Synthesis and Absolute Configuration of (−)-3-Butyl-7-hydroxyphthalide, a Cytotoxic Metabolite ofPenicillium vulpinum*

Antiproliferative Role of Secondary Metabolites From Aspergillus unguis AG 1.1 (G) Isolated From Marine Macroalgae Enteromorpha sp. by Inducing Intracellular ROS Production and Mitochondrial Membrane Potential Loss Leading to Apoptosis

“…Butylidenephthalide, present in many medicinal herbs possesses various bioactivities including antitumor activity (Chang et al, 2020). A cytotoxic 3-butyl-7-hydroxyphthalide was reported from Penicillium vulpinum (Ohseki and Mori, 2003). The production of 3-butylidene-7-hydroxyphthalide has not been reported from a fungal source to the best of our knowledge.…”

Diketopiperazines and Phthalides from a Marine Derived Fungus of the Order Pleosporales

“…Analysis of chemical shift differences between S-and R-MTPA esters, (Δδ S -δ R ) (see Supporting Information) indicated that the absolute configuration at C-3′ of 2 was R. Thus, compound 2 was identified as (3S,3′R)-3-(3′hydroxybutyl)-7-methoxyphthalide (2). Surprisingly, although phthalide 3 had previously been synthesized [14], [16], [17], its 1 H-and 13 C-NMR data have never been yet reported. In the present work, we successfully assigned protons and carbons in (S)-3-butyl-7-methoxyphthalide (3), which was isolated as a natural product for the first time.…”

“…In the present work, we successfully assigned protons and carbons in (S)-3-butyl-7-methoxyphthalide (3), which was isolated as a natural product for the first time. The absolute configuration at C-3 in 3 was assumed to be S, as phthalide 3 exhibited a similar negative specific rotation to that of (S)-3-butyl-7-hydroxyphthalide, a cytotoxic metabolite of the fungus Penicillium vulpinum [14]. The isolated compounds were evaluated for their cytotoxic activity against cancer cell lines, including HepG2 (human hepatocellular liver carcinoma cell line), A549 (human lung carcinoma cell line), HCC-S102 (hepatocellular carcinoma cell line), HuCCA-1 (human cholangiocarcinoma cancer cells), KB (human epidermoid carcinoma of the mouth), HeLa (cervical adenocarcinoma cell line), MDA-MB231 (human breast cell line), T47 D (human mammary adenocarcinoma cell line), HL-60 (human promyelocytic leukemia cell line), and P388 (murine leukemia cell line).…”

Synthetic Racemate and Enantiomers of Cytosporone E, a Metabolite of an Endophytic Fungus, Show Indistinguishably Weak Antimicrobial Activity

“…In analogy with our previous synthesis of bioactive and naturally occurring phthalides, 4,5) the Snieckus's ortho lithiation methodology 6,7) was employed as the key step. Accordingly, commercially available 3,4,5-trimethoxybenzoyl chloride (2) was treated with diethylamine to give N, N-diethylamide 3.…”

“…To synthesize the enantiomers of 1, weˆrst expected that our methods for the synthesis of (R)-and (S )-3-butyl-7-hydroxyphthalide would work perfectly: 5) (i) Miyaura-Suzuki coupling (Scheme 2, 7ª8), 8) (ii) Sharpless asymmetric dihydroxylation (8ª9) 9) and (iii) Barton radical deoxygenation. 10) Our expectation concerning the high enantioselectivity of the asymmetric dihydroxylation turned out to be too optimistic, and weˆnally had to use the less sophisticated method of the enantiomeric separation of 12 by preparative HPLC.…”