Pyran tetracyclic

The Heck coupling is also efficient in the formation of pyrane derivatives. By starting from the appropriately substituted 1,3,5-tribromobenzene derivative, three fused pyrane rings were constructed in the same reaction. The triple Heck reaction in the presence of palladium acetate and triphenylphosphine led to the formation of the tetracyclic product in good yield accompanied by a minor amount of the tricyclic intermediate(4.12.).13... 

The regiospecific cyclization of some glutaconic half-esters under dehydration conditions leads to 6-alkoxypyran-2-ones (82JOC1150). The reaction presumably proceeds via a carboca-tion which undergoes proton loss. The cyclic glutaconic derivative (311) gives the fused pyran-2-one (312) which has been used as precursor of various tetracyclic molecules (Scheme 89). 

Pericyclic reactions involving thiophenes have been utilized to prepare a variety of complex heterocycles. The intramolecular Diels-Alder reaction of 2-vinylbenzo[i]thiophene 92 produced a pair of tetracyclic adducts 93 and 94 <02TL3963>. Coupling of Fischer carbene 96 with 3-alkynylthiophene 95 led to the formation of thieno[2,3-c]pyran-3-one 97 in one step <02JOC4177>. An intramolecular cycloaddition of 97 then afforded tetracyclic adduct 98. A ruthenium-catalyzed cyclodimerization reaction involving bis-thienyl acetylene derivatives was... 

Cycloaddition of rhodium carbenoids across the pyran double bond is not observed with photochromic naphthopyrans. Rather, naphtho[2,l-i]pyrans are attacked at the electron-rich 8-position to give 24 and cycloaddition at the 5,6-bond of the naphthalene unit is accompanied by opening of the pyran ring in the case of the [1,2-6] isomer leading to 25. An intramolecular variant of this reaction yields the tetracycle 26 <04TL6151>. 

Saquayamycins A-F inhibited bovine brain FPTase with IC50 values of 1.5-2.0 ijM. Aquayamycin was the most active member of this class with an IC50 value of 1.3 /tM. The activity of the latter compound suggests that the FPTase activity is probably associated with the tetracyclic core since the pyran linkages contribute minimally to the inhibitory activity. Adriamycin, a related linear tetracyclic compound, is virtually inactive indicating that the anthracene-type bent structure is required for activity. In contrast to the paucity of data for the several compounds described earlier, mechanistic kinetic data indicate that saquayamycins were noncompetitive with respect to Ras-peptide, but surprisingly, no data was presented with respect to FPP. 

The reaction of azulenotropone 209 with sulfur ylide ethyl dimethyl-sulfuranylidene acetate (EDSA) )delds, instead of the expected homo-tropone, dihydro pyran 210 (82CL2027). This compound by hydride abstraction transforms to a cation (in 211a) or its mesomers that when neutralized yields tetracyclic pyran 212, the protonation of which regenerates the cation (in 211b). Pyran 212 is also obtained from dihydro compound 210 by treatment with DDQ and neutralization. 

Protonation of tetracyclic pyran 212 produces salt 211b (82CL2027), and solving tricyclic pyrone 70 in trifluoroacetic acid seems to afford a 13C-1271 electrons resonance system without the oxygen participating in the resonance (04BML63). 

Li et al. applied the ionic liquid l-butyl-3-methyl-l//-imidazol-3-ium bromide ([bmimJBr, 32) for the reaction of 2-hydroxy-1,4-naphthoquinone 29 with dimedone derivatives 31 and several aromatic aldehydes 30 to afford a tetracyclic 471-pyran 33 (Scheme 13.11) [18]. The ionic liquid was proven to be reusable four times, and the product 33 could be isolated in good yield (80-89%) by simple filtration/ recrystallization. 

The synthesis of a different type of tetracyclic 4//-pyran compounds 36 was reported by Shestopalov et al. (Scheme 13.12) [19]. The application of a catalytic amount of A-methylmorpholine (NMM) in a mixture of ethanol and DMF at elevated temperatures provided the desired products in short reaction times and good yields (75-88%). 

SCHEME 13.11 Synthesis of a tetracyclic 4//-pyran derivative 33 using [bmimJBr ionic liquid 32. 

Nair and coworkers [19] reported a hetero-Diels-Alder reaction of pentafulvene 36 (acting as a 2% component) with tetracyclic enone 70 (the 4jt-heterodiene), to give the polycyclic cage compound 71 containing a pyran moiety (Scheme 7.18). 

---