Total Synthesis Highlights

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One could envision reduction of the lactam carbonyl of 1 to an aldehyde equivalent, that would then, under acidic conditions, condense to form the desired aminal 2. This approach was, however, not successful. As an alternative, conditions were developed to convert 1 to the amidine 16. Reduction then proceeded with the expected high diastereocontrol, to give the cis 1,3-fused aminal 2. This was not isolated, but was directly acylated with acryloyl chloride, to 17. The synthesis of (-)-cernuine 3 was concluded by Grubbs cyclization of 17 to 3, followed again by hydrogenation. Note that there was a key difference between this cyclization and the Grubbs cyclization of 12 that led to 13, in that 17 contained a basic N, while 12 did not. For the cyclization of 12, the first generation Grubbs catalyst was sufficient, while for the cyclization of 17, the second generation catalyst was required. This synthesis illustrates the efficacy of the Grubbs cyclization for polycyclic construction. The approach outlined here also highlights the power of current methods for enantioselective allylation of imines for the construction of enantiomerically pure, and, in the context of this synthesis, diastereomerically pure, aminated secondary stereogenic centers. 28. The Roush <strong>Synthesis</strong> of (+)-Superstolide A (+)-Superstolide A (3), isolated from the New Caledonian sponge Neosiphonia superstes, shows interesting cytotoxicity against malignant cell lines at ~ 4 ng/mL concentration. The key transformation in the synthesis of 3 described (J. Am. Chem. Soc. 2008, 130, 2722. ) by William R. Roush of Scripps Florida was the transannular Diels-Alder cyclization of 2, which established, in one step with high diastereocontrol, both the cis decalin and the macrolactone of 3.
The octaene 1 was assembled from four stereodefined fragments. The first, the linchpin 6, was prepared from the stannyl aldehyde 4. Homologation gave the enyne 5, which on hydroboration and oxidation gave 6. Earlier, Professor Roush had optimized the crotylation of the protected alaninal 7. In this case, the Brown reagent 8 delivered the desired Felkin product 9. Protection followed by ozonolysis gave the aldehyde 10. Crotylation with the Roush-developed tartrate 11 then gave the alkene 12, setting the stage for conversion to the iodide 13. Coupling of 13 with 6 completed the preparation of 14. The third component of (+)-superstolide A (3), the phosphonium salt 21, was assembled by Brown allylation of the aldehyde 15, to give 17. Protecting group interchange followed by ozonolysis delivered 18, which via Still-Gennari homologation was carried on to 21. Condensation with the fourth component, the aldehyde 22, and esterification with 14 then gave 1.
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 and 40: eduction of 8 delivered the primary
Page 41 and 42: The seemingly simple task of conver
Page 43: fermentation of halogenated aromati
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
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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
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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