Chromanone ring

Chenara et al." was the first research group to establish the racemic calanolide A ( 1) in 1993 (Scheme 8-1) and the related (zb)-calanolide C and D via a five-step synthesis with 15% overall yield starting from phlorglucinol and then constructed the coumarin (A, B rings) followed by the chromanone ring (C) using a Lewis... 

The (—)-quinine-catalyzed IMA of 40 gave cw-(- -)-methoxy chromanone cou-marin (cA-41) in 67% yield with 98% ee and its trans-41 in 21% yield with lower eantioselectivity (39% ee). The Mgl2-assisted isomerization of cis-(+)-41 accompanied by demethylation followed by the reaction of the formed diastereomeric mixture of chromanone 42 (without separation) with senecioyl aldehyde in the presence of phenyl boronic acid under the same condition to construct the 2,2-dimethyl chromanone ring reported in the synthesis of (+)-inophyllum B (3). The yield of trans-(+)-43 in 61% with 91% ee and its cw-isomer (+)-43 corresponded to the (+)-calanolide D as a minor product in 23% yield with 84% ee. At last, the synthesis of (+)-calanolide A (1) was accomplished by hydride reduction of (+)-43 with... 

Ishikawa, T. Oku, Y. Tanaka, T. Kumanoto, T. An approach to anti-HIV-1 active calophyllum coumarin s3mthesis An enantioselective construction of 2,3-dimethyl-4-chromanone ring by quinine-assisted intramolecular Michael-type addition. Tetrahedron Lett., 1999, 40 3777-3780. 

The precursors of flavonoid biosynthesis include shikimic acid, phenylalanine, cinnamic acid, and p-coumaric acid. Shikimic acid acts as an intermediate in the biosynthesis of aromatic acid. The basic pathways to the core isoflavonoid skeletons have been established both enzymatically and genetically [16]. The synthesis of isoflavones can be broadly divided into three main synthetic pathways the formylation of deoxybenzoins, the oxidative rearrangement of chalcones and flavanones, and the arylation of a preformed chromanone ring. In leguminous plants, the major isoflavonoids are produced via two branches of the isoflavonoid biosynthetic pathway, and the different branches share a majority of common reactions [1]. Unlike the common flavonoid compotmds, which have a 2-phenyl-benzopyrone core structure, isoflavones, such as daidzein and genistein, are 3-phenyl-benzopyrone compounds. Biochemically, the synthesis of isoflavones is an offshoot of the flavonoids biosynthesis pathway. Several attempts have aimed to increase... 

The spin density of tocopheroxyl radical 2, a classical phenoxyl radical, is mainly concentrated at oxygen 0-6, which is the major position for coupling with other C-centered radicals, leading to chromanyl ethers 5. These products are found in the typical lipid peroxidation scenarios. Also at ortho- and para-positions of the aromatic ring, the spin density is increased. At these carbon atoms, coupling with other radicals, especially O-centered ones, proceeds. Mainly the para-position (C-8a) is involved (Fig. 6.3), leading to differently 8a-substituted chromanones 6. 

The orthometallation-carbonylation sequence illustrated in Scheme 155 affords a useful regiospecific methoxycarbonylation of the aryl ring of 4-chromanones.232 Unfortunately an extra step is incurred in the synthesis because of the unreactivity of the dimeric complexes (126) toward carbonyl insertion. 

A photochemical approach to the synthesis of precocenes /, II, and III, interesting as juvenile hormome inhibitors [177,178], has been deviced starting from the phenolic esters of 3-methylcrotonic acid. This is shown in Scheme 61 for the synthesis of precocene I (235) [179] and in Scheme 62 for the synthesis of precocenes II (238) and III (239) [180]. The rate of the cyclization process leading to chromanones, like 234 or 237, has been found to depend on the stereochemistry of the double bond. Thus, ring closure is more rapid for the trans than for the cis isomer, although no clear-cut trend can be established [181],... 

F yridinium oxime 394 in the presence of concentrated EECl gives oxazepine 395 in 61% yield (eqnation 172) . Beckmann rearrangement of 4-chromanone oximes in the presence of polyphosphoric acid or diisobntylalnminium hydride also afforded substituted benzoxazepinone ring. 

For examples of Ru-catalyzed hydrogenation of N-(3.4-dihydro-2-naphthalenyl)-acetamide see (a) Renaud. J.L., Dupau, P., Hay. A.-E.. Guingouain. M., Dixneuf P.H. and Brtmeau. C. (2003) Ruthenium-catalysed enantioselective hydrogenation of trisubstituted enamides derived from 2-tetralone and 3-chromanone Influence of substitution on the amide ai m and the aromatic ring. Adv. Synth. Catal.. 345. 230-238. 

Chromanones and coumarins, compounds which contain the pyranone ring system, are known to provide plant cells with protection from UV rays. With this in mind, copolymers... 

The rings in the reduced chromanone (174) are cis- fused and the pyranone ring is chair-shaped. The axial 2-hydroxy group is intermolecularly hydrogen bonded to the carbonyl group (81JCS(P1)1096). 

A reaction which involves both ring atoms and substituent is of considerable interest because the substrate is of a naturally occurring class of compounds. 3-Arylidene-chromanones (585) or homoisoflavanones, when heated with nickel in xylene isomerize to the 3-benzylchromone (586) (74IJC281) a number of homoisoflavanones occur in the bulbs of Eucomis bicolor, for example, eucomin (585 R = OH, Ar = 4-MeOC6H4). The stereochemistry about the double bond of compound (585 R = MeO) is altered from (E) to (Z) by irradiation at 300-400 nm (8lFOR(40)l05>. 

The photochromic behaviour of the reduced xanthone (587) when irradiated has been studied. The yellow or orange colour thus produced is due to ring opening to the chromanone (588). This colour fades gradually as the reverse reaction proceeds (69JOC2407). 

Chromanone and its isomer isochroman-4-one (623) add ethyl diazoacetate at the carbonyl group and the resulting compound undergoes ring enlargement on treatment with mineral acid. The benzoxepin-4(3H)-one (624) is obtained on heating with acid (79JCR(S)142). 

Both chemical and catalytic methods are available to convert chromanones to chromans, and flavones to flavans. Clemmensen s method is the most commonly used and usually gives good yields, but diborane is sometimes preferable. The Wolff-Kishner method appears to degrade the pyran ring and is rarely used on chromanones. The conditions of catalytic reduction have to be rather more drastic in order to produce chromans and flavans but much depends on the activity of the catalyst and on the solvent used. If the chromanol is first formed, more severe conditions are usually required to complete the reduction (77HC(31)207>. 

The benzene ring of fused dihydropyrans is more easily attacked by electrophiles than that of the corresponding pyran. However, the activating effect of the carbonyl group on the 3-position of chromanones and flavanones ensures that halogenation normally occurs at that position preferentially. Thus, 3-mono- and 3,3-di-bromination is readily achieved with appropriate molar proportions of bromine but bromination of 2,3-dihydronaphtho[2,l-Z>]pyran-l-one (675) in acetic acid gave the 7-bromo derivative (676) (48JA599). 

Nitro groups attached to the benzene ring of chromans or chromanones may be reduced catalytically to give the amines but 3-aminochromanones (698) are usually obtained from the oxime (697) of the chromanone by the Neber rearrangement. The free bases are rather unstable (69JMC277). 

The usual range of solvents associated with Friedel-Crafts reactions is available carbon disulfide and nitrobenzene have found frequent use. The choice of solvent may influence the extent of cyclization. Thus, in ether, 1,2,3,5-tetramethoxybenzene yielded the uncyclized product with 3,3-dimethylacryloyl chloride, whereas in a mixture of ether and tetrachloroethane the major product was the chromanone. This example is also of interest since ring closure could involve either the 2- or 6-methoxy group. In fact, the formation of the 5,6,7-trimethoxy isomer was not observed. The identity of the product was established by conventional 14C labelling (60BSB593). 

Figure 21.10 Plot of log k, where k is the first-order rate contant, versus pH for the ring opening of 8a-hydroxy-2,2,5,7,8-pentamethyl-6-chromanone (IHb) at zero ionic strength and zero buffer concentration. [From Ref. 6, reprinted with permission.]...

An analogous ring cleavage has been reported in 6,6-dimethyl-dibenzo[M]pyran.20 A more complex sequence of reactions has been observed for 4-carbomethoxy-3-chromanone (23) and the proposed pathway is outlined in Scheme 1 21 1,5-Hydrogen migration occurs readily in the... 

Another example of an equilibrium involving ring-formation is the cyclization of 2-hydroxychalcones (12) to form chromanones (8 b). The... 

The chromanone oxime 195 is carbonylated in the aromatic ring to give the ester... 

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