Total Synthesis Highlights

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For strychnine 3, the ketone 11 was converted to the alkene 12 by reduction of the enol triflate derived from the more stable enolate. Deprotection and acylation gave 13, which was cyclized with Pd to give, after equilibration, the diene 14. Alkylation, to give 15, followed by Pd-mediated cyclization then gave 16, which was reduced and cyclized to (-)-strychnine 3. 81. Enantioselective Total Synthesis of (+)-Amphidinolide T1 Amphdinolide T1 1 is representative of a family of macrolides, isolated from the Amphidinium marine dinoflagellates, that show significant antitumor properties. Arun Ghosh of the University of Illinois at Chicago recently completed (J. Am. Chem. Soc. 2003, 125, 2374.) a total synthesis of 1, based conceptually on the convergent coupling of the enantiomerically-pure fragments 2 and 3. For each of the two fragments, a key component was assembled by the syn selective aldol condensation developed by Ghosh. For 2, addition to 3-benzyloxypropionaldehyde gave 4, which was carried on to the protected lactol 6. Homologation to 7 allowed Grubbs coupling with the fragment 8, leading to 9. Activation of the lactol by condensation with benzenesulfinic acid then gave 2.
The enantiomerically-pure aldehyde 14was prepared by adding dithiane to the commercially-available glycidyl tosylate 10. For the other half of 3, another syn-selective aldol condensation gave 12, which was carried on to the iodide 13. Reduction with t-butyl lithium, addition of the resulting organolithium to 11 and oxidation then gave the coupled ketone, which was homologated using the Petasis procedure to give 14. In fact, the sensitive disubstituted alkene of 14 turned out to not be stable to the subsequent AlCl 3 coupling conditions, so the alkene and the secondary alcohol were protected together as the bromoether 15. Condensation of the derived enol ether 16 with the sulfone 2 in the presence of DTBMP (2,6-di-t-butyl-4-methylpyridine) then gave 17. Yamaguchi lactonization followed by regeneration of the alkene by zinc reduction completed the synthesis of 1. 82. Synthesis of (+)-4,5-Deoxyneodolabelline The dolabellanes, represented by 3-hydroxydolabella-4(16), 7, 11(12)-triene-3,13-dione 1 and the neodolabellanes, represented by (+)-4,5-deoxyneodolabelline 2, are isolated from both terrestrial and marine sources. They show cytotoxic, antibiotic and antiviral activity. The recent synthesis of (+)-4,5-deoxyneodolabelline 2 by David Williams of Indiana University (J. Am. Chem. Soc., 2003, 125, 1843.) highlights both the strengths and the challenges of the current state of the art in asymmetric synthesis.
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近年来完成的天然产
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The starting point for the synthesi
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The side chain nitrile was prepared
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Carbonylative coupling of 1 and 2 l
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6. The Overman Synthesis of Briarel
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There were two remaining problems i
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The iodide 19 was enantiomerically
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To complete the synthesis of 3, it
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The assembly of 2 began with the li
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The synthesis of the aromatic porti
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Pseudolaric Acid B (3) would be der
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Reduction of the ketone then set th
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The absolute configuration of 1 was
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The keto phosphonate 16 for the las
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Nakamura reagent delivered the ally
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21. The Overman Syntheses of Nankak
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The benzyloxy aldehyde 1 was prepar
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Debenzylation of 11 followed by ace
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The Hoveyda Synthesis of (-)-Clavir
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eduction of 8 delivered the primary
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The seemingly simple task of conver
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fermentation of halogenated aromati
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The octaene 1 was assembled from fo
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The starting point for the preparat
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Several aspects of this synthesis a
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To achieve the syn relative (and ab
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The diol 6 is C 2 -symmetrical, but
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The last challenge was the establis
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(+)-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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Page 73 and 74: 47. The Nicolaou Synthesis of Plate
Page 75 and 76: The enantiomercially-pure cyclopent
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Page 79 and 80: procedure, exposure of the diene 12
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Page 83 and 84: The enantiomerically-pure imine 2 w
Page 85 and 86: Addition of 2-propenyl lithium to t
Page 87 and 88: The synthesis of 1 started with two
Page 89 and 90: ing system of vindoline, appropriat
Page 91 and 92: An additional stereogenic center is
Page 93 and 94: 60. Synthesis of the Potent FBBP12
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Page 97 and 98: Ullman coupling of 3 with the aryl
Page 99 and 100: Sordaricin (2) is the aglycone of s
Page 101 and 102: The alcohol 5 was the common interm
Page 103 and 104: Overall, this elegant synthesis is
Page 105 and 106: 3:1 mixture. That 1 was the major d
Page 107 and 108: The enantiomerically-pure intermedi
Page 109 and 110: Deprotection and acid-catalyzed cyc
Page 111 and 112: 72. Total Synthesis of (±)-Sordari
Page 113 and 114: The ester 2 has a trans 6-5 ring fu
Page 115 and 116: The enantioselective Cu-catalyzed c
Page 117 and 118: 77. Catalytic Asymmetric Synthesis
Page 119 and 120: Three-carbon ring expansion was car
Page 121: 80. Synthesis of (-)-Strychnine The
Page 125 and 126: 83. Synthesis of (+)-Phomactin A Th
Page 127 and 128: The transient 5-9-5 ketone 8 has tw
Page 129: 86. Total Synthesis of the Galbulim
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Total Synthesis Highlights

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