Characterization, Synthesis and Self‐Aggregation of (−)‐Alternarlactam: A New Fungal Cytotoxin with Cyclopentenone and Isoquinolinone Scaffolds

Abstract

(-)-Alternarlactam [(-)-1], a new promising cytotoxin against two human cancer cell lines, was isolated from an endophyte culture and synthesized (along with (+)-1) from readily available starting materials. The absolute configuration, chirality-activity relevance and self-aggregation of (-)-1 were assigned by a combination of synthetic, spectroscopic and computational approaches. The full characterization of the new fungal cytotoxin may provide valuable information in the discovery of new antitumor agents.

A CuBr-mediated aerobic reaction of 2-alkynylbenzaldehydes and primary amines: synthesis of 4-bromoisoquinolones

“…The substituents R 2 on the alkyne could include not only various aryl groups (for 3ba-3ja) but also several normal-and cyclo-alkyl groups (for 3ka-3ma), giving the corresponding isoquinolones 3 in good yields except for the cases of electron-deficient aryl groups (for 3ea and 3fa). On the benzene ring, several electrondonating groups (for 3na-3pa) as well as a fluorine atom (for 3qa) could be introduced as R 3 . This method could allow for incorporating heteroaryl motifs such as benzofuran (for 3ra) and pyridine (for 3sa), although the yields were moderate, and protonated isoquinolone 4sa was isolated along with 4-bromoisoquinoline 3sa from the reaction of pyridyl derivative 1s.…”

“…Among nitrogen-containing heterocycles (azaheterocycles), isoquinolones and their derivatives are a common core component of some biologically active natural alkaloids as well as potent pharmaceutical drugs. The representative examples are kibdelones A-C (and their isomeric metabolites such as cervinomycin A 2 and SCH56036), 1 fredericamycin A, 2 alternarlactam, 3 and NSC314622. 4 Based on these backgrounds, diverse synthetic approaches to construct isoquinolone frameworks have been exploited, [5][6][7][8] while there remains a need for conceptually novel and versatile methodologies for chemical synthesis of isoquinolones from readily available building blocks with selective control of the substitution patterns.…”

Structural Diversity and Biological Activities of Novel Secondary Metabolites from Endophytes

“…Compound 38 has been demonstrated to be significantly cytotoxic against the human breast cancer cell line MCF-7 and colon cancer cell line SW1116 with IC 50 values of 42.1 and 55.7 μM, respectively. (−)-Alternarlactam ( 40 , Figure 7 ), as a unique polyketide, was also described firstly by the Tan group and was obtained from a strain of Alternaria living inside the leaves of Carex aridula [ 57 ]. Compound 40 contains two important antitumor-related pharmacophores, cyclopentenone and isoquinolinone scaffolds, and was highly effective against human cervix HeLa adenocarcinoma cell and human hepatocellular carcinoma cell with IC 50 of 4.2 μM and 5.9 μM, respectively.…”

“…Compound 40 contains two important antitumor-related pharmacophores, cyclopentenone and isoquinolinone scaffolds, and was highly effective against human cervix HeLa adenocarcinoma cell and human hepatocellular carcinoma cell with IC 50 of 4.2 μM and 5.9 μM, respectively. The total synthesis of 40 has been achieved through using two commercially available chemicals, 3,5-dimethoxyaniline and (±)-4-methyl-1,2-cyclo-pentanedione [ 57 ].…”

Neuraminidase Inhibitors from marine-derived actinomycete Streptomyces seoulensis

“…In our continuing efforts to discover novel natural bioactive products from microbes associated with plants (Zhang et al . ), insects (Zhang et al . ) and marine creatures (Liu et al .…”