(+)-quadrone

The determination of the absolute configurations (ACs) of chiral molecules using the chiroptical techniques of optical rotation (OR), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) has been revolutionized by the development of density functional theory (DFT) methods for the prediction of these properties. Here, we demonstrate the significance of these advances for the stereochemical characterization of natural products. Time-dependent DFT (TDDFT) calculations of the specific rotations, [alpha](D), of four cytotoxic natural products, quadrone (1), suberosenone (2), suberosanone (3), and suberosenol A acetate (4), are used to assign their ACs. TDDFT calculations of the ECD of 1 are used to assign its AC. The VCD spectrum of 1 is reported and also used, together with DFT calculations, to assign its AC. The ACs of 1 derived from its [alpha](D), ECD, and VCD are identical and in agreement with the AC previously determined via total synthesis. The previously undetermined ACs of 2-4, derived from their [alpha](D) values, have absolute configurations of their tricyclic cores identical to that of 1. Further studies of the ACs of these molecules using ECD and, especially, VCD are recommended to establish more definitively this finding. Our studies of the OR, ECD, and VCD of quadrone are the first to utilize DFT calculations of all three properties for the determination of the AC of a chiral natural product molecule.

A novel cyclopentenedione, asterredione (1), two new terrecyclic acid A derivatives, (+)-5(6)-dihydro-6-methoxyterrecyclic acid A (2) and (+)-5(6)-dihydro-6-hydroxyterrecyclic acid A (3), and five known compounds, (+)-terrecyclic acid A (4), (-)-quadrone (5), betulinan A (6), asterriquinone D (7), and asterriquinone C-1 (8), were isolated from Aspergillus terreus occurring in the rhizosphere of Opuntia versicolor, using bioassay-guided fractionation. Acid-catalyzed reaction of 2 under mild conditions afforded 4, whereas under harsh conditions 2 yielded 5 and (-)-isoquadrone (9). Catalytic hydrogenation and methylation of 4 afforded 5(6)-dihydro-terrecyclic acid A (10) and (+)-terrecyclic acid A methyl ester (11), respectively. The structures of 1-11 were elucidated by spectroscopic methods. All compounds were evaluated for cytotoxicity in a panel of three sentinel cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), and SF-268 (CNS glioma), and were found to be moderately active. Cell cycle analysis of 2, 4, and 5 using the NCI-H460 cell line indicated that 4 is capable of disrupting the cell cycle through an apparent arrest to progression at the G(1) and G(2)/M phases in this p53 competent cell line. A pathway for the biosynthetic origin of asterredione (1) from asterriquinone D (7) is proposed.

1,6-Dihydro-3(2H)-pyridinone, designed as a common synthon for synthesis of various natural products, was found to be easily prepared in large scale and successfully used to synthesize a variety of alkaloids such as ibogamine, quinine and tecomanine. A tricyclo[3.3.0.0(2.8)]octane was also served as a common synthon for several sesquiterpenes such as pentalenene and quadrone. Synthetic studies by using sulfinyl chirality via an intramolecular Michael addition gave the novel route to construct spiro-ketal moiety in enantiomerically pure form. By applying this method, many natural spiro-ketal compounds were asymmetrically synthesized effectively. 3-Sulfinylated 1,4-dihydropyridine, a chiral NADH model compound, reduced activated ketones such as methyl benzoylformate to give the corresponding alcohols in excellent optical yields. A kind of 3-O-substituted pyridoxal chiral model compound was useful for preparation of alpha,alpha-dialkylated alpha-amino acids by asymmetric alpha-alkylation of alpha-amino acids. 2'-O,4'-C-Bridged nucleic acid analogs, BNAs, developed as novel type of artificial nucleic acids, showed an extraordinarily high binding affinity toward single stranded RNA and double stranded DNA complements along with excellent nuclease-resistant ability. Oligonucleotides containing BNA monomer units were proved to be very useful for various biotechnologies, such as antisense and antigene methodologies.