Total Synthesis Highlights

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pentacyclic triterpenes, including, inter alia, germanicol, α-amyrin, β-amyrin and taraxasterol (14). D. F. Taber, Org. Chem. Highlights 2010, April 5. URL: http://www.organic-chemistry.org/Highlights/2010/05April.shtm 14. The Trost Synthesis of (-)-Pseudolaric Acid B (-)-Pseudolaric Acid B (3), isolated from the bark of the golden larch Pseudolarix kaempferi, shows potent antifungal activity. A key step in the total synthesis of 3 described (J. Am. Chem. Soc. 2008, 130, 16424. ) by Barry M. Trost of Stanford University was the free radical cyclization of 1 that established the angular ester and the trans ring fusion of 2 and thus of 3. To prepare the bicyclic skeleton of 1, the authors envisioned the Rh-mediated intramolecular addition of the alkyne of 11 to the alkenyl cyclopropane. The acyclic centers of 11 were established by Noyori hydrogenation of (equilibrating) racemic 4. One enantiomer reduced much more quickly than did the other, leading to 5. The absolute configuration of the cyclopropane was set by Charette cyclopropanation of the monosilyl ether of the inexpensive diol 8. The two components were then coupled using a Corey-Schlosser protocol. Alkylation of the ylide 10 with 7 gave a new phosphonium salt, that in situ was deprotonated and condensed with the aldehyde 9. The resulting betaine was deprotonated and quenched, then exposed again to base to give the trans alkene 11. It is important in this procedure to use PhLi as the base, since the alkyl lithium can displace the alkyl group on phosphorus. The product from Ru-catalyzed cyclization was the expected 1,4-diene 12. Fortunately, it was found that TBAF desilylation led to concomitant alkene migration, to give the more stable conjugated diene 13. Selective epoxidation of the more electron-rich alkene followed by exposure to strong base then delivered 14, with the requisite angular oxygenation established.
Pseudolaric Acid B (3) would be derived from cyclization of the selenocarbonate of a tertiary alcohol. In fact, however, attempted cyclization of such selenocarbonates led only to decarboxyation and reduction. Even with the selenocarbonate 1 prepared from the secondary alcohol, the cyclization to 2 required careful optimization, including using not AIBN, but azobis(dicyclohexylcarbonitrile) as the radical initiator. Acetylide addition to the ketone 15 could be effected with high diastereocontrol, but lactone construction proved elusive. Alkaline conditions led quickly to addition of the angular hydroxyl to the activated alkene in the seven-membered ring. Eventually it was found that the ester exchange catalyst 16 developed by Otera delivered 17, that could be carried on to (-)-Pseudolaric Acid B (3). D. F. Taber, Org. Chem. Highlights 2010, March 1. URL: http://www.organic-chemistry.org/Highlights/2010/01March.shtm 15. The Nakada Synthesis of (-)-FR182877 The Streptomyces metabolite (-)-FR182877 (3) binds to and stabilizes microtubules, showing the same potency of anticancer activity as Taxol. Masahisa Nakada of Waseda University assembled (Angew. Chem. Int. Ed. 2009, 48, 2580.) the hexacyclic ring system of 3 by the tandem intramolecular Diels-Alder – intramolecular hetero Diels-Alder cyclization of 1, generating seven new stereogenic centers in a single step. The construction of the pentaene substrate 1 started with the known aldehyde 4, prepared by homologation of commercial ethyl 3-methyl-4-oxocrotonate. Addition of the propionyl
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 and 6: The side chain nitrile was prepared
Page 7 and 8: Carbonylative coupling of 1 and 2 l
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: The synthesis of the aromatic porti
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
Page 59 and 60: Evans auxiliary-controlled homologa
Page 61 and 62: 39. The Clark Synthesis of Vigulari
Page 63 and 64: The preparation of 1 began with the
Page 65 and 66: The preparation of 2 began with Cu-
Page 67 and 68: With 3 in hand, what remained was a
Page 69 and 70: 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
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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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