Applications of Friedel-Crafts reactions in total synthesis of natural products

Abstract

Over the years, Friedel-Crafts (FC) reactions have been acknowledged as the most useful and powerful synthetic tools for the construction of a special kind of carbon-carbon bond involving an aromatic moiety. Its stoichiometric and, more recently, its catalytic procedures have extensively been studied. This reaction in recent years has frequently been used as a key step (steps) in the total synthesis of natural products and targeted complex bioactive molecules. In this review, we try to underscore the applications of intermolecular and intramolecular FC reactions in the total syntheses of natural products and complex molecules, exhibiting diverse biological properties.

Scheme 1. Total synthesis of africanol 1.

Scheme 2. Total synthesis of (−)-α-conidendrin 10.

Scheme 3. Total synthesis of natural products (−)-serratoline 13, (+)-aristotelone 14 and (−)-alloaristoteline 15.

Scheme 4. Total synthesis of phomazarin 20.

Scheme 5. The formation of the tricyclic product 30.

Scheme 6. Total synthesis of (−)-alliacol A 25.

Scheme 7. Total synthesis of pygmaeocin C 34.

Scheme 8. Total synthesis of tricyclic myrmicarins 43a–c.

Scheme 9. Total synthesis of salvadione 48.

Scheme 10. Total synthesis of trans-dehydrocalamenene 55.

Scheme 11. Total synthesis of erogorgiaene 58.

Scheme 12. Total synthesis of bruguierol C 62.

Scheme 13. Total synthesis of murrayazoline 67.

Scheme 14. Total synthesis of cacalol 75.

Scheme 15. Synthesis of 4a-methyltetrahydrofluorene 83 framework.

Scheme 16. Total synthesis of taiwaniaquinone H 80.

Scheme 17. Total synthesis of (−)-plicatic acid 85.

Scheme 18. Total synthesis of clavilactone D 89.

Scheme 19. Total synthesis of hainanensine 95.

Scheme 20. Total synthesis of (±)-microstegiol 99.

Scheme 21. Enantioselective total synthesis of (+)-aphanorphine 105.

Scheme 22. Total synthesis of (+)-aphanorphine 105.

Scheme 23. Total synthesis of elisapterosin B 112.

Scheme 24. Total synthesis of erogorgiaene 116.

Scheme 25. Total synthesis of hainanensine 95a and its dimethoxy analogue 95b.

Scheme 26. Total synthesis of laetevirenol A 120.

Scheme 27. Total synthesis of kealiinines A–C 126a–c.

Scheme 28. Total synthesis of diptoindonesin D 130 and pauciflorial F 131.

Scheme 29. Total synthesis of cedrelin A 138.

Scheme 30. Total synthesis of methylated paralycolin B 139.

Scheme 31. Total synthesis of (+)-9-oxoeuyopsin 146.

Scheme 32. Total synthesis of tricyclic o-hydroxy-p-quinone methide diterpenoid 149 and analogues.

Scheme 33. Total synthesis of product 155.

Scheme 34. Total synthesis of (+)-bionectins A 156 and C 157.

Scheme 35. Total synthesis of ammosamide B 161.

Scheme 36. Total synthesis of kealiiquinone A 164a and the 2-amino congener 164b.

Scheme 37. Total synthesis of ellipticines 166a and 166b.

Scheme 38. Total synthesis of gymnothelignan N 170.

Scheme 39. Total synthesis of mersicarpine 174.

Scheme 40. Total synthesis of musellarins A–C 179a–c.

Scheme 41. Total synthesis of (+)-cylindradine A 185.

Scheme 42. Total synthesis of (−)-haouamine B 191 and haouamine B pentaacetate 192.

Scheme 43. Total synthesis of gibberellins 197a or ent-kauranes 197b.

Scheme 44. Total synthesis of (−)-alstoscholarisine A 201.

Scheme 45. Total synthesis of 13-epi-mulinolic acid ethyl ester 209, 13-epi-mulinolic acid 210, mulin-11,13-dien-20-oic acid 211, 13-epi-mulinol 212, 16-hydroxymulin-11,13-dien-20-oic acid 213, mulinic acid 214 mulin-11,13-dien-20-ol 215, 20-hydroxy mulin-11,13-dienyl acetate 216 and isomulinic acid 217.

Scheme 46. Total synthesis of racemic compounds of (±)-218a, (±)-218b, (±)-218c, and (±)-218d.

Scheme 47. Total synthesis of brasiliquinone B 223.

Scheme 48. Total synthesis of methyl 3-(2,4,5-trimethoxyphenyl)propionate 228.

Scheme 49. Total synthesis of (−)-podophyllotoxin 231.

Scheme 50. Total synthesis of (+)-haplophytine 236.

Scheme 51. Total synthesis of triaryl methyl ester 250 and tetracyclic model system 257.

Scheme 52. The formation of compound 260.

Scheme 53. The formation of product 263.

Scheme 54. The formation of products 268 and 269.

Scheme 55. Total synthesis of (−)-hopeahainol A 244 and (−)-hopeanol 245.

Scheme 56. Total synthesis of dictyodendrin A 275.

Scheme 57. Total synthesis of dictyodendrin B 276.

Scheme 58. Total synthesis of (−)-ardeemin 284a, (−)-acetylardeemin 284b and (−)-formylardeemin 285.

Scheme 59. Total synthesis of (+)-gliocladin B 289 and C 290.

Scheme 60. Total synthesis of licochalcone C 295a and its regioisomer licochalcone H 295b.

Scheme 61. Total synthesis of yuehchukene 299.

Scheme 62. Total synthesis of ellipticine quinone 305.

Scheme 63. Total synthesis of (+)-hostmanin A 309, (+)-methyllinderatin 310, (+)-linderol A 312 and adunctin E 311.

Scheme 64. The formation of compounds 316 and 321.

Scheme 65. Total synthesis of catenarin 322a and erythroglaucin 322b.

Scheme 66. Total synthesis of (±)-frondosin B 326.

Scheme 67. The formation of compound 333.

Scheme 68. Total synthesis of (±)-echinofuran 330.

Scheme 69. Total synthesis of preussomerin L 336 and preussomerin K 337.

Scheme 70. Total synthesis of preussomerins L 336, K 337 and F 342.

Scheme 71. Total synthesis of 4-methoxy-1H-phenalen-1-one (4-methoxyperinaphthenone) 343.

Scheme 72. Total synthesis of sporostatin 347.

Scheme 73. Total synthesis of aaptamine 352.

Scheme 74. Total synthesis of sporostatin 347.

Scheme 75. Total synthesis of xestodecalactone C 346.

Scheme 76. Total synthesis of (11β)-11-methoxycurvularin 363.

Scheme 77. Total synthesis of diptoindonesin G 366.

Scheme 78. Total synthesis of diptoindonesin G 366.

Scheme 79. Total synthesis of prekinamycin 373.

Scheme 80. Total synthesis of FL-120B′ 378.

Scheme 81. Total synthesis of (+)-cis-trikentrin 382 and (+)-cis-trikentrin-B 383.

Scheme 82. Total synthesis of trans-dihydronarciclasine 388.

Scheme 83. Total synthesis of allocolchicinoids rac-393a and rac-393b.

Scheme 84. The formation of the simplified kibdelone tetrahydroxanthone analogue 402.

Scheme 85. Total synthesis of kibdelone A 397.

Scheme 86. Total synthesis of sandresolide B 407.

Scheme 87. Total synthesis of daphenylline 412.

Scheme 88. Total synthesis of sparstolonin B (SsnB) 416.

Scheme 89. Total synthesis of picropodophyllin 420.

Scheme 90. Total synthesis of jamaicin 424a and calopogonium isoflavone-B 424b.

Scheme 91. Total synthesis of (±)-totaryl methyl ether 428 and (+)-semperviryl methyl ether 429.

Scheme 92. Total synthesis of duocannycin A 436.

Scheme 93. Ikimine A (α-methyl-3-pyridinedodecanal-O-methyloxime) 440.

Scheme 94. Total synthesis of tolypocladin 444 and isomeric isotolypocladin 445.

Scheme 95. Total synthesis of (+)-calanolide A 449.

Scheme 96. Total synthesis of kaempferol 453.

Scheme 97. Total synthesis of phenylanthraquinones knipholone 457a, knipholone anthrone 457b, 6′-O-methylknipholone 457c and 4′-O-demethylknipholone 457d.

Scheme 98. Total synthesis of polycitone B 462 and polycitone A 463.

Scheme 99. Total synthesis of 0231B 467.

Scheme 100. Total synthesis of (±)-taiwaniaquinol B 470.

Scheme 101. Total synthesis of (±)-dichroanone 471.

Scheme 102. Total synthesis of protein tyrosine phosphatase 1B (PTP1B).

Scheme 103. Total synthesis of topopyrone A 482a, B 482b, C 482c and D 482d.

Scheme 104. Total synthesis of tylophorine 486a, deoxytylophorinine 486b, and antofine 486c.

Scheme 105. Total synthesis of lamellarin G trimethyl ether 491.

Scheme 106. Total synthesis of ialibinone A 495a and ialibinone B 495b.

Scheme 107. Total synthesis of lactonamycin 498.

Scheme 108. Total synthesis of myrtucommulone A 502.

Scheme 109. Total synthesis of 13aα-secoantofine 506 and antofine 507.

Scheme 110. Total synthesis of cytosporone B 510.

Scheme 111. Total synthesis of bruguierol A 517.

Scheme 112. Total synthesis of isomalyngamide 520 and malyngamide M 521.

Scheme 113. Total synthesis of marinopyrrole A (±)-524.

Scheme 114. Total synthesis of mono-arylated marinopyrrole 530.

Scheme 115. Total synthesis of tenuifolin 531.

Scheme 116. Total synthesis of dictyodendrins A–E.

Scheme 117. Total synthesis of (±)-heritonin 543 and (±)-heritol 544.

Scheme 118. Total synthesis of lysidicin A 550.

Scheme 119. Formation of a mixture of mono-, di- and tri-brominated products 557, 558 and 559.

Scheme 120. Total synthesis of 5-chloro-armeniaspirol 554.

Scheme 121. Synthesis of norartocarpin 567 and artocarpin 568.

Scheme 122. Total synthesis of (±)-mimosifoliol 571.

Scheme 123. Total synthesis of rhodomyrtosone B 575.

Scheme 124. Synthesis of rhodomyrtone 576.

Scheme 125. Enantioselective synthesis of (+)-conocarpan 581.

Scheme 126. Total synthesis of marmycin A 585.

Scheme 127. The formation of quaternary alcohols 586 and 587.

Scheme 128. Total synthesis of marinamide 596.

Scheme 129. Total synthesis of monosporascone 603.

Scheme 130. Total synthesis of compound 614.

Scheme 131. The formation of compound 617.

Scheme 132. Total synthesis of (−)-platensimycin 607.

Scheme 133. Total synthesis of 3-geranyl-1-(2′-methylpropanoyl)phloroglucinol 618.

Scheme 134. Total synthesis of merochlorin A 620.

Scheme 135. Total synthesis of curvulone B 624.

Scheme 136. Total synthesis of triumphalone 629 and isotriumphalone 630.

Scheme 137. Total synthesis of taccabulin E 633.

Scheme 138. Total synthesis of furan-cyclized diarylheptanoid 637.

Scheme 139. Total synthesis of furan-cyclized diarylheptanoid 638.

Scheme 140. Total synthesis of stigmatellin A 644.

Scheme 141. Total synthesis of γ-lycorane 647.

Scheme 142. Total synthesis of oxacalothrixin B 653a–f.

Scheme 143. Total synthesis of mammeasins C 656 and 657.

Scheme 144. Total synthesis of 6-tert-butyl-4′-methoxypuerarin 665a and 6-tert-butyl puerarin 665b.

Scheme 145. Total synthesis of (−)-talaumidin 670.

Scheme 146. The formation of the bicyclic compound 679.

Scheme 147. The formation of 4,5-dihydro-4′-O-methylsceletenone 680b into O-methyljoubertiamine 681.

Scheme 148. Total synthesis of (2)-talaumidin 683 and (2)-galbelgin 684.

Scheme 149. Total synthesis of (−)-cyclogalgravin 688 and (−)-8′-epi-aristoligone 689.

Scheme 150. Total synthesis of (−)-pycnanthulignene B 697 and (−)-8′-epi-aristotetralone 698.

Scheme 151. Total synthesis of santalin Y 701.

Scheme 152. Total synthesis of (+)-luteoalbusin A 704 and (+)-luteoalbusin B 705.

Scheme 153. Total synthesis of sespenine 709.

Majid M. Heravi

Vahideh Zadsirjan

Pegah Saedi

Tayebeh Momeni