Pathogen-Associated Molecular Patterns: The Synthesis of Heptose Phosphates and Derivatives

Abstract

Lipopolysaccharide biosynthesis metabolites, such as d-glycero-β-d-manno-heptopyranosyl 1,7-diphosphate, d-glycero-β-d-manno-heptopyranosyl phosphate, and adenosine 5′-(l-glycero-β-d-manno-heptopyranosyl)diphosphate, have been found to activate NF-κB via alpha-kinase 1 and TRAF-interacting protein with forkhead associated domain. This axis has been determined as a novel pathway of innate immunity yet to be targeted for immunomodulatory treatment approaches. Key in understanding this new axis has been the ability to synthesize these metabolites. The design of synthetic analogues and probes have also been published not only to design new drugs, but also to gain insight into the mechanism of action for these compounds. The focus of the present review is the synthesis of heptose phosphate metabolites­ as well as synthetic analogues and probes.

1 Introduction

2 Synthesis of d-glycero-d-manno-Heptose

2.1 Using d-Mannose as Starting Material

2.2 Using d-Ribose as Starting Material

2.3 Using 2,2-Dimethyl-1,3-dioxan-5-one as Starting Material

3 Synthesis of l-glycero-d-manno-Heptose

3.1 Using d-Mannose as Starting Material

3.2 Using 2,2-Dimethyl-1,3-dioxan-5-one as Starting Material

3.3 Using l-Lyxose as Starting Material

4 Synthesis of Heptose Phosphates

4.1 Synthesis of d-glycero-β-d-manno-Heptose 1,7-Diphosphate

4.2 Synthesis of Heptose Phosphate Derivatives

4.2.1 Development of Scaffolds for Conjugation

4.2.2 Development of Heptose Phosphates Derivatives for Cell Intake and Metabolic Stability

5 Conclusion and Outlook

Key words

heptose diphosphate - heptose monophosphate - ADP-heptose - metabolites - pathogen associated molecular patterns

Publication History

Received: 28 May 2021

Accepted after revision: 26 July 2021

Article published online:
06 September 2021

• References

• 1a Medzhitov R, Janeway CA. Jr. Science 2002; 296: 298
• 1b Amarantes-Medes GP, Adjemian S, Migliari Branco L, Zanetti LC, Weinlich R, Bortuluci KR. Front. Immunol. 2018; 9: 2379
• 1c Newton K, Dixit VM. Cold Spring Harbor Perspect. Biol. 2012; 4: a006049 ; DOI: DOI: 10.1101/cshperspect.a006049.
• 2 Zhu G, Xu Y, Cen X, Nandakumar KS, Liu S, Cheng K. Eur. J. Med. Chem. 2018; 144: 82
• 3 Kiessling LL, Splain RA. Annu. Rev. Biochem. 2010; 79: 619
• 4 Dey B, Dey RJ, Cheung LS, Pokkali S, Guo H, Lee J.-H, Bishai WR. Nat. Med. 2015; 21: 401
• 5a Gaudet RG, Sintsova A, Buckwalter CM, Leung N, Cochrane A, Li J, Cox AD, Moffat J, Gray-Owen SD. Science 2015; 348: 1251
• 5b Adekoya IA, Guo CX, Gray-Owen SD, Cox AD, Sauvageau J. J. Immunol. 2018; 201: 2385
• 5c Zhou P, She Y, Dong N, Li P, He H, Borio A, Wu Q, Lu S, Ding X, Cao Y, Xu Y, Gao W, Dong M, Ding J, Wang D.-C, Zamyatina A, Shao F. Nature 2018; 561: 122
• 5d Pfannkuch L, Hurwitz R, Traulsen J, Sigulla J, Poeschke M, Matzner L, Kosma P, Schmidt M, Meyer TF. FASEB J. 2019; 33: 9087
• 5e García-Weber D, Dangeard A.-S, Comil J, Thai L, Rytter H, Zamyatina A, Mulard LA, Arrieumerlou C. EMBO Rep. 2018; 19: e46943
• 6 García-Weber D, Arrieumerlou C. Cell. Mol. Life Sci. 2021; 78: 17
• 7a Gray-Owen S, Gaudet R, Malott R. WO 2016054745, 2016
• 7b Cox A, Sauvageau J, Oscarson S, Guazzelli L. WO 2018205009, 2018
• 7c Gray-Owen S, Guo X, Cox A, Sauvageau J. WO 2018205010, 2018
• 7d Sauvageau J, Cox A, Guo X, Gray-Owen S. WO 2019126873, 2019
• 7e Xu T, Xu C, Liu D, Fan J, Pan Y, Chen X, Li TR. WO 2019080898, 2019
• 7f Xu T, Xu C, Liu D, Fan J, Pan Y. WO 2020216327, 2020
• 7g Shao F, Zhou P, She Y, He H, Li P, Ding J, Gao W. WO 2019238024, 2019
• 8 Awate S, Bakiuk LA, Mutwiri G. Front. Immunol. 2013; 4: 114
• 9 Gaudet RG, Gray-Owen SD. PLOS Pathog. 2016; 12: e1005807
• 10a Oscarson S. Carbohydr. Chem. 2012; 38: 40
• 10b Tikad A, Vincent SP. In Modern Synthetic Methods in Carbohydrate Chemistry: From Monosaccharides to Complex Glycoconjugates. Werz D, Vidal SB. Wiley-VCH; Weinheim: 2014: 29-63
• 10c Kosma P. Curr. Org. Chem. 2008; 12: 1021
• 11 Kneidinger B, Marolda C, Graninger M, Zamyatina A, McArthur F, Kosma P, Valvano MA, Messner P. J. Bacteriol. Res. 2002; 184: 363
• 12a Brimacombe JS, Kabir AK. M. S. Carbohydr. Res. 1986; 150: 35
• 12b Brimacombe JS, Kabir AK. M. S. Carbohydr. Res. 1986; 152: 329
• 12c van Straten NC. R, Kriek NM. A. J, Timmers CM, Wigchert SC. M, van der Marel GA, van Boom JH. J. Carbohydr. Chem. 1997; 16: 947
• 12d Mulani SK, Chen K.-C, Mong K.-KT. Org. Lett. 2015; 17: 5536
• 13a Palmelund A, Madsen R. J. Org. Chem. 2005; 70: 8248
• 13b Wang J, Rong J, Lou Q, Zhu Y, Yang Y. Org. Lett. 2020; 22: 8018
• 14 Wang J, Zhang Y, Zhu Y, Liu J, Chen Y, Cao X, Yang Y. Org. Lett. 2020; 22: 8780
• 15a Sauvageau J, Bhasin M, Guo CX, Adekoya IA, Gray-Owen SD, Oscarson S, Guazzelli L, Cox A. Carbohydr. Res. 2017; 450: 38
• 15b Hu L, Zhao C, Ma J, Jing Y, Du Y. Bioorg. Med. Chem. Lett. 2019; 29: 1357
• 15c Chen FE, Zhao J.-F, Xiong F.-J, Xie B, Zhang P. Carbohydr. Res. 2007; 342: 2461
• 16a Mandal SS, Ganesh NV, Sadowska JM, Bundle DR. Org. Biomol. Chem. 2017; 15: 3874
• 16b Davis B, Brandstetter TW, Smith C, Hackett L, Winchester BG, Fleet GW. J. Tetrahedron Lett. 1995; 36: 7507
• 16c Khan SH, Matta KL. Carbohydr. Res. 1993; 243: 29
• 17 Li T, Wen L, Williams A, Wu B, Li L, Qu J, Meisner J, Xiao Z, Fang J, Wang PG. Bioorg. Med. Chem. 2014; 22: 1139
• 18 Ohara T, Adibekian A, Esposito D, Stallforth P, Seeberger PH. Chem. Commun. 2010; 46: 4106
• 19a Grzeszczyk B, Zamojski A. Carbohydr. Res. 1994; 262: 49
• 19b Boons GJ. P. H, Overhand SM, van der Marel GA, van Boom JH. J. Carbohydr. Chem. 1991; 10: 995
• 19c Berlind C, Oscarson S. J. Org. Chem. 1998; 63: 7780
• 20 Stanetty C, Baxendale IR. Eur. J. Org. Chem. 2015; 2718
• 21 Dziewiszek K, Zamojski A. Carbohydr. Res. 1986; 150: 163
• 22 Li T, Tikad A, Durka M, Pan W, Vincent SP. Carbohydr. Res. 2016; 432: 71
• 23 Suster C, Baxendale IR, Mihovilovic MD, Stanetty C. Front. Chem. 2020; 8: 625
• 24 Zamyatina A, Gronow S, Clemens O, Puchberger M, Brade H, Kosma P. Angew. Chem. Int. Ed. 2000; 39: 4150
• 25 Zamyatina A, Gronow S, Puchberger M, Graziani A, Hofinger A, Kosma P. Carbohydr. Res. 2003; 338: 2571
• 26 Nguyen H, Wang L, Huang H, Peisach E, Dunaway-Mariano D, Allen KN. Biochemistry 2010; 49: 1082
• 27a Inuki S, Aiba T, Kawakami S, Akiyama T, Inoue J.-I, Fujimoto Y. Org. Lett. 2017; 19: 3079
• 27b Borio A, Hofinger A, Kosma P, Zamyatina A. Tetrahedron Lett. 2017; 58: 2826
• 27c Liang L, Vincent SP. Tetrahedron Lett. 2017; 58: 3631
• 28a Zou X.-P, Qin C.-J, Hu J, Fu J.-J, Tian G.-Z, Moscovitz O, Seeberger PH, Yin J. Chin. J. Nat. Med. 2020; 18: 628
• 28b Williams D, Jamshidi MP, St Michael F, Chisholm K, Cox A, Sauvageau J. J. Org. Chem. 2021; 86: 2184
• 29a Szabó P. J. Chem. Soc., Perkin Trans. 1 1974; 920
• 29b Ekelöf K, Oscarson S. Carbohydr. Chem. 1995; 14: 299
• 29c Grzeszczyk B, Holst O, Zamojski A. Carbohydr. Res. 1996; 290: 1
• 29d Grzeszczyk B, Holst O, Müller-Loennies S, Zamojski A. Carbohydr. Res. 1998; 307: 55
• 29e Stewart A, Bernlind C, Martin A, Oscarson S, Richards JC, Schweda EK. H. Carbohydr. Res. 1998; 313: 193
• 29f Güzlek H, Graziani A, Kosma P. Carbohydr. Res. 2005; 340: 2808
• 29g Read JA, Ahmed RA, Tanner ME. Org. Lett. 2005; 7: 2457
• 29h Durka M, Tikad A, Périon R, Bosco M, Andaloussi M, Floquet S, Malacain E, Moreau F, Oxoby M, Gerusz V, Vincent SP. Chem. Eur. J. 2011; 17: 11305
• 30a MacDonald DL. J. Org. Chem. 1962; 27: 1107
• 30b Prihar HS, Behrman EJ. Carbohydr. Res. 1972; 23: 456
• 30c Schmidt RR, Stumpp M, Michel J. Tetrahedron Lett. 1982; 23: 405
• 30d Inage M, Chaki H, Kusumoto S, Shiba T. Chem. Lett. 1982; 11: 1281
• 30e Gokhale UB, Hindsgaul O, Palcic MM. Can. J. Chem. 1990; 68: 1063
• 30f Veeneman GH, Broxterman HJ. G, van der Marel GA, van Boom JH. Tetrahedron Lett. 1991; 32: 6175
• 30g Sabesan S, Neira S. Carbohydr. Res. 1992; 223: 169
• 30h Hanessian S, Lu P.-P, Ishida H. J. Am. Chem. Soc. 1998; 120: 13296
• 30i Plante OJ, Andrade RB, Seeberger PH. Org. Lett. 1999; 1: 211
• 30j Garcia BA, Gin DY. Org. Lett. 2000; 2: 2135
• 31a Crich D, Dudkin V. Org. Lett. 2000; 2: 3941
• 31b van Summeren RP, Moody DB, Feringa BL, Minnaard AJ. J. Am. Chem. Soc. 2006; 128: 4546
• 31c Li T, Tikad A, Pan W, Vincent SP. Org. Lett. 2014; 16: 5628
• 32a Wiemer AJ. ACS Pharmacol. Transl. Sci. 2020; 3: 613
• 32b Wiemer AJ, Wiemer DF. Top. Curr. Chem. 2020; 360: 115
• 33a Liang L, Wei T.-YW, Wu P.-Y, Herrebout W, Tsai W.-D, Vincent SP. ChemBioChem 2020; 20: 2982
• 33b Li T, Tikad A, Fu H, Milicaj J, Castro CD, Lacritick M, Pan W, Taylor EA, Vincent SP. Org. Lett. 2021; 23: 1638
• 33c Liang L, Cao J, Wade Wei T.-Y, Tsai M.-D, Vincent SP. Org. Biomol. Chem. 2021; 19: 4943
• 34 Rautio J, Meanwell NA, Di L, Hageman MJ. Nat. Rev. 2018; 17: 559