Synthesis of the Calophyllum coumarins. Part 2

Abstract

Synthetic routes leading to the synthesis of the natural 4-phenyl, 4-propyl and 4-methyl coumarins isolated from Calophyllum sp. are presented. 4-Aryl or -alkyl, 8-and 6-acyl 5,7-dihydroxy coumarins were chromenylated and then methylated at the 5 or 7 positions. A 4-step hydrobromination-bromination4ouble dehydrobromination sequence converted the 2-met hylbutano yl side chain into the (E)-2-met hylbut -2-enoyl (tigloyl) group to give calophyllolide, oblongulide, their natural 4-propyl analogue and the corresponding regioisomers. Demethylation and cyclisation of the tigloyl group gave inophyllums C and E, tomentolides A and B, and calanolide D. Sodium boranuide reduction of the 2,3-dimethylchromanone ring afforded inophyllums A, B, D and P, soulattrolide, calanolides A-C, costatolide, and cordatolides A and B. The structures of calanolides C and D, oblongulide and apetatolide have been reassigned. The previously unknown stereochemistry about the 2,3-dimethylchromanone ring of tomentolides A and B has been established as trans. t Present address: calophyllolide 1 R = Ph 2 R=Pr 0 M e 0 Q O ' Y oblongulide 3 apetatolide 4 ponnalide 5 R = COCHMeEt calanone 6 R = COPh cordatolide A 17 from C. ~~r d a r~-o b l~n g u m ,~ are reported to all possess a 12P-hydroxy-lOP, 11 a-dimethyl substitution pattern about the chromane ring. Inophyllum P 18 isolated from C. inophyllum, l 4 calanolide B 19 from C. lanigerum, ' together with cordatolide B 21 from C. cordato-oblong~m,~ are reported to all possess the 12a-hydroxy-lop, 1 1 a-dimethyl substitution pattern. Soulattrolide 22 isolated from C. ~oulattri,'~ C.moonii,I6 and C. teysmannii," and costatolide 23 from C. costatum, ' and C. teysmannii,' are enantiomers of inophyllum P 18 and calanolide B 19, respectively. In addition, the derivatives 12-acetoxycalanolide A 15,12-methoxycalanolide A 16 and 12-methoxycalanolide B 20 have been isolated from C.lanigerum. Inophyllum A 24, isolated from C. inophyllum, ' * and C. moonii,16 and calanolide C 25, isolated from C. lanigerum," both have a 12~-hydroxy-lOf3,11 P-dimethyl substitution pattern about the chromane ring and are therefore the C-11 epimers of inophyllum B 13 and calanolide A 14, respectively. Inophyllum D 26, isolated from C. inophyllum, l o with the 12a-hydroxy-lop, 1 1 B-dimethyl substitution pattern, is View Article Online 37 R1 = Ph, R2=Me 38 R1 = Pr, R2 =Me 39 R 1 = M e , R 2 = M e 42 R1 =Ph, R2 = M e 43 R1 = Pr, R2 = M e \ / 0 HBr Br 38MeO yields of 6-and 8-acyl coumarins in the 4-phenyl series,26 and an alternative route was used for these compounds. 4-Phenyl-5,7-dihydroxy coumarin [prepared from Pechmann condensation of phloroglucinol (1,3,5-trihydroxybenzene) and ethyl benzoylacetate in 75% sulfuric was subjected to the Friedel-Crafts acylation/Fries rearrangement conditions previously described,28 to afford 8and 6-acyl coumarins 29 and 32 in 61% yield with an isomer ratio of ca. 7:4. Each pair of regioisomers was readily separated by fractional crystallisation or by chromatography as previously d e~c r i b e d .~~...

L-Proline as an efficient and reusable promoter for the synthesis of coumarins in ionic liquid

“…The Knoevenagel condensation has often been used to prepare substituted coumarin, one of the most important chemicals in the cosmetics, agricultural, pharmaceutical and material industries for its bioactivity and photodynamic effect (Kostova et al, 1993;Palmer and Josephs, 1995;Mitra et al, 1998;Wang et al, 2002). Highly efficient reactions have been reported, involving the condensation of salicylaldehydes with malonates in the presence of piperidine under microwave conditions (Bogdal, 1998), and the use of montmorillonite KSF (Bigi et al, 1999) which requires high temperature and long reaction time (100 °C, 24 h).…”

Neoflavones. 2. Methods for Synthesizing and Modifying 4-Arylcoumarins

“…Mammea A/BB cyclo D (ponnalide) (69, R = CHMeCH 2 Me) and mammea A/AB cyclo D (MAB 5) (68, R = CHMeCH 2 Me) were prepared by condensation of the corresponding 8-acylcoumarins and 1,1-dimethoxy-3-methylbutan-3-ol in dry pyridine [52,145].…”

A Solvent-Free Synthesis of Coumarins Using Phosphotungstic Acid as Catalyst

“…They are widely used as additives in food, perfumes, agrochemicals, cosmetics, pharmaceuticals [8] and in the preparations of insecticides, optical brightening agents, dispersed fluorescent and tunable laser dye [9]. Coumarin and its derivatives have varied bioactivitives such as antimicrobial [10], antithrombotics [11], anticoagulants, antipsoriasis activity [12], anticancer [13], anti-HIV [14], antioxidant activity, antiproliferative activity [15], inhibitory activity on viral proteases [16], estrogen-like effects [17] and central nervous system modulating activities [18]. Coumarins also act as intermediates for the synthesis of furocoumarins, chromenes, coumarones and 2-acylresorcinols [19].…”