Furanyl derivatives

The oxidation of alcohols to carbonyl compounds has been studied by several authors and a variety of methods have been used. Papers concerned vith such oxidations are illustrated (Scheme 3.26). Good results have been obtained using pyridinium chlor-ochromate (PCC) adsorbed onto silica gel for the selective oxidation of unsaturated substrates e.g. terpene [135] and furanyl derivatives [136]. Steroidal homoallylic alcohols can be converted to the corresponding 4-ene-3,6-diones using tetrapropylammo-nium per-ruthenate (TPAP) in catalytic amounts [137]. In this case, the oxidising agent is N-methyl morpholine N-oxide (NMO). 

Reaction of 56 with thiols in dichloromethane gives the analogous alkyl-thiomethyl and cycloalkylthiomethyl derivatives [e.g., treatment with ethanethiol gives A -(2-hydroxyethylthiomethyl)vinblastine (57)] (75). Compound 56 is also a useful intermediate for the preparation of N-1-furanyl derivatives. For example, treatment of 56 with furfuryl alcohol in methylene chloride in the presence of trace acid gives N -[(5-hydroxy-methyOfurfuryl]vinblastine (58). 

A similar unravelling of the heterocyclic ring occurred in intramolecular reactions with furans,79b,159 161 leading to cyclic 1,4-diacyl-1,3-butadienes (204 equation 42)159 and (205 equation 43).79b The ideal size for the tether was five, but less efficient capture of the carbenoid was also possible with six- and seven-membered rings. With the 3-furanyl derivative (206), the acid labile structure (207) was formed, which readily rearranged to p-hydroxyphenylacetaldehyde (208 Scheme 43).161... 

Intramolecular alkoxycarbonylation of 5-hydroxyalkenes allows the preparation of tetrahydro-furanyl derivatives in good yield. Starting from 3-methyl-5-hexen-2-ol (1), a mixture of 2,5-di-substituted tetrahydrofuranyl derivatives is produced, the 2,5-/ran.v-product being the major component of the reaction mixture. This result indicates that the C-3 substituent has little effect on the stereoselectivity42. 

The penicillin molecule has been the target of such molecular manipulations to improve certain aspects of its properties. Three such modifications of ampicillin are already in clinical use. One is the pivaloyloxymethyl derivative, pivampicillin, while another is a benzo-furanyl derivative, talampicillin, and a third is bacampicillin. 

B)J for which several methods have been developed. Gerlach s synthesis of 89, which is shown in Scheme 10.7, utilized precisely this approach. The synthetic precursor of 88 was 87, produced in several steps from furanyl derivative 86. Note that when two remote, reactive ends of a molecule must be brought together so reaction can occur, intermolecular processes often dominate (sec. 6.6.B) and the low yield of 87 obtained by... 

Substituted farans have been shown to be effective end-quenchers in both the TiCU- and BCls-initiated polymerization of PIBs resulting in quantitative functionalization as determined by NMR. In addition, the allylic cation formed upon functionalization was found to be an effective initiating species for the polymerization of methyl vinyl ether to form the corresponding PIB-I7-PVE by sequential monomer addition, and the concept was extended to the preparation of three-armed star block polymers. Other bis-furanyl derivatives have also been used as coupling agents for the preparation of telechelic PIBs. °... 

Figure 6 Heterocrowns (a) a furanyl derivative (b) an anthraquinone crown (c) a pyridylcrown (d) amacrocyclic polyester (e) a cyclotetralactam. "...

Furalazine, Acetylfuratrizine, Panfuran-S. Heating nitrovin in butanol or dimethylformamide at 100—130°C affords furalazine, 6-[2-(5-nitro-2-furanyl)ethenyl]-l,2,4-triazine-3-amine (34). An improved synthesis originates with 5-nitro-2-furancarboxaldehyde and acetone, proceeds through 4-(5-nitro-2-furanyl)-3-buten-2-one followed by a selenium dioxide oxidation to the pymvaldehyde hydrate, and subsequent reaction with aininoguariidine (35). Furalazine, acetylfuratrizine (36), and the A[-A/-bis(hydroxymethyl) derivative, Panfuran-S, formed from the parent compound and formaldehyde (37), are systemic antibacterial agents. 

Reaction of 2,3-dihydro-3-hydroxy-3-methyl- 240 (R = Me), or a mixture of 2,3-dihydro-3-hydroxy-3-aryl-57/-pyrido[l,2,3-dfe]-l,4-benzoxazin-5-ones 240 (R = Ar) and (8-aroylmethoxy)quinolin-2(l//)-ones 241 (R = Ar) with ethyl 2-(bromomethyl)acrylate in the presence of activated Zn and hydroquinone gave 8-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-furanyl)-methoxy]quinolin-2(l//)-ones (242) (97HCA1161). 6,7-Dihydro derivatives of 240 reacted similarly (00HCA349). 

A plausible pathway is that the aromatisation of the cyclohexadienone 92 by a proton shift is accelerated in the presence of Ac20 under formation of acetate 93. The simultaneously generated acetic acid then cleaves the acetate to form the free phenol 94 (Scheme 44). This effect was observed for the first time during studies towards the total synthesis of the lipid-alternating and anti-atherosclerotic furochromone khellin 99 [64].The furanyl carbene chromium complex 96 was supposed to react with alkoxyalkyne 95 in a benzannulation reaction to give the densely substituted benzofuran derivative 97 (Scheme 45). Upon warming the reaction mixture in tetrahydrofuran to 65 °C the reaction was completed in 4 h, but only a dimerisation product could be isolated. This... 

The reactivity of alkynylstannanes toward electrophiles is one element in the oxygen-to-carbon rearrangement of alkynylstannane derivatives of furanyl and pyranyl lactols (e.g., Equation (85)). The cleavage of the anomeric C-O bond is assisted by the Lewis acid to give an oxonium ion, which is trapped in situ by the nucleophilic stannylalkyne. The utility of this process has been demonstrated in the synthesis of the natural product muricatetrocin C, and the drug substance CMI-977.246... 

The names of AHLs listed in Table 1 are the non-IUPAC description of compounds as N-acyl derivatives of L-homoserine lactone. Alternatively, IUPAC chemical designations for the compounds can be used. These are based on the amide unit as the principal function. Thus AT-(3-oxohexanoyl)-L-homoserine lactone is named as 3-oxo-N-(tetrahydro-2-oxo-3-furanyl)hexanamide. 

Dihydro- and tetrahydrofuroisoxazoline rings were constructed by intramolecular cycloaddition of nitrile oxides or nitrones, generated from oximes . Thus, oxime 30 and sodium hypochlorite afforded furoisoxazolines 31 (equation 14). Similarly, furanyl or thienyl oximes 32 in the presence of NaOCl afforded tricyclic products 33 in 35-90% yields (equation 15). Nitrostyrenes (ArCH=CHN02) and various nucleophiles (for example, allyl mercaptan) also generated hydroximoyl chlorides which underwent similar cycloaddition leading to bicycUc tetrahydrothiophene and tetrahydrofuran derivatives ... 

A number of furans with thiol, sulphide or disulphide substitution have been reported as aroma volatiles, and these are particularly important in meat and coffee. In the early 1970s, it was shown that furans and thiophenes with a thiol group in the 3-position possess strong meat-like aromas and exceptionally low odour threshold values [50] however, it was over 15 years before such compounds were reported in meat itself In 1986,2-methyl-3-(methylthio)furan was identified in cooked beef and it was reported to have a low odour threshold value (0.05 pg/kg) and a meaty aroma at levels below 1 pg/kg [51]. Gasser and Grosch [52] identified 2-methyl-3-furanthiol and the corresponding disulphide, bis(2-methyl-3-furanyl) disulphide, as major contributors to the meaty aroma of cooked beef. The odour threshold value of this disulphide has been reported as 0.02 ng/kg, one of the lowest known threshold values [53]. Other thiols which may contribute to meaty aromas include mercaptoketones, such as 2-mercapto-pentan-3-one. 2-Furylmethanethiol (2-furfurylmercaptan) has also been found in meat, but is more likely to contribute to roasted rather than meaty aromas. Disulphides have also been found, either as symmetrical disulphides derived from two molecules of the same thiol or as mixed disulphides from two different thiols [54]. 

Other furans included methyl- 2-furfural [4], 2-acetylfuran [5], 2-propionylfuran [6], l-(2-furanyl)-2-propanone [7] and l-(-2-furanyl)-3-butanone [8]. Several alkylpyrazines were also found, with the 2,5-dimethyl [9] and 2-methy 1-5-ethyl [10] the most abundant derivatives, and some 2-acyl-l-methylpyrroles of which only the formyl [11] and acetyl [12] derivatives were conclusively identified. 

The most potent compound of the aryl diyne series (type II) was furan derivative 9 with a Ki value of 7.5 nM. An approximately tenfold decrease of potency was observed when the 1,3-substitution pattern of the head groups of 9 was replaced by 1,4-substitution to give 24 with a K, value of 80 nM. Substitution of the 2,5-furan ring in 9 by the 3,4-thiophene ring gave 25, with a twentyfold loss of tryptase inhibition activity (K, =150 nM). Replacement of the furanyl diyne template with the 1,3-substituted phenyl diyne template 29 was well tolerated (K, = 9 nM), whereas 1,4-substituted head groups resulted in a fourfold loss of activity (27, Ki = 32 nM) compared with 29. Combination of a 1,2-substituted phenyldiyne... 

Dihydro-3-(5-nitro-2-furanyl)-5//-imidazo[2,l-6]thiazolium chloride (furazolium chloride) is a topical antibacterial agent. Substituted imidazo[l,2-c]thiazole derivatives are antihypertensives, CNS stimulants, and appetite suppressants. 2H- l,3-Dithiolo[4,5-c]pyrazole-5-thiones and imidazo[5,1 -b jthiazoles are fungicidal with low toxicity to plants, animals and hum ns. 

Fig. 2. The reaction of glucose with a protein amino group to form a glycoslylated protein (Amadori product) and subsequent glucose-derived cross-link (2-furanyl-4[5]-[2-furanyl]-lH-imidazole).

Applications of furanyl anion equivalents in stereoselective manner have been increased. An example of asymmetric conjugate addition of a furanyllithium to 1-nitrocyclohexene induced by a chiral amino alcohol derivative is shown in Equation (26). The 2-trityloxymethyl group was essential for obtaining the selectivity in the product, which was used as an entry to prepare arene-fused piperidine analogs <2004JA1954>. 

As depicted in Equation (68), anodic fluorination of ethyl 3-benzo[4]furanyl acetate was applied to the synthesis of a 2,3-difluoro-2,3-dihydrobenzo[/ ]furan derivative. A 2-fluoro-3-hydroxyl derivative was also obtained as a minor product <2003SL1631>. 

Allenyl ketones can also be cross-coupled with allenoic acids to give 2,4-disubstituted furans <2002AGE1775> or with allenamides to yield 4-(3 -furanyl)-2(5//)-furanimines <2005JOC6291>. With chiral allenoic acid derivatives, 4-(3 -furanybbutenolides can be synthesized stereoselectively with complete chirality transfer (Equation 47) <2004CEJ2078>. 

Protection of hydroxyl groups. Alcohols and phenols react with 1 and tri-ethylamine to form tetrahydro-2-furanyl (THF) ethers (85-98% yield). The reaction of acids with 1 results in THF esters. These derivatives are stable to base and nucleophilic reagents they are readily removed by acid-catalyzed hydrolysis or methanolysis. One synthetic application is conversion of the ethers into alkyl bromides by reaction with triphenyphosphine dibromide (1,1247-1248), a reaction that is faster than that with the free alcohols. 

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