Synthesis, X-Ray Crystal Structure and Tubulin- Binding Properties of a Benzofuran Analogue of the Potent Cytotoxic Agent Combretastatin A4

Abstract

The benzofuran (4), a ring-fused analogue of the potent antimitotic agent combretastatin A4 (1), has been prepared by a convergent route involving 5-endo-dig iodocyclization of o-hydroxytolan (5) as the key step. Compound (4), which has been characterized crystallographically as well as spectroscopically, is inactive as a tubulin-binding agent.

Palladium-Catalyzed Alkynylation of Aryl and Hetaryl Halides: A Journey from Conventional Palladium Complexes or Salts to Palladium/Carbon

“…Thus, a more general and versatile process for the synthesis of 1,2-benzothiazines was developed by use of a coupling-iodocyclization strategy. [56][57][58][59][60][61][62][63][64] The advantages of this strategy include the possibility of further functionalization of the resulting iodo compound, something that was not often feasible by the organometallic tandem coupling-cyclization method in a single pot. Thus a variety of 4-iodo-2H-benzo[e][1,2]thiazine 1,1-dioxides 34 were prepared with high regioselectivity via a two-step process involving palladium/carbonmediated C-C coupling of o-halobenzenesulfonamides 32 with terminal alkynes (Table 17), followed by iodocyclization of the resulting o-(alk-1-ynyl)arenesulfonamides 33 in the presence of elemental iodine in acetonitrile (Table 18).…”

Zinc Aluminate (ZnAl2O4) Supported and Catalyzed Highly Effective Sonogashira Cross-Coupling and Cyclization Reaction Under Microwave Irradiation Used in One-Pot Tandem Synthesis of Furo[3,2-H]Quinolines

“…[7][8][9][10][11][12][13] The Sonogashira coupling processes originally required the utilization of palladium-phosphine complexes and a CuI cocatalyst in organic solvents with phosphine or amine base. [14][15][16][17][18][19] Organic chemists are increasingly interested in new diverse and economical methods for synthesizing heterocyclic and carbocyclic [20][21][22][23][24][25][26][27][28][29] systems in a single operation. Heteroannulation of acetylenic substances with tethered nucleophilic substituents is used to assemble many flexible building pieces.…”

Molecular Iodine-Mediated Cyclization of Tethered Heteroatom-Containing Alkenyl or Alkynyl Systems

“…In recent years, molecular iodine has received considerable attention as an inexpensive, non-toxic, readily available reagent to effect iodocyclization and cyclodehydroiodination reactions of tethered heteroatom-containing alkenyl or alkynyl systems to afford heterocyclic compounds with many synthetic and biological applications. For example, iodine-promoted cyclization of tethered heteroatom (oxygen-, nitrogen- or sulfur-)-containing alkynes has proven to be an effective method for the synthesis of furans [ 1 , 2 , 3 ], pyrroles [ 4 , 5 ], thiophenes [ 6 , 7 ] indoles [ 8 , 9 ], benzo[ b ]furans [ 10 , 11 ], and benzo[ b ]thiophenes [ 12 , 13 , 14 ]. The pyrrole moiety is widely distributed in a large number of naturally occurring compounds which display a variety of physiological properties [ 15 ] including antibacterial [ 16 ], antiviral [ 17 ], and antioxidant activities and also inhibit cytokine-mediated diseases [ 18 , 19 ].…”