Total Synthesis Highlights

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developed (J. Am. Chem. Soc. 2010, 132, 371.) a practical synthetic route to 3 based on the convergent coupling of 1 and 2. The preparation of 1 was based on the intramolecular [4+2] cyclization of the furan 9, prepared by Friedel-Crafts acylation of furan (4) with maleic anhydride (5). The absolute configuration of the secondary alcohol was set by Noyori reduction, using sodium formate as the hydride source. The cyclization of 9 to 10 proceeded with high diastereocontrol, presumably by way of a chelated transition state. As expected, cyclization of the silyl ether of 9 delivered the complementary diastereomer. As the cyclization of 9 was readily reversible, it was taken quickly to the bromide 11. Oxidative cleavage of the diol followed by selective reduction and protection then completed the synthesis of 1. The preparation of 2 began with the commercial bromo acid 12. The enantiomerically-enriched epoxide 13 was constructed in the usual way, by homologation of the aldehyde to the allylic alcohol followed by Sharpless epoxidation. On exposure to the Yamamoto catalyst, 13 smoothly rearranged to the aldehyde 14. Condensation of 14 with 15 then gave 16, with only minimal erosion of enantiomeric excess over the two steps. Unfortunately, 16 was the incorrect diastereomer, so it had to be inverted. With the aldehyde 17 in hand, conversion to the dichloride followed by functional group interchange completed the construction of 2.
Carbonylative coupling of 1 and 2 led to the enone 18. The photochemical Nazarov cyclization of 18 proceeded with the expected high diastereocontrol, to give, after epimerization, the desired trans-anti-trans product. Deprotection then completed the synthesis of (-)-Nakiterpiosin (3). It is noteworthy that the full A-ring functionality of 3 was compatible with the conditions of the photochemical cyclization. The work of Chen toward the total synthesis of (-)-nakiterpoisin (3) led to a correction of the relative configurations both of the dichloromethyl substituent and of the secondary bromide. The availability of 3 by total synthesis is particularly exciting, because it has been shown to interfere with the Hedgehog signaling pathway. There is the potential, based on this activity, that derivatives of 3 may prove useful as adjuncts in cancer chemotherapy. D. F. Taber, Org. Chem. Highlights 2010, December 6. URL: http://www.organic-chemistry.org/Highlights/2010/06December.shtm 5. The Shair Synthesis of Cephalostatin 1 The cephalostatins and ritterazines, represented by Cephalostatin 1 (3), have the remarkable property of inducing apoptosis in apoptosis-resistant malignant cell lines. The total synthesis (J. Am. Chem. Soc. 2010, 132, 275. DOI: 10.1021/ja906996c) of 3 by Matthew D. Shair of Harvard University required the practical preparation of the complex hexacyclic ketones 1 and 2. The preparation of 1 started with irradiation of commercial hecogenin acetate 4 to give the known aldehyde 5. Reaction of 5 with N-phenyltriazolenedione (6) led to the ketal 7. Oxidative cleavage generated an aldehyde, that on reduction and allylation was converted to 8. Acid-mediated cyclization led to 9.
Page 1 and 2: 近年来完成的天然产
Page 3 and 4: The starting point for the synthesi
Page 5: The side chain nitrile was prepared
Page 9 and 10: 6. The Overman Synthesis of Briarel
Page 11 and 12: There were two remaining problems i
Page 13 and 14: The iodide 19 was enantiomerically
Page 15 and 16: To complete the synthesis of 3, it
Page 17 and 18: The assembly of 2 began with the li
Page 19 and 20: The synthesis of the aromatic porti
Page 21 and 22: Pseudolaric Acid B (3) would be der
Page 23 and 24: Reduction of the ketone then set th
Page 25 and 26: The absolute configuration of 1 was
Page 27 and 28: The keto phosphonate 16 for the las
Page 29 and 30: Nakamura reagent delivered the ally
Page 31 and 32: 21. The Overman Syntheses of Nankak
Page 33 and 34: The benzyloxy aldehyde 1 was prepar
Page 35 and 36: Debenzylation of 11 followed by ace
Page 37 and 38: The Hoveyda Synthesis of (-)-Clavir
Page 39 and 40: eduction of 8 delivered the primary
Page 41 and 42: The seemingly simple task of conver
Page 43 and 44: fermentation of halogenated aromati
Page 45 and 46: The octaene 1 was assembled from fo
Page 47 and 48: The starting point for the preparat
Page 49 and 50: Several aspects of this synthesis a
Page 51 and 52: To achieve the syn relative (and ab
Page 53 and 54: The diol 6 is C 2 -symmetrical, but
Page 55 and 56: The last challenge was the establis
Page 57 and 58:
(+)-Discodermolide (3), a potent an
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Evans auxiliary-controlled homologa
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39. The Clark Synthesis of Vigulari
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The preparation of 1 began with the
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The preparation of 2 began with Cu-
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With 3 in hand, what remained was a
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44. The Padwa Synthesis of Asphidop
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The aldehyde 1 was in fact not isol
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47. The Nicolaou Synthesis of Plate
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The enantiomercially-pure cyclopent
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Although the tandem ring closing me
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procedure, exposure of the diene 12
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Two such reagents, easily prepared
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The enantiomerically-pure imine 2 w
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Addition of 2-propenyl lithium to t
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The synthesis of 1 started with two
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ing system of vindoline, appropriat
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An additional stereogenic center is
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60. Synthesis of the Potent FBBP12
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The enantiomerically-pure fragments
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Ullman coupling of 3 with the aryl
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Sordaricin (2) is the aglycone of s
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The alcohol 5 was the common interm
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Overall, this elegant synthesis is
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3:1 mixture. That 1 was the major d
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The enantiomerically-pure intermedi
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Deprotection and acid-catalyzed cyc
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72. Total Synthesis of (±)-Sordari
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The ester 2 has a trans 6-5 ring fu
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The enantioselective Cu-catalyzed c
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77. Catalytic Asymmetric Synthesis
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Three-carbon ring expansion was car
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80. Synthesis of (-)-Strychnine The
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The enantiomerically-pure aldehyde
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83. Synthesis of (+)-Phomactin A Th
Page 127 and 128:
The transient 5-9-5 ketone 8 has tw
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86. Total Synthesis of the Galbulim
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Total Synthesis Highlights

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