Synthese und Reaktionsverhalten 2′‐substituierter Isoflavone

Abstract

The protected chalcones 6 8 prepared from acetophenone and henzaldehydes rearranged to the dimethoxypropanone derivatives 9-11 in the presence of trimethyl orthoformate by T1(NO3),.3 H20. These compounds could he cyclized to the isoflavones 12-14 in high yields (Scheme 2). The conversion of these isoflavones to the corresponding isoflavanes (model compounds of the phytoalexin glabridin; see Scheme I ) was the main goal of this work. Hydrogenation of 13 and 14 gave the isoflavanes 15 and 16, respectively, and their deprotection the racemic natural product 4-O-demethylvestitoI(l7). Reduction of 13 and 14 yielded different compounds depending on the reducing agent (Scheme 3 ) . The saturated alcohols 2&23 could he obtained with NaBH, or LiBH4. They were transferred into the raccmic 9-0-demethylmedicarpin (24) and haginin D (25) under acidic conditions. The ketones 2 6 2 8 (Scheme 4) were obtained in high yields by reduction of 12-14 with DIBAH. Deprotection of 26 yielded the racemic 2Jdihydrodaidzein (29). Compounds 13 and 27 as well as 20 and 22 showed different hehaviour under reduction conditions with Li in liquid ammonia. An efficient method for the introduction of the MeOCH,O and the MeOCH2CH20CH2 protecting groups into hydroxylated benzaldehydes and acetophenones (Scheme 5 ) is described. The appropriate experimental conditions depend on the regioselectivity and on the number of the protected groups. The protected aldehydes, especially those with a protected ortho OH group, show an extraordinary ionization hehaviour in chemical-ionization mass spectrometry (isohutane; Scheme 6 ) .Einleitung. -Bei biochemischen Untersuchungen an der Ganzpflanze und an Zellkulturen von Ornithopus sativus BROT. wurde kiirzlich das Phytoalexin Glabridin [ 11 gefunden. Wir haben die Absicht, die Biosynthese dieser Verbindung abzuklaren. Eine Kurzfassung des wahrscheinlichen Biosyntheseweges findet sich im Schema 1. Nachdem bereits die ersten enzymatischen Schritte bis zur Chalconsynthase nachgewiesen wurden [ ll, war es notwendig, fur die Abklarung des weiteren Verlaufes der Biosynthese (2'-Hydroxylase, Reduktase, Prenylase, Cyclase) insbesondere iiber Weg A oder B einige postulierte Vorliiufer herzustellen und diese als Substrate fur geplante Enzymversuche einzusetzen.Die chemische Synthese von hydroxylierten Isoflavanen aus entsprechenden Isoflavonen erfolgte bisher unter Verwendung der Benzyl-Schutzgruppe [2], die hydrogenolytisch abspaltbar ist. Im Falle der Verbindungen vom Typ Phaseollinisoflavan oder Glabridin, die noch eine zusatzliche hydrierbare Doppelbindung aufweisen, versagt die Benzyl-Schutzgruppen-Technik. Es musste demzufolge eine andere geeignete Reaktionssequenz angewendet werden. Ferner sollten diese Synthesen auch zur Isotopenmarkierung vermeintlicher Vorlaufer geeignet sein.

Synthesis of Demethylxanthohumol, a New Potent Apoptosis-Inducing Agent from Hops

“…The reaction led to the monoether in position 4, and the diethers in positions 2 and 4. To obtain products with lower molecular mass and fewer NMR signals, the introduction of MOM protecting groups (1 3 2; Scheme 2) seemed to be advantageous [11]. The acid-catalyzed deprotection turned out to occur under milder reaction conditions compared to the MEM ethers.…”

Multiple hydride reduction pathways in isoflavonoids

“…The resonance contributor 10 will encourage this mode of attack. DIBAH, normally a preferential 1,2-reducer, reacts with methoxy-, benzyloxy-, MOMO- and MEMO-substituted isoflavones to give the isoflavanones in 40–93% yield [ 16 , 21 - 23 ] (Table 1 ). Our own work has shown that even unprotected hydroxy-substituted isoflavones are reduced by a large excess of DIBAH in 50–70% yield (Table 1 ).…”

“…There is no significant difference between the K- and L-Selectride ® . In the literature, there is an isolated report of the reduction of a MOM substituted isoflavone by L-Selectride ® in 40% yield (Table 2 ) [ 16 ]. Methoxy substituted isoflavones have also been reduced by sodium hydrogen telluride to give isoflavan-4-ones in 61–71% yields [ 24 ].…”

“…Full reduction at the heterocyclic ring of isoflavones by LiBH 4 or NaBH 4 leads to isoflavanols in 20–91% yield (Table 2 ), [ 16 , 25 - 28 ]except with hydroxy substituted substrates which do not react at all. Apparently the first step involves a 1,4-addition to give the isoflavanone enolate which picks up a proton from the solvent and is reduced further to the saturated alcohol.…”

“…We present here experimental details of our own results in this field together with a thorough survey of the literature. The discussion is based on the types of reduced isoflavonoid structures formed (Figure 1 ), i.e., isoflavanones 2 , cis -isoflavan-4-ols 3 , trans -isoflavan-4-ols 4 , the ring opened α-methyldeoxybenzoins 5 and 1,2-diaryl-2-propen-1-ols 6 , and isoflavenes 7 and 8 (hydride reductions do not lead to isoflavans 9 , which however are obtained by catalytic hydrogenation [ 10 , 16 , 20 ]). Incidentally, it is appropriate to point out that flavones do not undergo similar reductive metabolism in mammals as described above for isoflavones.…”