Synthesis of the Natural Products 3-Hydroxymollugin and 3-Methoxymollugin

Abstract

3-Hydroxymollugin 2 and 3-methoxymollugin 3 are cytotoxic compounds isolated as minor compounds from Pentas longiflora and Rubia cordifolia. Syntheses of 3-hydroxymollugin 2 and 3-methoxymollugin 3 were developed starting from easily available 3-bromomollugin 6. Surprisingly, it was found that the reaction of 3-bromomollugin 6 with sodium methoxide in methanol resulted in the formation of 3-methoxymollugin 3 and the ring-contracted methyl isopropenylfuromollugin 7. A mechanism for this ring contraction is proposed on the basis of a pericyclic retro oxa-6pi ring-opening reaction. A second synthesis of 3-hydroxymollugin 2 was based on epoxidation of methyl 3-(3-methylbut-2-enyl)-1,4-naphthoquinone-2-carboxylate 17 and subsequent reduction of the quinone moiety, ring transformation, and DDQ oxidation. The latter oxidation process results in 3-hydroxymollugin 2 along with the rearranged furomollugin 4, which is a ring-contracted analogue of the natural product mollugin 1.

Copper- versus palladium-catalyzed aromatization of 2-(methoxycarbonyl) tetralones: synthesis of methyl 1-hydroxy-2-naphthoates

“…3 This 1-hydroxy-2-naphthoate unit is present in natural products such the cytotoxic compounds 3-hydroxymollugin (3) and 3-methoxymollugin (4). 4 In addition, these hydroxynaphthoates have been used as precursors for the synthesis of taiwanin C, 5 a epipodophyllotoxin analog, 6 α,β-sorigenin methyl ethers 7 and olivine trimethyl ether.…”

“…4 In addition, these hydroxynaphthoates have been used as precursors for the synthesis of taiwanin C, 5 a epipodophyllotoxin analog, 6 α,β-sorigenin methyl ethers 7 and olivine trimethyl ether. 8 1-Hydroxy-2-naphthoates can be synthesized by: a) reaction of isocumarins with the Reformatsky reagent, 7 b) annulations of 2-formylbenzoate thioacetals with α,β-unsaturated esters followed by hydrolysis of the thioacetals with N-chlorosuccinimide or with mercury(II) perchlorate, 9 c) a three-component reaction of an aryne precursor, β-keto sulfones and α,β-unsaturated esters, 10 d) lithiation-carbonylation of α-methoxynaphthalenes, 6 e) condensation of phthalides with α,β-unsaturated esters, 8 and f) intramolecular cyclization of aryl substituted alkenyl β-keto esters by means of phenylselenyl chloride in the presence of FeCl 3 11 or by palladium.…”

$$\hbox {Re}_{2}\hbox {O}_{7}$$ Re 2 O 7 -catalyzed formal [3 + 2] cycloaddition for diverse naphtho[1,2-b]furan-3-carboxamides and their biological evaluation

“…The structures of the synthesized compounds were confirmed by Fourier transform infrared (FT-IR) spectroscopy, 1 H nuclear magnetic resonance (NMR) spectroscopy, 13 C NMR spectroscopy, and high-resolution mass (HR-MS) spectrometry. Initially, the selective methylation of 1,4-dihydroxy-2-naphthoic acid (8) with MeI in the presence of 2.0 equivalents of NaHCO 3 in N ,N -dimethylformamide (DMF) at room temperature for 3 h gave methyl 1,4-dihydroxynaphthalene-2-carboxylate 9a in 95 % yield (Scheme 1) [47]. On the other hand, the selective phenylation of 8 with triphenyl phosphite in the presence of 0.1 equivalent trifluoromethanesulfonic acid at room temperature for 12 h produced phenyl 1,4-dihydroxynaphthalene-2-carboxylate 9b in 90 % yield [48].…”

“…Recently, H H the structure and stereochemistry of these compounds were determined by X-ray crystallography, and the total synthesis of rubioncolin B (2) was accomplished by Traner [4]. Compound 3 was isolated as a natural product from Rubia cordifolia, but its stereochemistry and relative configurations were not described in their reports [8][9][10]. Furthermore, compound 3 exhibits cytotoxic and antitumor activities and is known as rubicordifolin [11].…”

Biosynthesis of Fe, Pd, and Fe–Pd bimetallic nanoparticles and their application as recyclable catalysts for [3 + 2] cycloaddition reaction: a comparative approach

“…Moreover, the increasing concerns of the environment demand the development of eco-friendly techniques for the preparation of nanoparticles. [36][37][38][39] Among these, synthetic naphthoij1,2-b]furan-3-carboxamides and benzofuran-3-carboxamides exhibit a wide range of remarkable pharmacological properties. [22][23][24] The biosynthesis of nanoparticles was carried out using green concepts, but almost all of these studies were based only on monometallic ones.…”