Complete 1 H NMR assignment of cedranolides.

Complete and unambiguous 1 H NMR chemical shift assignment of α-cedrene (2) and cedrol (9), as well as for α-pipitzol (1), isocedrol (10), and the six related compounds 3-8 has been established by iterative full spin analysis using the PERCH NMR software (PERCH Solutions Ltd., Kuopio, Finland). The total sets of coupling constants are described and correlated with the conformational equilibria of the five-membered ring of 1-10, which were calculated using the complete basis set method. Copyright © 2015 John Wiley & Sons, Ltd.

Vibrational circular dichroism discrimination of diastereomeric cedranol acetates.

The reliability of vibrational circular dichroism (VCD) spectroscopy to discriminate four diastereomeric cedranol acetates 1-4 by means of their absolute configuration is examined. The usage of CompareVOA software to quantify comparisons of the measured infrared (IR) and VCD spectra with the corresponding simulated spectra at the B3LYP/DGDZVP and B3PW91/DGDZVP levels of theory for each diastereomer enabled the B3PW91 functional to be qualified as superior to the B3LYP functional for vibrational calculations of 1-4. Analogously, a set of quantitative VCD spectra cross-comparisons of 1-4 unambiguously distinguished the diastereomers using B3PW91 and failed using B3LYP. Remarkably, quantitative IR spectra cross-comparisons of 1-4 using B3PW91 or B3LYP functionals demonstrated that the achiral spectroscopic IR technique is not able to distinguish cedranol acetate diastereomers. VCD comparisons using anisotropy g-factor values of bands in the 1550-950 cm(-1) region of the spectra were of aid to facilitate visual spectra matching for each diastereomer.

Antiproliferative activity and absolute configuration of zonaquinone acetate from the Jamaican alga Stypopodium zonale.

The chemical investigation of specimens of the Jamaican brown alga Stypopodium zonale led to the isolation of a cytotoxic compound, zonaquinone acetate (1), along with known compounds flabellinone, not previously identified in S. zonale, stypoldione, 5',7'-dihydroxy-2'-pentadecylchromone and sargaol. The structures of the metabolites were established by analysis of the spectral data including 1D and 2D NMR experiments while the stereochemistry of 1 was assessed by VCD measurements. Cytotoxic activity was reported in vitro for 1 against breast cancer and colon cancer cell lines at IC(50) values of 19.22-21.62 µM and 17.11-18.35 µM respectively, comparing favorably with standard treatments tamoxifen (17.22-17.32 µM) and fluorouracil (27.03-31.48 µM). When tested with liver cancer cells (Hep G2), no activity was observed. Weak antioxidant activity was observed with 1 but sargaol exhibited high activity.

Synthesis and anti-HIV activity of lupane and olean-18-ene derivatives. Absolute configuration of 19,20-epoxylupanes by VCD.

Lupane triterpenoids 2 and 5-12 and oleanene derivatives 13 and 14 were prepared from lupeol (1), betulin (3), and germanicol (4). They were tested for anti-HIV activity, and some structure-activity relationships were outlined. The 20-(S) absolute configuration of epoxylupenone (8) was assessed by comparison of the observed and DFT-calculated vibrational circular dichroism spectra. The CompareVOA algorithm was employed to support the C-20 configuration assignment. The 20,29 double bond in lupenone (2) and 3-epilupeol (15) was stereoselectively epoxidized to produce 20-(S)-8 and 20-(S)-16, respectively, an assignment in agreement with their X-ray diffraction structures.

Chiral recognition of diastereomeric 6-cedrols by vibrational circular dichroism.

The use of vibrational circular dichroism spectroscopy for the chiral recognition of the two epimers of 6-cedrol, tricyclic sesquiterpenes, which contains oxygen as the heaviest atom, is shown. Bands in the 1500-850 cm(-1) region of the spectra were analyzed to calculate the anisotropy factors (g), which provided the regions of maximum circular dichroism effect for each epimer.

Cascade [1,3]-sigmatropic rearrangements of ketene O,O-acetals: kinetic and DFT level mechanistic studies.

The regioisomeric alpha-cyano ketene-O,O-dialkyl acetals 2a-e and 4a-e, sequential intermediates in the diazomethane induced conversion of indole alpha-cyano-gamma-lactones 1a-e to 2-indolyl cyanomalonates 5a-e, were isolated and characterized. Formation of the steady-state intermediate cycloprop[b]indoles 3a-e was evidenced by means of NMR and confirmed by the X-ray structure of 3c, demonstrating that the formation of 5a-e from 2a-e proceeds through two consecutive and one parallel unimolecular steps, with intermediates 3a-e formed in reversible processes. Evidence that the reversible reactions proceed via [1,3]-rearrangements is presented. The steady-state kinetic approach applied to intermediate 3 allowed a minimal two consecutive step 2 --> 4--> 5 kinetic model, in which the steric bulkiness of the alkyl substituent affects strongly the associated rate constants, k(1) and k(2), inverting the rate-determining step. The solvation effects enhanced the feasibility of these skeletal rearrangements as they stabilized the transition states to a great extent. The experimental determined thermodynamic parameters and DFT calculations suggest that these cascade rearrangements occur through [1,3]-sigmatropic mechanisms, in which asynchronous bond reorganization processes via four membered pseudopericyclic transition states are highly favorable.