Douglas P Izmirian

Publications (2)8.9 Total impact

• Article: Synthesis and evaluation of sphinganine analogues of KRN7000 and OCH.

  Rachel M Ndonye, Douglas P Izmirian, Matthew F Dunn, Karl O A Yu, Steven A Porcelli, Archana Khurana, Mitchell Kronenberg, Stewart K Richardson, Amy R Howell
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  ABSTRACT: [structures: see text] The phytosphingosine-containing alpha-galactosylceramides (alpha-GalCers), KRN7000 and OCH, have been shown to activate NKT cells via interaction with CD1d, a member of the CD1 family of antigen presenting proteins. Evidence from KRN7000 stimulation of NKT cells suggests that alpha-GalCers may have applications in the treatment or prevention of a range of viral, bacterial, and autoimmune conditions. Moreover, OCH, a truncated analogue of KRN7000, appears to induce a T(H)2 bias, which could have implications for the treatment of autoimmune and inflammatory conditions. We have prepared the direct sphinganine-containing analogues of KRN7000 and OCH, 1 and 2, and found them to be comparable in activity to the parent compounds in inducing the release of IL-2, IL-4, and IFNgamma. In addition, compound 2 leads to a cytokine bias similar to that seen with OCH. This is significant because sphinganines are more easily accessed than phytosphingosines, which should facilitate SAR studies.
  The Journal of Organic Chemistry 01/2006; 70(25):10260-70. · 4.45 Impact Factor
• Article: Straightforward synthesis of sphinganines via a serine-derived Weinreb amide.

  Regina C So, Rachel Ndonye, Douglas P Izmirian, Stewart K Richardson, Robyn L Guerrera, Amy R Howell
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  ABSTRACT: Sphinganines can be synthesized in just three steps from easily prepared serine-derived Weinreb amide 4. Pre-deprotonation of the acidic (N-H and O-H) protons of 4 allows for its efficient conversion to amino ketones 5. Such ketones can be selectively reduced to either erythro- or threo-sphinganines. Partially protected sphinganines 11 are also readily accessible in five steps from 4. Thus, Weinreb amide 4 represents one of the most versatile templates described to date for sphinganine synthesis.
  The Journal of Organic Chemistry 05/2004; 69(9):3233-5. · 4.45 Impact Factor