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      Synthesis of higher carbohydrates and iminosugars on dioxanone scaffold

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      Nagarjuna_Palyam_2010.pdf (2.602Mb)
      Date
      2010-06-28
      Author
      Palyam, Nagarjuna
      Type
      Thesis
      Degree Level
      Doctoral
      Metadata
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      Abstract
      Dioxanones (1) are ketal- or acetal protected forms of 1,3-dihydroxyacetone (DHA). The thesis presents the stereoselective aldol transformations of dioxanones and applications to the synthesis of natural and higher carbohydrates listed in Scheme 1. The field of organocatalysis has recently gained much popularity among the chemical research community. In our group, a set of conditions are developed to perform stereoselective aldol reactions on dioxanone substrate. Cs-symmetrical dioxanones have superior diasteroselectivities than C2v-symmetrical dioxanones (de up to 88% from 34%) and presence of mild Lewis acid (LiCl) or Brønsted acid additives (PyPTS) enhance the enantioselectivity into synthetically useful ranges (from 60 up to 96% ee). The first aldol addition of dioxanone (1) to desired aldehydes (possessing masked carbonyl functionality), followed by reduction of the corresponding aldol adduct and upon unmasking the aldehyde functionality (i.e dithiane or dimethoxy acetal hydrolysis) resulted in furanose (II) and pyranose (III) forms of D-ribose. A new protocol was developed for the synthesis of biologically important deoxyiminosugars such as L-1-deoxymannojirimycin (DMJ, IV), L-1-deoxyidonojirimycin (DIJ, V) and N-isopropyl DIJ (IV) from readily available dioxanone (1) precursor. The key steps include diastereoselective proline-catalyzed syn-aldol transformation and a reductive amination / cyclization. D-glycero-D-manno-2-octulose (VII), a higher-carbon sugar isolated from opium poppies has been synthesized in enantiomerically pure form. The short synthetic sequence involved two proline-catalyzed aldol addition reactions of dioxanone (1) to appropriate aldehydes. Here, we developed a complete dioxanone methodology towards the higher monosaccharide in a stereocontrolled fashion. The enantioselective stereodivergent first total synthesis of DD- and LL-glycero-β-alloheptopyranose (IX, ent-IX) was accomplished from readily available non-chiral starting materials. The short synthetic sequence involves enamine and enolate mediated aldol reactions at α and α' positions of dioxanone (1) hence demonstrated the complementary nature of organocatalysis and organometallic methods.
      Degree
      Doctor of Philosophy (Ph.D.)
      Department
      Chemistry
      Program
      Chemistry
      Supervisor
      Majewski, Marek
      Committee
      Sawicki, Grzegorz; Pedras, Soledade; Sanders, David A. R.; Palmer, David; Green, James R.
      Copyright Date
      June 2010
      URI
      http://hdl.handle.net/10388/etd-06302010-234123
      Subject
      proline
      aldol reactions
      Dioxanone
      carbohydrates and higher monosaccharides
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