Flavanones synthesis

This flavanone synthesis is well documented (B-75MI22400) and no routine examples are given here. 

Scheme 2.8 Coumarin and flavanone synthesis using L-Pro as catalyst.

Dduzorme has reported a simple synthesis of flavanones by radical denitratiQn and dehalo-genadon of 3-chlQrQ-2,3-dihydrQ-3-nitrQ-2-aryl-4//-l-ben2Qpyran-4-ones, which are readily prepared by the reacdon of salicylaldehydes with l-chlQrQ-l-nltrQ-2-arylethenes fEq. 7.73. ... 

Fig. 5 Scheme of the flavonoid pathway leading to synthesis of proanthocyanidins. The enzymes involved in the pathway are shown as follows CHS = chalcone synthase CHI = chalcone isomerase F3H = flavanone-3B-hydroxylase DFR = dihydroflavonol-4-reductase LDOX = leucoanthocynidin dioxygenase LAR = leucoanthocyanidin reductase ANR = anthocyanidin reductase adapted from [27] and [28]... 

M. T. Drexler, M. D. and Amiridis, Heterogeneous Synthesis of Flavanone over MgO, Chemical Industries (Dekker) Catal. Org. React.) 451-457 (2000). 

Figure 3.6. Synthesis of chalcone, flavanone, and stilbene from p-coumaric and malonic acids.

KREUZALER, F., HAHLBROCK, K., Enzymic synthesis of an aromatic ring from acetate units partial purification and some properties of flavanone synthase from cell-suspension cultures of Petroselinum hortense, Eur. J. Biochem., 1975, 56, 205-213. 

The stereospecific cyclization of chalcones to (2S)-flavanones is a prerequisite for the synthesis of the majority of fiavonoid subclasses derived from this branch point metabolite. This reaction is catalyzed by chalcone isomerase (CHI, CFI EC 5.5.1.6). CHI exists in two forms, one that accepts only 6 -hydroxychalcones and another that accepts both 6 -hydroxy-(naringenin chalcone) and 6 -deoxychalcones (isoliquirgentin), the latter generally found in legumes. Although 6 -hydroxychalcones will spontaneously convert to a racemic flavanone mixture, the CHI-catalyzed reaction proceeds at a rate 36 million-fold faster and is highly stereoselective for the formation of (25)-flavanones [60]. Spontaneous isomerization of 6 -deoxychalcones does not substantially occur without enzyme catalysis. 

Citrus species are well-known for their accumulation of flavone- and flavanone-glycosides, and thus should contain all of the enzyme activities necessary for the synthesis of these compounds. Two tentative consensus sequences for FNS-II have been identified by in silico analysis of the CitEST database, apparently representing the first identification of putative FNS-II genes in this genus [29]. Biochemical determination of function and analysis of the proteins encoded by these genes will be an important step toward elucidating flavone synthesis in Citrus. 

Hypervalent iodine reagents have shown promising applications in the synthesis of flavonoids. Such an example has been covered in Section II,E (Scheme 60). This section deals with various conversions from flavanone substrates. 

It has been suggested that the synthesis of flavones, flavanones, and flavonols could have evolved primarily as chemical messengers, such as defense molecules. Indeed, flavonoids have recently been described as a novel class of hormones. Interestingly, in this regard, the... 

Since the early contributions of Willstatter and Robinson, several alternative approaches following mainly two routes have been considered for synthesis of anthocyanins.One of the routes includes condensation reactions of 2-hydroxybenzaldehydes with acetophenones, while the other uses transformations of anthocyanidin-related compounds like flavonols, flavanones, and dihydroflavonols to yield flavylium salts. The urge for plausible sequences of biosynthetic significance has sometimes motivated this latter approach. In the period of this review, new synthetically approaches in the field have also predominantly been following the same general routes however, some new features have been shown in synthesis of pyranoanthocyanidins. 

The probutinidins (see Section 11.2) represent a second class of proanthocyanidins with flavan chain-extension units. Only five members of this class of compounds have been identified (Table 11.14). Their structures and absolute configurations were also confirmed by synthesis via reduction of the flavanone, butin, followed by acid-catalyzed condensation with the appropriate flavan-3-ol. A notable feature of the synthetic studies was the apparent preference for (4 8) bond formation reported by both groups of authors. 

There is little doubt, however, that the carbonyl compound which has been used most with o-hydroxyacetophenone in chromanone synthesis is benzaldehyde. This gives rise to a chalcone which cyclizes in acid or basic media to a flavanone (Scheme 227) (70JOC2286). During the acid-promoted cyclization of 5-acetamidochalcones, concomitant deacetylation occurs and 6-aminoflavanones result (56JOC1408). 

Drexler, M. T. and Amiridis, M. D. Kinetic investigation of the heterogeneous synthesis of flavanone over MgO, Catal. Lett., 2002, 79, 175-181. 

---