Inophyllums

Illimaquinone, such as avarone and avarol isolated from a Red Sea sponge, i.e., Smenospongia, has been reported to inhibit the RNase H activity associated with the HIV-1 reverse transcriptase at a concentration of 5 to 10 pg/rnl, whereas it was not active against the RNA-dependent DNA polymerase (RDDP) and DNA-dependent DNA polymerase (DDDP) activities of the enzyme at a concentration of 50 pg/rnl. 

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Yet other compounds have been found to inhibit HIV-1 replication through a specific interaction with HIV-1 RT (i.e., quinoxaline S-2720 [68], 5-chloro-3-(phenylsulfonyl)indole-2-carboxamide [69], dihydrothiazolo-isoindolones [70] and a number of natural substances (e.g., calanolide A and inophyllums, from the tropical rain forest trees Calophyllum lanigerum and Calophyllum inophyllum, respectively) [71,72]. All these and yet other compounds could be considered to be NNRTIs. The most potent among the NNRTIs, some of the HEPT derivatives (E-EBU-dM) [63] and a-... 

Caranfa MJ, Breen AL, Bartus HR, Johnson RK, Hertzberg RP, Westley JW. The inophyllums, novel inhibitors of HIV-1 reverse transcriptase isolated from the Malaysian tree, Calophyllum inophyllum Linn. J Med Chem 1993 36 4131-4138. 

Tropical rainforest tree and Malaysian tree A number of natural products have been reported to interact with reverse transcriptase, i.e., baicalin, avarol, avarone, psycho-trine, phloroglucinol derivatives and, in particular, calanolides (from the tropical rainforest tree, Calophyllum lanigerum) and inophyllums (from the Malaysian tree, Calophyllum inophyllum). 

Roush WR, Hall SE (1981) Studies on the total synthesis of chlorothricol-ide stereochemical aspects of the intramolecular Diels-Alder reactions of methyl undeca-2,8,10-trienoates. J Am Chem Soc 103 5200-5211 Rudler H, Denise B, Xu Y, Parlier A, Vaissermann J (2005) Bis(trimethylsilyl)-ketene acetals as C,0-dinucleophiles one-pot formation of polycyclic y-and 8-lactones from pyridines and pyrazines. Eur J Org Chem 3724-2744 Sekino E, Kumamoto T, Tanaka T, Ikeda T, Ishikawa T (2004) Concise synthesis of anti-HIV-1 Active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-michael addition. J Org Chem 69 2760-2767... 

Pyranocoumarins (C50 Phe pyran-2-one) include a variety of angular and linear compounds. A number of angular pyranocoumarins are spasmolytic and vasodilatory, notably the Ca2+ channel blocker visnadin. The inophyllums B and P from Calophyllum ionophyllum (Guttiferae) are inhibitors of HIV-1 reverse transcriptase. 

Inophyllum B (3), which is isolated from the C. inophyllum in 1972, has a similar skeleton of ( )-calanolide A with a phenyl group at the C4 position instead of the n-propyl group. 

Palmer and Josephs" reported on a general method for preparation of ( )-calano-lide A, ( )-inophyllum B, and ( )-cordatolide A as shown in Scheme 8-6. 

The total synthesis of (+)-calanolide A (1) was carried out by application of the synthetic method for (+)-inophyllum B (3) using the same strategy. 

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... 

Kawazu, K. Ohigashi, H. Mitsui, T. The piscicidal constituents of Calophyllum Inophyllum Linn. Tetrahedron Lett., 1968, 19 2383-2385. 

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