Synthetic studies of complex immunostimulants from Quillaja saponaria: Synthesis of the potent clinical immunoadjuvant QS-21A(api)

• Published in: Journal of the American Chemical Society Vol. 128; no. 36; pp. 11906 - 11915
• Main Authors: Kim, Yong-Jae, Wang, Pengfei, Navarro-Villalobos, Mauricio, Rohde, Bridget D., Derryberry, JohnMark, Gin, David Y.
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 13.09.2006
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; CANCER PATIENTS; KEYHOLE LIMPET HEMOCYANIN; ACID; GLYCAL DONORS; DEHYDRATIVE GLYCOSYLATION; CONJUGATE; CATALYST; EFFICIENT; TRIS(PENTAFLUOROPHENYL)BORON; SAPONIN ADJUVANT QS-21
• ISSN: 0002-7863
• DOI: 10.1021/ja062364i

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.