C-Glycopyranosyl aldehydes: emerging chiral synthons in organic synthesis

Abstract

Herein, we have summarized the vast array of synthetic processes that have been developed for the synthesis of C-glycopyranosyl aldehydes and diverse C-glycoconjugates derived from them by covering the literature reported from 1979 to 2023. Notwithstanding its challenging chemistry, C-glycosides are considered stable pharmacophores and are used as important bioactive molecules. The discussed synthetic methodologies to access C-glycopyranosyl aldehydes take advantage of seven key intermediates, viz. allene, thiazole, dithiane, cyanide, alkene, and nitromethane. Furthermore, the integration of complex C-glycoconjugates derived from varied C-glycopyranosyl aldehydes involves nucleophilic addition/substitution, reduction, condensation, oxidation, cyclo condensation, coupling, and Wittig reactions. In this review, we have categorized the synthesis of C-glycopyranosyl aldehydes and C-glycoconjugates on the basis of the methodology used for their synthesis and on types of C-glycoconjugates, respectively.

Fig. 1. Structures of some selected naturally occurring bioactive C-glycosides.

Fig. 2. Structures of some bioactive synthetic C-glycosides.

Fig. 3. Key intermediates for the synthesis of C-glycopyranosyl aldehydes.

Scheme 1. Synthesis of β-C-glycopyranosyl aldehydes 4a–c.

Scheme 2. Synthesis of α-C-galactopyranosyl aldehyde 7.

Scheme 3. Synthesis of β-C-galactopyranosyl aldehyde 4c.

Scheme 4. Synthesis of α-C-galactopyranosyl aldehyde 11.

Scheme 5. Synthesis of β-C-glucopyranosyl aldehyde 4a.

Scheme 6. Synthesis of C-glycopyranosyl aldehydes 4a–d.

Scheme 7. The conversion process of 17a–d into 19a–dvia two pathways, A and B.

Scheme 8. Synthesis of C-glucopyranosyl aldehyde 4a.

Scheme 9. Synthesis of β-C-glucopyranosyl aldehyde 4a.

Scheme 10. Synthesis of β-C-glucopyranosyl aldehyde 4a.

Scheme 11. Synthesis of β-C-glycopyranosyl aldehyde 37.

Scheme 12. Synthesis of C-glycopyranosyl aldehydes 39a–f, 40a–c, 43a–b.

Scheme 13. Synthesis of α-C-glucopyranosyl aldehyde 3a.

Scheme 14. Synthesis of β-C-galactopyranosyl aldehyde 50.

Scheme 15. Synthesis of α-C-glycopyranosyl aldehyde 56.

Scheme 16. Synthesis of C-glycopyranosyl aldehydes 59a–f.

Scheme 17. Synthesis of β-C-glucopyranosyl aldehydes 65a and 4a.

Scheme 18. Synthesis of β-C-glycopyranosyl aldehydes 73a–g.

Scheme 19. Synthesis of C-glycopyranosyl aldehydes 78a–b.

Scheme 20. Synthesis of α-C-glycopyranosyl aldehyde 3a.

Scheme 21. Synthesis of α-C-glycopyranosyl aldehyde 4a.

Scheme 22. Synthesis of α-C-glycopyranosyl aldehyde 90.

Scheme 23. Synthesis of α-C-galactopyranosyl aldehyde 3c.

Scheme 24. Synthesis of α-C-galactopyranosyl aldehyde 96.

Scheme 25. Synthesis of α-C-glucopyranosyl aldehyde 102.

Scheme 26. Synthesis of C-glycopyranosyl aldehydes 108a–b.

Scheme 27. Synthesis of β-C-glycopyranosyl aldehydes 4a–c.

Scheme 28. Synthesis of β-C-glucopyranosyl aldehyde 65a.

Scheme 29. Synthesis of C-glycopyranosyl aldehyde 122.

Scheme 30. Synthesis of β-C-glycopyranosyl aldehydes 2a–d.

Fig. 4. Structures of various biologically important C-glycoconjugates derived from C-glycopyranosyl aldehyde.

Scheme 31. Synthesis of galactosphingo lipid 130.

Scheme 32. (a) Synthesis of α-GalCer analogues 149 and 151. (b) Synthesis of α-GalCer analogues 153 and 156.

Scheme 33. Synthesis of α-C-galactosylceramides 129a–c.

Scheme 34. Synthesis of β-d-galactosyl ceramide methylene isostere 171 and 172.

Scheme 35. Synthesis of disaccharide 180.

Scheme 36. Synthesis of C-linked disaccharides 187, 192, 193, and 200.

Scheme 37. (a) Synthesis of disaccharides 132a–b. (b) Synthesis of β-d-galactopyranosyl-d-galactal 132c.

Scheme 38. (a) Synthesis of β-C-galactopyranosyl disaccharide 220. (b) Synthesis of β-C-glycopyranosyl disaccharide 225.

Scheme 39. (a) Synthesis of antigen 131a. (b) Synthesis of antigen 131b.

Scheme 40. Synthesis of C-linked disaccharide 253a–c.

Scheme 41. Synthesis of β-d-C-manno-pyranoside 258.

Scheme 42. Synthesis of β-(1→4)-C-disaccharides 264 and 265.

Scheme 43. Synthesis of C-disaccharide 273a–b.

Scheme 44. Synthesis of (1→6)-C-disaccharides 277 and 280.

Scheme 45. (a) Synthesis of oligosaccharide 290. (b) Synthesis of oligosaccharide 300.

Scheme 46. Synthesis of 2-amino-2-C-d-glycosyl-acetonitriles 301a–b, 302a–b, 303.

Scheme 47. Synthesis of C-glycopyranosyl propargylic alcohol 307.

Scheme 48. Synthesis of C-glycopyranosyl β-amino acids 311, 313, 315, 320.

Scheme 49. Synthesis of C-glycosyl amino acids 325a–c.

Scheme 50. Synthesis of C-glycosyl amino acids 133a–b.

Scheme 51. (a) Synthesis of δ-substituted pyranoid sugar amino acid 333. (b) Synthesis of l,l-dipeptides isosters 340a–d.

Scheme 52. Synthesis of C-galactopyranosyl-β-lactams 342a–g, α-amino ester 346, C-galactosyl isoserine methyl ester 348.

Scheme 53. Synthesis of β-d-galactopyranosyl-l-serine 353.

Scheme 54. Synthesis of C-glucopyranosyl-α-amino acid 355.

Scheme 55. Synthesis of C-glycosyl norstatines (α-hydroxy-β-amino acids) 365e–h.

Scheme 56. Synthesis of depsipeptides 369a–t and 370a.

Scheme 57. Synthesis of benzylated cyclic tetramer 381.

Scheme 58. Synthesis of 2,6-anhydro heptitol 383a–c and sugar-amino acid hybrid macrocycles 386–388.

Scheme 59. Synthesis of C-AFGP analogue 125.

Scheme 60. Synthesis of compounds 398, 401, and 402.

Scheme 61. Synthesis of C-mannosides analogues 128a–b and 406.

Scheme 62. Synthesis of benzyl-α-C-glucosides and anilinomethyl-α-C-glucosides 412a–d.

Scheme 63. Synthesis of C-(α-d-glucopyranosyl)-phenyldiazomethanes 426a–d.

Scheme 64. Synthesis of β-C-glycosides 430–433.

Scheme 65. Synthesis of C-β-d-glucosides 126a–p and 127a–d.

Scheme 66. Synthesis of C-glycosides 440 and 441.

Scheme 67. Synthesis of various sugar-based dihydropyrimidinones.

Scheme 68. Synthesis of 3-glycosylated isocoumarins 453, 458, and 462.

Scheme 69. Synthesis of C-aryl glucoside 467–469.

Scheme 70. Synthesis of glycopyranosyl pyridine and pyrazole derivatives 479 and 480.

Scheme 71. Synthesis of C-glycosylated dihydropyridine 482b–c.

Scheme 72. Synthesis of homonucleosides 485a–d and 488a–c.

Scheme 73. Synthesis of glycosyl nitrile oxide 490a and glycosyl nitrones 492a–d.

Scheme 74. Synthesis of 2-β-d-glucopyranosyl pyridines 502a–f.

Scheme 75. Synthesis of C-glucosides of 1-azaindolizines 505a–n and 506.

Scheme 76. (a) Synthesis of tetra-O-benzylated cyclopropane 512. (b) Synthesis of the western part of Ambruticin 519.

Scheme 77. Synthesis of sugar-based building blocks for the Ugi reaction, i.e. acid 520, amine 522, and isocyanide 523.

Scheme 78. Synthesis of [60]fulleropyrrolidine glycoconjugates 527a–b and 528b.

Scheme 79. Synthesis of C-glucopyranosyl vinyl iodide 529.

Scheme 80. Synthesis of organometallic C-glycosides 531.

Scheme 81. Synthesis of l-sugar derivatives 536a–b.

Scheme 82. Synthesis of 2-(β-d-glycopyranosyl)nitroethenes and -nitroethanes 539a–d & 541a–d.

Scheme 83. Synthesis of 1,6-anhydro-2,3-dideoxy-3(S)-d-glycero-L-gluco-(3-²H)nonopyranose 550 and 551.

Scheme 84. Synthesis of gluco- and manno-heptitol-PEG copolymers 552 and 553.

Scheme 85. Synthesis of (2R,3S,4R)-chromanes 558a–i.

Sandeep Kumar

Vinod Khatri

Priyanka Mangla

Rajni Johar Chhatwal

Virinder S. Parmar

Ashok K. Prasad