Furan moieties

NitrofuraZone. 2-[5-Nitro-2-furanyl)methylene]hydrazinecarboximide, the first nitrofiiran to be employed clinically, is prepared from 5-nitro-2-furancarboxaldehyde and semicarbazide (19). This product has seen clinical use topically as an antibacterial, for systemic appHcation for bacterial infections in poultry and swine, and also has been employed as a food additive. In rats, nitrofurazone is hydroxylated at the 4 position of the furan moiety (27). The involvement of nitrenium ions has also been postulated in the mechanism of action of nitrofurazone (38). 

Bromination of 4//-furo[3,2-b]indole (50) occurred at the 2-position and was assisted by prior N-benzylation with the 4-benzoyl compound a 61% yield of the 2-bromo derivative was obtained. Thus, a-attack in the furan moiety predominates (78JHC123). When the pyrazolofuran (51) was treated with one molar equivalent of bromine, a mixture of the 2-bromo... 

The potential of these transformations has not been fully exploited. The method is certainly valuable both for the purpose of studying the structure of furan polymers which might be of interest but cannot be prepared easily by conventional techniques and for preparing polymers in which a certain proportion of the hydroxyl groups of poly(vinylalcohol) are substituted with a furan moiety which gives the new product some special property. 

The final example in this section is the synthesis of a tristetrahydrofuran 2-606 described by the group of Rychnovsky [313]. Here, the tris(sulfate) 2-605 was converted into 2-606 by simply heating it in a mixture of MeCN and H20 (Scheme 2.138). The domino reaction is most likely initiated by deprotection of the primary alcohol, which then attacks the adjacent sulfonate unit in a SN2-type manner to afford the first furan moiety. Under the reaction conditions the formed acyclic sulfate is hydrolyzed affording a free secondary alcohol which then attacks the next adjacent cyclic sulfate unit. Overall, the SN2/hydrolyzation sequence proceeds three times to finally provide the poly(tetrahydrofuran) 2-606 as a single isomer in 93 % yield. 

Three pro-inflammatory steryl esters of furan fatty acids (11-13) have recently been isolated from the Mediterranean sponge Dictyonella incisa [30]. The furan moiety was clearly established by H and 13C NMR signals corresponding to... 

Oxygen-free reactions of psoralens, when in close proximity to the target, proceed via the first excited states in which the 3,4-and the 4, 5 7r-bonds of the pyrone and furan moieties, respectively, can undergo C4-cyclization reactions with, e.g., unsaturated bonds of lipids, or the C5=C6 double bonds of thymine in DNA. In reactions with DNA the psoralen is believed to intercalate with DNA in the dark. Subsequent irradiation at 400 nm usually leads to furan-side 4, 5 -monoadduct formation, whereas irradiation at 350 nm increases the formation of crosslinks in which the furan and pyrone rings form C4 cycloadducts to thymines on opposite strands [95], Subsequent irradiation of the 4, 5 -monoadducts at 350 nm leads to formation of crosslinks and conversion into pyrone-side 3,4-monoadducts. Shorter wave-... 

The furan moiety is found in many drug molecules and natural products. Examples of enzyme inadivation include the CYP1A2 inactivation by furafylline [36] and the CYP2A6 inactivation by menthofuran (see Scheme 11.2) [42],... 

Copolymers with pendant furan moieties have been used to synthesize new polymer structures by exploiting the reactivity of this heterocycle toward various dienophiles117, e.g. [60]fullerene112b. 

Intramolecular Diels—Alder reactions without prior 1,4-addition of oxygen (cf. previous section) have similarly been postulated for a number of [2.2]paracyclophane analogs. When [2](2,5)furano[2](l,4)naphthalen-ophane (42) is heated in excess dimethyl acetylenedicarboxylate at 100 °C, a polycyclic compound of structure 134 is formed. The mechanism of formation of 134 is most probably as follows 101> the furan moiety reacts as active diene component in an intermolecular Diels—Alder reaction to give 135. This is followed by further intramolecular 1,4-addition with the unsubstituted naphthalene ring as diene component to give the product 133, which has been isolated. 

Recent work on the synthesis, structure and some properties of macromolecules bearing furan rings is discussed. Two basic sources of monomers are considered, viz. furfural for monomers apt to undergo chain polymerization and hydroxymethylfurfural for monomers suitable for step polymerization.Within the first context, free radical, catiomc and anionic systems are reviewed and the peculiarities arising from the presence of furan moieties in the monomer and/or the polymer examined in detail. As for the second context, the polymers considered are polyesters, polyethers, polyamides and polyurethanes. Finally, the chemical modification of aU these oligomers, polymers and copolymers is envisaged on the basis of the unique reactivity of the furan heterocycle. 

Two polyamides bearing only furanic moieties were prepared, as shown by the following structures ... 

It was found that whereas 2-fuiyl isocyanate 29 and its difunctional 2,5-homologue 30 are unstable and resinify on standing at room temperature even if kept under nitrogen, the corresponding urethanes formed with aliphatic and furanic alcohols are stable. In more general terms, both the kinetics and the mechanism of the formation of furanic urethanes and diurethanes could be rationalized on the basis of established criteria combined with the specific effects of the furan moiety (35). All the products were M y characterized and... 

An example of the second type of modification is the application of the Diels-Alder cycloaddition reaction to polders and copol ers containing pendant or backbone furan moieties. The use of bis-dienophiles such as propiolic acid and its esters or bis-maleimides provides a means of crosslinking based on multiple bridging by the double interchain lycloadditions. The thermal reversibility of these reactions allows the return to the original linear structure (thermoplastic material) by simply heating the gel. 

Fig. 4. Protein contact surface representation of the beta-catenin/Tcf4 protein compiex interface near Tcf4 (D16). The QSURF coior-coded surface highiight two protein micro-cavities that anchor the ligand PNU-74654 at two opposite sites orange dot circle) involving a methyl-furan moiety and a benzene ring.

Friedrichsen and co-workers (135), along with Padwa, has utilized the carbonyl ylide cycloaddition to generate reactive furan moieties that can be further used in inter- or intramolecular Diels-Alder reactions to prepare aza- and carbocyclic compounds. Friedrichsen conducted a number of synthetic and theoretical studies on the reactivity, regioselectivity, and stereoselectivity of substituted furan formation and subsequent Diels-Alder reaction (Scheme 4.69). 

Tethering an iodobenzene and a furane moiety through a y0-lactam led to the formation of a unique tetracyclic y0-lactam derivative (5.17.). Oxidative addition followed by the carbopalladation of the furane ring resulted in the closure of the seven membered core in a so called heteroaryl Heck reaction "... 

Hydrolase-catalyzed domino reactions incorporating a resolution and a subsequent cycloaddition reaction have been described [95-97]. This constitutes an attractive approach to complex synthetic intermediates. For example, the l-(3-methyl-2-furyl)]propanol roc-93 reacts with ethoxyvinyl methyl fumarate (94) catalyzed by Lipase LIP (from Pseudomonas aeruginosa) to furnish a dienophilic fumarate ester, which spontaneously undergoes an intramolecular Diels-Alder reaction with the furan moiety furnishing exclusively the syn-adduct, the oxabicy-clohexene 95 in excellent along with the remaining alcohol S-96 (Scheme 4.31) [95]. A similar approach has been used for a procedure that includes a series of domino reactions that includes dynamic kinetic resolution of the 3-vinylcyclohex-... 

It reacts rapidly with oxygen forming a white polymeric solid with trinitro-fluorenone and trinitrobenzene, very weak n-complexes were formed, which appear to be stable only in the solid phase. Tetracyanoethylene does not add at the furan moiety but reacts with the cyclooctatetraene part of the molecule to give 355. The stability of 353 is such that prolonged heating with tributylphosphine has no effect. 

A novel synthesis of the sesquiterpene ( )-cinnamodial (148) utilizes the furan ring as a latent 1,4-dialdehyde synthon (81JA3226). The triol (141) was thus oxidized to the ketofuran (142). Oxidation of the furan moiety with lead tetraacetate afforded a 90% yield of epimeric diacetates (143) which when exposed briefly to DBU gave dienone (144). Epoxidation of (144) and exposure of the epoxide (145) to p-toluenesulfonic acid gave the bis-acetal (146). Reduction of this intermediate to a diol and hydrolysis of the bis-acetal furnished dialdehyde (147). Acetylation of the secondary hydroxyl group completed the synthesis of cinnamodial (Scheme 32). 

The theoretical study of thicno[3,4-z/ thiepine 15 and furo[3,4-rf thiepine 16, as dienes in thiophene or furan moieties, respectively, in the Diels-Alder reaction was investigated with semi-empirical AMI calculations <1995JHC1499>. S-Methylation at the thiophene moiety of thieno[3,4-t/]thiepine 15 was predicted to lower the activation energy and facilitate reaction with less reactive dienophiles, such as ethylene. 

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