Synthetic studies of complex immunostimulants from Quillaja saponaria: synthesis of the potent clinical immunoadjuvant QS-21Aapi.
QS-21 is one of the most promising new adjuvants for immune response potentiation and dose-sparing in vaccine therapy given its exceedingly high level of potency and its favorable toxicity profile. Melanoma, breast cancer, small cell lung cancer, prostate cancer, HIV-1, and malaria are among the numerous maladies targeted in more than 80 recent and ongoing vaccine therapy clinical trials involving QS-21 as a critical adjuvant component for immune response augmentation. QS-21 is a natural product immunostimulatory adjuvant, eliciting both T-cell- and antibody-mediated immune responses with microgram doses. Herein is reported the synthesis of QS-21A(api) in a highly modular strategy, applying novel glycosylation methodologies to a convergent construction of the potent saponin immunostimulant. The chemical synthesis of QS-21 offers unique opportunities to probe its mode of biological action through the preparation of otherwise unattainable nonnatural saponin analogues.
Kim
Yong-Jae
YJ
Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA.
Wang
Pengfei
P
Navarro-Villalobos
Mauricio
M
Rohde
Bridget D
BD
Derryberry
JohnMark
J
Gin
David Y
DY
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry; D002240:Carbohydrate Sequence; D008969:Molecular Sequence Data; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D031990:Quillaja / Q000737:chemistry* / Q000276:immunology; D012502:Sapogenins / Q000737:chemistry; D012503:Saponins / Q000138:chemical synthesis* / Q000737:chemistry; D014312:Trisaccharides / Q000138:chemical synthesis / Q000737:chemistry
D000276:Adjuvants, Immunologic; D012502:Sapogenins; D012503:Saponins; D014312:Trisaccharides; C078785:saponin QA-21V1; C005564:quillaic acid; D009828:Oleanolic Acid