Alpha-c-galactosylceramides: synthesis and immunology.
The immunostimulant activity of alpha-galactosylceramides provided the impetus for the research described here. The activity was first discovered via screening of extracts of a marine sponge. The active materials purified from the extracts were alpha-O-galactosylceramides. The work described herein focuses on syntheses of alpha-C-galactosylceramides. Crucial methodologies for the syntheses were (i) Ramberg-Bäcklund reaction, (ii) modified Julia olefination, (iii) olefin cross-metathesis, and (iv) Sharpless asymmetric epoxidation in four independent routes. The immunostimulant activity of the synthetic alpha-C-galactosylceramide far surpasses that of the O-galactosyl material. A discussion of the reasons for the difference in activity is presented.
Franck
Richard W
RW
Department of Chemistry and Biochemistry, Hunter College of The City University of New York, 695 Park Avenue, New York, NY 10021, USA.
Tsuji
Moriya
M
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D018360:Crystallography, X-Ray; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000276:immunology* / Q000494:pharmacology; D007109:Immunity / Q000187:drug effects*; D051379:Mice; D008958:Models, Molecular; D011161:Porifera / Q000737:chemistry
D000276:Adjuvants, Immunologic; D016207:Cytokines; D005699:Galactosylceramides; C103873:KRN 7000