New synthesis of glycolipid immunostimulants RC-529 and CRX-524

Hélène G. Bazin; Laura S. Bess; Mark T. Livesay; Kendal T. Ryter; Craig L. Johnson; Jeffrey S. Arnold; David A. Johnson

doi:10.1016/j.tetlet.2006.01.137

New synthesis of glycolipid immunostimulants RC-529 and CRX-524

Hélène G. Bazin
, Laura S. Bess
, Mark T. Livesay
, Kendal T. Ryter
, Craig L. Johnson
, Jeffrey S. Arnold
, David A. Johnson

Center for Translational Medicine

GlaxoSmithKline

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

An efficient and scalable synthesis of the potent vaccine adjuvant RC-529 (3) and TLR4 agonist CRX-524 (4) is described in eight steps from 1,3,4,6-tetra-O-acetyl-2-amino-2-benzyloxycarbonyl-2-deoxy-β-d- glucopyranose (10c) in ca. 25% overall yield. The synthesis features the strategic use of the N-Cbz group for β-glycosylation and the selective N,N,O-triacylation of common advanced intermediate 15 with (R)-3- tetradecanoyloxy or decanoyloxytetradecanoic acid (8, 9) late in the synthesis. A new method for preparing and enhancing the enantiopurity of (R)-3-hydroxytetradecanoic acid (6), a key component of 3 and 4 as well as bacterial lipid A, is also described.

Original language	English
Pages (from-to)	2087-2092
Number of pages	6
Journal	Tetrahedron Letters
Volume	47
Issue number	13
DOIs	https://doi.org/10.1016/j.tetlet.2006.01.137
State	Published - Mar 27 2006

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

AGP
Glycolipids
Immunostimulants
Lipid A mimetics
TLR4 agonist
Vaccine adjuvant

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10.1016/j.tetlet.2006.01.137

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title = "New synthesis of glycolipid immunostimulants RC-529 and CRX-524",

abstract = "An efficient and scalable synthesis of the potent vaccine adjuvant RC-529 (3) and TLR4 agonist CRX-524 (4) is described in eight steps from 1,3,4,6-tetra-O-acetyl-2-amino-2-benzyloxycarbonyl-2-deoxy-β-d- glucopyranose (10c) in ca. 25\% overall yield. The synthesis features the strategic use of the N-Cbz group for β-glycosylation and the selective N,N,O-triacylation of common advanced intermediate 15 with (R)-3- tetradecanoyloxy or decanoyloxytetradecanoic acid (8, 9) late in the synthesis. A new method for preparing and enhancing the enantiopurity of (R)-3-hydroxytetradecanoic acid (6), a key component of 3 and 4 as well as bacterial lipid A, is also described.",

keywords = "AGP, Glycolipids, Immunostimulants, Lipid A mimetics, TLR4 agonist, Vaccine adjuvant",

author = "Bazin, \{H{\'e}l{\`e}ne G.\} and Bess, \{Laura S.\} and Livesay, \{Mark T.\} and Ryter, \{Kendal T.\} and Johnson, \{Craig L.\} and Arnold, \{Jeffrey S.\} and Johnson, \{David A.\}",

year = "2006",

month = mar,

day = "27",

doi = "10.1016/j.tetlet.2006.01.137",

language = "English",

volume = "47",

pages = "2087--2092",

journal = "Tetrahedron Letters",

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T1 - New synthesis of glycolipid immunostimulants RC-529 and CRX-524

AU - Bazin, Hélène G.

AU - Bess, Laura S.

AU - Livesay, Mark T.

AU - Ryter, Kendal T.

AU - Johnson, Craig L.

AU - Arnold, Jeffrey S.

AU - Johnson, David A.

PY - 2006/3/27

Y1 - 2006/3/27

N2 - An efficient and scalable synthesis of the potent vaccine adjuvant RC-529 (3) and TLR4 agonist CRX-524 (4) is described in eight steps from 1,3,4,6-tetra-O-acetyl-2-amino-2-benzyloxycarbonyl-2-deoxy-β-d- glucopyranose (10c) in ca. 25% overall yield. The synthesis features the strategic use of the N-Cbz group for β-glycosylation and the selective N,N,O-triacylation of common advanced intermediate 15 with (R)-3- tetradecanoyloxy or decanoyloxytetradecanoic acid (8, 9) late in the synthesis. A new method for preparing and enhancing the enantiopurity of (R)-3-hydroxytetradecanoic acid (6), a key component of 3 and 4 as well as bacterial lipid A, is also described.

AB - An efficient and scalable synthesis of the potent vaccine adjuvant RC-529 (3) and TLR4 agonist CRX-524 (4) is described in eight steps from 1,3,4,6-tetra-O-acetyl-2-amino-2-benzyloxycarbonyl-2-deoxy-β-d- glucopyranose (10c) in ca. 25% overall yield. The synthesis features the strategic use of the N-Cbz group for β-glycosylation and the selective N,N,O-triacylation of common advanced intermediate 15 with (R)-3- tetradecanoyloxy or decanoyloxytetradecanoic acid (8, 9) late in the synthesis. A new method for preparing and enhancing the enantiopurity of (R)-3-hydroxytetradecanoic acid (6), a key component of 3 and 4 as well as bacterial lipid A, is also described.

KW - AGP

KW - Glycolipids

KW - Immunostimulants

KW - Lipid A mimetics

KW - TLR4 agonist

KW - Vaccine adjuvant

UR - https://www.scopus.com/pages/publications/33344457008

U2 - 10.1016/j.tetlet.2006.01.137

DO - 10.1016/j.tetlet.2006.01.137

M3 - Article

AN - SCOPUS:33344457008

SN - 0040-4039

VL - 47

SP - 2087

EP - 2092

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 13

ER -

New synthesis of glycolipid immunostimulants RC-529 and CRX-524

Abstract

UN SDGs

Keywords

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