards the synthesis of antascomicin A

 

A stereoselective synthesis of the C1-C21 fragment of the non-immunosuppressive immunophilin-binding natural product, antascomicin A was achieved using, as key steps, highly stereoselective aldol reactions to build the C1-C17 fragment and a Nozaki-Hiyama-Kishi reaction to couple it with the remaining C18-C21 moiety and the C22-C34 fragment of the molecule was prepared using D-quinic acid as the starting material and highly stereoselective aldol reactions were employed, as key steps, to build the remaining stereocentres at C23, C26 and C27 (Tetrahedron Lett. 2006, 47, 4999-5002; ibid 2006, 47, 5003-5005).

 

 

¨      Total synthesis of (-)-clavosolide A

 

The total synthesis of (-)-clavosolide A was achieved employing a radical-mediated route to build the substituted tetrahydropyran unit, a Yamaguchi reaction to construct the diolide aglycon and the Schmidt method for the final glycosidation step (Tetrahedron Lett. 2006, 47, 7435-38).

 

¨      First Total Synthesis and Determination of Absolute Stereochemistry of iso-Cladospolide-B, Cladospolides-B and C

 

The syntheses of iso-cladospolide-B, cladospolide-B and cladospolide-C were achieved with (4S,5S,11S)-configuration. Of the three-stereogenic centres, the C-4/C-5 vic-diol was created by Evans aldol condensation, while the C-11 stereocentre was created by Jacobsen’s method. The synthesis of cladospolides 1-3 defined the absolute stereochemistries of these natural products. (Tetrahedron Lett. 2006, 47, 6531; Tetrahedron Lett. 2006, 47, 6537).

         

 

¨      Stereoselective Syntheses of Pharmaceutically Relevant Chiral Tetrahydrofurans

 

Operationally simple and flexible methods of making chiral tetrahydrofurans of therapeutic relevance were developed (Tetrahedron Asymm.  2005, 16, 1113; Tetrahedron Asymm. 2005, 16, 1125; Tetrahedron Asymm. 2005, 16, 1135).

 

 

¨      First Total Synthesis of Xylobovide From ‘Diacetone Glucose’ and Determination of the Absolute Stereochemistry

 

The first total synthesis by an intramolecular radical cyclisation protocol on a carbohydrate derived 5-hexynyl-system and determination of the absolute stereochemistry of xylobovide was achieved (Tetrahedron Lett. 2005, 46, 1307).

 

 

¨      An Efficient ZrCl4 Catalysed One-pot Solvent Free Protocol for the Synthesis of 4-Substituted Coumarins

 

A versatile and efficient route to 4-substituted coumarins via a Pechmann reaction using ZrCl4 as the catalyst (10 mol%) is described. This method provides several advantages over alternative procedures such as mild, solvent-free conditions at ambient temperature, and direct isolation of the products in high yields. (Tetrahedron Lett. 2005, 46, 6119)

 

¨      Synthesis of trans-1,8,12,13-tetraoxadispiro[4.1.4.2]-tridecanes-a new class of peroxides

    

Trans-1,8,12,13-tetraoxadispiro[4.1.4.2]tridecanes are hybrid structures of spiro ketals and peroxides which are important components of many bio active compounds. These new class of peroxides have been synthesized using Birch reduction of aromatic compounds followed by ozonalysis and acid catalysed cyclisation (Tetrahedron Letters 2006, 47, 771-774).

 

 

¨      Chiron approach for the Synthesis of (1S,2R,5R,7S)-2-hydroxy-exo-brevicomin  

 

(1S,2R,5R,7S)-2-Hydroxy-exo-brevicomin was synthesized from 1,2;5,6-di-isopropylidine-D-glucose in seven steps. The key reaction in the synthesis was the formation of bicyclic ketal under acid mediated acetal exchange of 1,3-acetonide of D-glucose derivative (Tetrahedron: Asym.  2006, 17, 819-821).

 

 

¨      Stereoselective Synthesis of bis-hydroxy-tetrahydrofurans using cross metathesis

 

A short asymmetric approach for the synthesis of bis-tetrahydrofuran unit of various annonaceous acetogenins was developed. The key steps of the synthesis were cross metathesis and Sharpless asymmetric dihydroxylation reactions (Tetrahedron Lett. 2006, 47, 3401-3403).

 

 

¨      Stereoselective approach to pentenocins using RCM: synthesis of 6-epi-pentenocin B                                   

 

Stereoselective synthesis of 6-epi-pentenocin B was achieved using stereoselective Grignard reaction and ring closing metathesis (RCM) as the key steps (Tetrahedron Lett. 2006, 47, 441-443).

 

 

¨      Stereocontrolled Copper Iodide Catalyzed Phosphorus-Carbon Bond Formation: An Efficient Synthesis of Scalemic Tertiary Phosphine-Boranes

 

We developed a method for the formation of P-C bond virtually using non-basic conditions with sub-stoichiometric amount of copper iodide as a catalyst. A series of compounds were subjected to coupling reaction and the corresponding products were obtained in high yields with retention of configuration (Synlett 2006, 1122-1124).

 

 

¨      Studies directed towards the total synthesis of familiy of Belactosin molecules: A novel anti tumour antibiotic

 

Belactosin, a metabolite of streptomyces and a potential drug for antitumour activity, was synthesized (J. Org. Chem. 2006, 71, 337-340).

 

 

¨      Total synthesis of (-)-microcarpalide from D-mannitol

    

The total synthesis of the actin-targeting metabolite (-)-microcarpalide was achieved using ring-closing metathesis of a dienicm ester as the key step (Tetrahedron Lett. 2005, 46, 5479-5481).

 

 

¨      A general strategy for the stereoselective synthesis of L-1-deoxyallonojirimycin and D-1-deoxygulonojirimycin

 

A general strategy for the synthesis of deoxyazasugars from D-glucose was developed using ring-closing metathesis and stereoselective dihydroxylation reactions as key steps. (Tetrahedron Lett. 2006, 47, 6041-6044)

 

 

¨      Daistereoselective Passerini reactions using TosMIC as the isonitrile component

 

p-Toluenesulfonylmethyl isocyanide (TosMIC) was used for the first time as the isonitrile component in a diastereoselective Passerini reaction with sugar-derived aldehydes to afford products in moderate to good yields (40-90%) and selectivities (30-90% de’s) (Tetrahedron Lett. 2006, 47, 5977-5980; Synlett 2007, 83-86).

 

                    

 

¨      Diversely substituted sugar-linked α,β-unsaturated γ-lactones from sugar-derived Baylis-Hillman adducts via a RCM

 

A versatile protocol for the production of sugar-linked α,β-unsaturated γ-lactones with stereochemical and functional group diversity is described starting from sugar-derived Baylis-Hillman adducts via ring closing metathesis (Tetrahedron: Asymm. 2005, 16, 2691-2703; Synlett 2006, 595-599; J. Comb. Chem. 2007, 9, 62-69).

 

¨      Stereoselective total synthesis of (-)-decarestrictine D from L-malic acid.

 

A convergent stereoselective total synthesis of (-)-decarestrictin D from L-malic acid was reported (Tetrahedron Lett. 2006, 47, 7473-7476).                                   

 

 

¨      Stereoselective total synthesis of (+)-cardiobutanolide and (+)-3-epi-cardiobutanolide from diacetone D-glucose

 

A chiron approach, starting with 3-O-benzyl-1,2-O-isopropylidene-α-D-xylo-pentodialdo,14-furanose utilizing a Grignard reaction, Mitsunobu stereoinversion, ethyl diazoacetate addition, and selective reduction of the ketone, was employed for the total synthesis of (+)-cardiobutanolide (Tetrahedron Lett. 2006, 47, 4627-4630).

       

                            

 

 Some important publications

 

  1. J. Am. Chem. Soc. 2006, 128, 14657-14668 .
  2. Angew. Chem. Int. Ed.  2006, 45, 2944-2947.
  3. J. Am. Chem. Soc. 2005, 127, 9664-9665
  4. J. Am. Chem. Soc. 2004, 126, 13586-13587.
  5. Chem. Commun. 2004, 2580-2581.
  6. Angew. Chem. Int. Ed.  2004, 43, 3961-3497.
  7. J. Am. Chem. Soc. 2003, 125, 13670-13671.
  8. J. Org. Chem. 2002, 67, 2093-2100.
  9. J. Org. Chem. 2000, 65, 6441-6457.
  10. J. Am. Chem. Soc. 1998, 120, 12962-12963.