Total Synthesis Highlights

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was constructed by ring-closing metathesis of 1. The real challenge of the synthesis was the enantiospecific preparation of 1 from D-glucose. The starting point for the preparation of 1 was the glucose derivative 4. Selective acetonide hydrolysis followed by oxidative cleavage gave the ester 5, which on base treatment followed by hydrogenation delivered the endo ester 6. Condensation of the enolate of 6 with formaldehyde proceeded with high diastereoselectivity, to give, after protection, the ester 7. Conversion of the ester to the vinyl group, exposure to methanolic acid and ether formation completed the preparation of 9. The construction of the cyclobutane of 1 was effected by an interesting application of the Negishi reagent (Cp 2 ZrCl 2 /2 x BuLi). Complexation of Cp 2 Zr with the alkene followed by elimination generated an allylic organometallic 11, which added to the released aldehyde to give the cyclobutanes 12 and 13 in a 2.4:1 diastereomeric ratio. Homologation of the aldehyde 13 and subsequent oxidation were straightforward, but subsequent methylenation of the hindered carbonyl was not. At last, it was found that Peterson olefination worked well. Metathesis then delivered the cyclopentene 2. The last carbons of the skeleton were added by intramolecular aldol cyclization of the thioester 16.
The seemingly simple task of converting the alkene of 17 into a ketone proved challenging. Eventually, dihydroxylation followed by oxidation, and then SmI 2 reduction, completed the transformation. This still left the challenge of controlling the cyclopentane stereogenic center. Remarkably, dehydration and epimerization led to (+)-Fomannosin (3) as a single dominant diastereomer. 28. The Wood <strong>Synthesis</strong> of Welwitindolinone A Isonitrile Welwitindolinone A Isonitrile (3) is the first of a family of oxindole natural products isolated from the cyanobacteria Hapalosiphon welwischii and Westiella intricate on the basis of their activity for reversing multiple drug resistance (MDR). A key transformation in the total synthesis of 3 reported (J. Am. Chem. Soc. 2008, 130, 2087) by John L. Wood, now at Colorado State University, was the chlorination of 1, that in one step established both the axial secondary chloro substituent and the flanking chiral quaternary center. The starting material for the synthesis of 3 was the diene acetonide 5, readily prepared from the Birch reduction product 4. Intermolecular ketene cycloaddition proceeded with high regio- and diastereoselectivity, to give the bicyclooctenone 6.
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 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: eduction of 8 delivered the primary
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
Page 71 and 72: The aldehyde 1 was in fact not isol
Page 73 and 74: 47. The Nicolaou Synthesis of Plate
Page 75 and 76: The enantiomercially-pure cyclopent
Page 77 and 78: Although the tandem ring closing me
Page 79 and 80: procedure, exposure of the diene 12
Page 81 and 82: Two such reagents, easily prepared
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
Page 95 and 96:
The enantiomerically-pure fragments
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 and 122:
80. Synthesis of (-)-Strychnine The
Page 123 and 124:
The enantiomerically-pure aldehyde
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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